Quercetin is a naturally derived flavonoid that has received growing attention for its wide range of pharmacological activities such as strong anticancer, antimicrobial, anti-inflammatory, and antioxidant effects. Its multiple functions and natural bioactivity make it an appealing therapeutic candidate. However, the clinical use of quercetin is still limited by issues like poor water solubility, low bioavailability, fast metabolism, and difficulties in achieving targeted delivery. Recent research has aimed to overcome these challenges through innovative formulation strategies like nanoencapsulation, polymeric carriers, 3D printing, microneedle scaffolds and surface modification. These approaches improve stability, boost bioavailability, and allow for targeted therapeutic effects. Traditional theranostic systems that use nanoparticles, quantum dots, or linked biomolecules have enhanced precision medicine by merging diagnostic imaging methods, such as MRI, PET, and fluorescence, with treatment options like targeted drug delivery and photothermal therapy. Yet, these systems face issues related to biocompatibility, cost, biodegradability, and targeting precision. Platforms based on quercetin are emerging as a promising alternative to tackle these problems. Despite their potential, this area is largely uncharted, and, to our knowledge, no thorough review has focused on quercetin’s role in multifunctional theranostic systems. This review offers a systematic look at the design strategies, biomedical uses, and potential for quercetin-based theranostics. We discuss key challenges, such as achieving controlled/stimuli-responsive delivery, validation in higher animal studies, scale-up and to emphasize future directions for evolving quercetin-based platforms as next-generation nano-theranostics.

Two-dimensional materials are promising candidates for electrode modified materials in electrochemical sensing applications. This study introduces a non-enzymatic electrochemical sensor that combines tungsten disulfide (WS2) with fluorine-doped graphitic carbon nitride (F-g-C3N4) for the detection of acetaminophen (ACMP). The synthesized WS2/F-g-C3N4 microcomposite combines the two-dimensional metal dichalcogenide and the two-dimensional fluorine doped polymeric semiconductor to form the architecture of WS2 microspheres anchored on stacked F-g-C3N4 microflakes. Compared with the previously reported electrode modification materials for electrochemical detection of ACMP, the WS2/F-g-C3N4 microcomposite exhibits enhanced current response and high intrinsic sensitivity without employing any signal amplification strategy. This enhanced performance can be attributed to the synergistic combination of high conductivity, abundant catalytic sites, exceptional chemical stability, and significant effective surface area. Under optimal conditions, the WS2/F-g-C3N4/GCE displays a good analytical performance, including good linearity across two concentration ranges (0.01–253.3 & 253.3–1616.2 µM), an extremely low limit of detection (0.004 µM), and a good sensitivity (0.535 µA µM−1 cm−2). Additionally, it demonstrates good selectivity, reproducibility, repeatability, stability, and reusability for ACMP detection in the presence of various potential interferents. The WS2/F-g-C3N4/GCE is successfully applied to detect ACMP in pharmaceutical and environmental samples, achieving the recovery rates of 95.00–98.20%. This research provides an efficient and convenient approach for synthesis of 2D materials, which show great potential in electrochemical analysis.

Chemotherapy is a fundamental modality in the treatment of breast cancer (BC), employed across both early and advanced stages. Triple-negative breast cancer (TNBC), known for its aggressive behavior and propensity for metastasis, presents significant treatment challenges due to its resistance to standard chemotherapeutic approaches. Identifying molecular targets for TNBC is imperative, especially in the absence of specifically targeted drugs and given the generally poor prognosis of the disease. Although nanomedicine has substantially grown, incorporating a variety of clinical applications, challenges such as dose-limiting toxicities and limited patient response rates continue to hinder its broader application. Over the past decade, graphene quantum dots (GQDs) have emerged as a promising category of luminescent materials, characterized by their outstanding optoelectronic properties, and their highly tunable structures and surface functionalities. These attributes make GQDs ideal candidates as drug carriers, facilitating straightforward functionalization, heightened chemotherapy sensitivity, and substantial drug loading capacities. This review provides a thorough exploration of recent advancements in GQDs applied to BC, with a specific focus on TNBC. It delves into the dynamics of breast cancer, emphasizing the diagnostic and therapeutic challenges of TNBC and the innovative potential of GQDs in this context. Furthermore, it discusses various GQD-based therapeutic strategies that hold promise for enhancing outcomes in breast cancer treatment, potentially leading to transformative advancements in the management of TNBC. Additionally, this review incorporates insights from three-dimensional (3D) tumor models, offering a comprehensive perspective on GQD-mediated interventions in breast cancer therapy.

In this work, a simple and versatile chemosensor receptor TZPYZ was synthesized through the combination of thiazole with pyrazine-2-carbohydrazide, resulting in a confirmed chemical structure via various analytical techniques including FT-IR, 1H, and 13C Nuclear Magnetic Resonance Spectroscopy, as well as High-Resolution Mass Spectroscopy analysis. TZPYZ exhibits specific colorimetric and photoluminescent responses to Ag+ ions in a solvent solution consisting of DMSO and H2O (7:3, v/v). Upon addition of Ag+ ions, noticeable changes in absorption spectra occur, resulting in a visible color change from pale yellow to blue. Additionally, an enhanced emission intensity with wavelength at 523 nm, when excited at 410 nm. Notably, TZPYZ demonstrated exceptional selectivity for Ag+ ions over other metal cations, achieving a detection limit (LOD) of 10.6 × 10−9 M and 6.74 × 10−9 M and using the UV–visible & photoluminescent titration method. Interference studies indicated minimal disruption from other metal ions on emission at 523 nm, highlighting TZPYZ discerning capability for Ag+ ions. With a binding affinity of 3.622 × 10−11 M−1, TZPYZ proved effective in detecting Ag+ ions across various water samples, showcasing its practical utility. The mechanism of interaction between TZPYZ and Ag+ ions was investigated using various experimental techniques, including Job's plot, Benesi-Hildebrand investigations, 1H NMR, and HRMS analysis. Test strips coated with TZPYZ showed selective detection of Ag+ ions, indicating its potential for on-site applications. Furthermore, DFT computations provided insights into the structural and electronic properties of TZPYZ and its complex with Ag+ ions, further elucidating the binding mechanism and stability of the complex. In addition, TZPYZ demonstrated compatibility with biological systems, as fluorescence imaging tests on MCF-7 breast cancer cells confirmed both its non-cytotoxic nature and its proficiency in detecting intracellular silver ions. Based on these findings, TZPYZ is highlighted as a highly sensitive and selective chemosensor for Ag+ ions, with promising applications in environmental analysis and bioimaging.

Bioprinting is an additive manufacturing technique to build tissue/organs that mimic the correct spatial arrangement of cells and factors layer-by-layer for fabricating complex in vitro 3D tissue/disease models for drug screening studies or as regenerative medicines for therapeutic purposes. Hydrogels play a key role in bioprinting wherein they are used as bioinks—a combination of hydrogels, cells of interest with or without factors—as a building block for the bioprinting process. This chapter begins with an introduction to bioprinting, followed by three key processes involved in the bioprinting of human tissues: preprinting, printing, and postprinting. In the preprinting process, different types of hydrogel-based cross-linking chemistries, the role of sterilization, and the effects of hydrogels’ viscoelastic properties on the printability and stability of hydrogels will be discussed in detail. Strategies to evaluate the printability and the printed structures were discussed in detail in the printing process. In the postprinting stage, the evaluation of stability and mechanical properties of printed hydrogels, cell viability, and maturation of tissues in a bioreactor are discussed. Various types of hydrogels used in bioprinting are discussed in detail, with a few case studies under each one tabulated. Finally, recent advancements such as DLP, FRESH bioprinting, SLAM technique, SWIFT, and in situ bioprinting are discussed in detail, ending the chapter with future perspectives on the path ahead for 3D bioprinting technologies.

The human vascular system comprises vessels that carry blood and lymph fluid throughout the body and play a very important role in the sustenance of the physiological homeostasis. Importantly, blood vessels deliver oxygen and nutrients to various organs and in turn remove metabolic wastes from the organs. Due to the current lifestyle modifications as well as increase in geriatric population, there is an increased incidence of vascular diseases due to dysfunction of vascular systems. Auto, allo and xenografts, though clinically used, suffer from their own limitations. Tissue engineered vascular grafts are now being explored. 3D bioprinting, one such scalable, repeatable, and very accurate additive manufacturing technology has the potential to fabricate desired vascular tissues. In this chapter, a brief background on the anatomy and physiology of the vascular tissues is presented, followed by sections on 3D bioprinting and its types. The pros and cons of these methods are also elucidated. The chapter also highlights some of the key works in 4D bioprinting applications and microfluidics-based bioprinting.

Hydrogels are a three-dimensional polymer network that absorbs and retains large quantities of fluids in a liquid state. These materials exist naturally or can be made synthetically as well, tailored to suit the application of interest. Hydrogels play an important role in tissue engineering applications, especially as injectable hydrogels and as bioinks in bioprinting applications. These techniques specifically rely on the material being ejected from a large area via a small aperture that results in a shearing force acting on the material that can alter the properties of the biomaterials. The high shear stresses can also damage materials containing cells. Further, the viscoelastic properties of hydrogels play an important role in their biomedical applications, to name a few as viscosupplements for osteoarthritis treatment, dermal fillers, and ophthalmic lubricants. Hence, in the development of novel hydrogels as biomaterials, understanding material behavior under an applied shear stress is critical and aids in design and optimizing the biomaterials. Rheology is the study of how materials flow and deform and describes the relationship between force, deformation, and time. The focus of this chapter is to introduce the basics of rheological analysis and provide a framework that can act as a guide in characterizing a biomaterial using different analytical techniques involved in rheology. This chapter will also discuss the use of rheology as one of the few characterization techniques in the development of a few biomaterials 3D bioprinting.

Cardiovascular diseases are the principal cause of life threats worldwide, with a projected 17.9 million deaths each year. The current treatment modalities for CVDs, such as pharmaceuticals and surgeries, generally provide symptomatic relief. However, the regeneration of cardiac tissue is preferred currently, and intense research in this area is happening across the globe. Also, in case of extreme heart failure cases, due to an inadequate number of organ donors, there is a need for artificial hearts made in labs that are currently being explored. Hydrogels play a crucial role in tissue engineering due to their tissue-like characteristics, which help deliver cardiac protective molecules and cells to the injured area of the heart and improve cell-based therapeutic potential. These can also support the regeneration of cardiac tissue after the occurrence of cardiovascular diseases. Various hydrogels are explored in cardiac tissue engineering, including natural hydrogels, synthetic hydrogels, natural/synthetic hybrid hydrogels, and many more based on their properties. And more recently, with the advent of 3D bioprinting technology, realizing the artificial heart as a reality is much closer than ever before. The biomaterial inks and the bioinks used in 3D bioprinting are typically hydrogels: the former ones without cells and the latter ones with cells, respectively. This chapter gives a brief background on the pathophysiology and treatment modalities of CVDs. This is followed by a detailed discussion of the types of hydrogels for cardiac tissue engineering and their pros and cons. Additionally, various approaches for cardiac tissue repair via hydrogels, from stimuli-responsive systems to hydrogels for 3D bioprinting applications, are discussed in detail. This chapter finally discusses hydrogel-based various cardiac 3D tissue and disease models that are used in drug screening applications.

Organoids are the emerging miniature 3D models that recapitulate the complex cellular heterogeneity, structure, and functions of the native tissues. Organoids have gained huge interest in the development of tissue/disease models, cell therapy, drug screening, and personalized medicine. Although utilized in various applications, the conventionally fabricated organoid models still lack cellular organization. They have a limited lifespan, nutrient exchange, reproducibility, and complex protocols that restrict their translation. The development of miniature models has reached significant heights using functional biomaterials, especially hydrogel, which mimics the native extracellular matrix with tailored mechanical and chemical properties. The hydrogel has been developed through various fabrication techniques like hanging drops, nonadherent cell culture plates, scaffold-based organoids culture, 3D and 4D bioprinted organoids, and microfluidic organoids. The advanced technology thus provides a platform for researchers to develop hydrogel-based miniature organoids as clinically relevant models for future therapeutics. This chapter delves into the evolution of conventional 3D organoids and their limitations, followed by factors that need to be considered for the development of hydrogel-based organoids and their fabrication methods toward biomedical applications.

Peripheral nerve injuries are common complications in surgical and dental practices, often resulting in functional deficiencies and reduced quality of life. Current treatment choices, such as autografts, have limitations, including donor site morbidity and suboptimal outcomes. Adipose-derived stem cells (ADSCs) have shown assuring regenerative potential due to their accessibility, ease of harvesting and propagation, and multipotent properties. This review investigates the therapeutic potential of ADSCs in peripheral nerve regeneration, focusing on their use in bioengineered nerve conduits and supportive microenvironments. The analysis is constructed on published case reports, organized reviews, and clinical trials from Phase I to Phase III that investigate ADSCs in managing nerve injuries, emphasizing both peripheral and orofacial applications. The findings highlight the advantages of ADSCs in promoting nerve regeneration, including their secretion of angiogenic and neurotrophic factors, support for cellular persistence, and supplementing scaffold-based tissue repair. The regenerative capabilities of ADSCs in peripheral nerve injuries offer a novel approach to augmenting nerve repair and functional recovery. The accessibility of adipose tissue and the minimally invasive nature of ADSC harvesting further encourage its prospective application as an autologous cell source in regenerative medicine. Future research is needed to ascertain standardized protocols and optimize clinical outcomes, paving the way for ADSCs to become a mainstay in nerve regeneration.

The development of carbon dots (CDs) as a facile high luminescent sensor for the detection of heavy metal ions is gaining more attention due to their excellent optical properties and inherent non-toxic nature. Herein, we developed nitrogen-doped carbon dots (N-CDs) using a single-step rapid microwave technique by employing citric acid with L-glutamine followed by boron functionalization using boric acid for the synthesis of boron-nitrogen doped carbon dots (BN-CDs) by using reflux reaction condition. These BN-CDs exhibited outstanding photo-stability, excellent aqueous dispersibility, low cytotoxicity, and high photoluminescence quantum yield (QY) of ∼ 21.9 ± 2.7 % and emitted green fluorescence under UV light. BN-CDs were found to display photoluminescence quenching very specific towards auric ions (Au3+ ions) with a detection limit of 3.1 ± 0.45 nM. The quenching observed in the detection process was primarily due to coordination-induced aggregation mechanism. Moreover, BN-CDs were also found to have superior radical scavenging activity, excellent cytocompatibility and cell imaging properties. Thus, prepared BN-CDs can have potential applications in the accurate detection of auric ions as well as in cell imaging applications.

In this investigation, we have developed a highly efficient and robust electrode nanocomposite tailored for the electrochemical sensing of 4-nitroaniline (4-NA), a hazardous pollutant. We synthesized a three-dimensional flower-like molybdenum disulfide (MoS2) embedded tungsten carbide (WC) nanocomposite utilizing a straightforward ultrasonic technique. This nanocomposite was integrated onto a screen-printed carbon electrode (SPCE) and optimized for electrochemical detection. Under these optimal conditions, the MoS2/WC nanocomposite demonstrates remarkable analytical performance for 4-NA detection, characterized by two distinguishable linear concentration ranges of 2-458 μM and 458-1288 μM. The sensor exhibits a sensitivity of 1.38 μA μM-1 cm-2 and a low detection limit of 0.034 μM, highlighting its potential for effective real-time monitoring of 4-NA in environmental samples. The enhanced performance of the MoS2/WC/SPCE can be attributed to the synergistic effect of individual MoS2 (large specific surface area, unique structural characteristics) and WC (high conductivity, increased number of active surface sites, and high stability). The MoS2/WC nanocomposite demonstrates superior electrocatalytic performance for the reduction of 4-NA in neutral electrolytes compared to previously reported electrocatalysts. Moreover, the MoS2/WC-modified SPCE shows remarkable selectivity and good reproducibility in detecting 4-NA. This innovative approach holds significant promise for advancing environmental application outcomes for real-time sensing applications.

Water splitting is a promising method for hydrogen production, providing a clean energy source with a high energy yield. To meet long-term global energy demands, breakthroughs in hydrogen production, storage, and transportation are crucial. The direct use of seawater for hydrogen production is gaining popularity, as it reduces costs and efficiently utilizes saltwater resources. Technologies like photocatalysis, electrocatalysis, and photoelectrocatalysis facilitate seawater splitting by converting sunlight into hydrogen fuel, thus enabling green hydrogen production. For example, photocatalytic hydrogen generation mimics artificial photosynthesis, offering a simple and cost-effective approach. Our review of research on photo/electrocatalytic seawater splitting highlights both its limitations and future potential for sustainable fuel sources. Key challenges, such as low conversion efficiency and catalyst instability, need to be addressed. Future studies should focus on developing stable catalysts and optimizing mass transport at the electrode-electrolyte interface.

The phenothiazine-based fluorometric chemosensor, N′,N‴-((1E,1′E)-(10-ethyl-10H-phenothiazine-3,7-diyl)bis(methaneylylidene))bis(4-methylbenzenesulfonohydrazide) (L), has been meticulously designed, synthesized, and evaluated for its capabilities in metal ion detection. This sensor exhibits a remarkable selectivity for Cu2+ and Fe3+ ions, showcasing its potential applicability over a spectrum of other common metal cations in acetonitrile (CH3CN) solution. The interaction with Cu2+ and Fe3+ results in a distinctive fluorescence on–off response. Impressively low detection limits of 5.54 × 10−9 M for Cu2+ and 3.11 × 10−9 M for Fe3+ have been achieved, attesting to the high sensitivity of the sensor. The recognition mechanism of L towards Cu2+ and Fe3+ has been systematically investigated through various analytical approaches. Job plot measurements, Fourier-transform infrared (FT-IR) titration, and high-resolution mass spectrometry (HRMS) have provided insightful details regarding the binding stoichiometry and nature of the interactions between L and the target metal ions. Beyond fundamental characterization, the practical utility of the probe has been demonstrated in the bio-imaging of Cu2+ and Fe3+ in a mouse fibroblast cell line (NIH3T3), underscoring its potential for biological applications. Additionally, the sensor has been successfully employed for the quantification of Cu2+ and Fe3+ in real samples, showcasing its versatility in environmental monitoring. The results collectively highlight the efficacy of L as a robust chemosensor with significant potential for various analytical and biomedical applications, contributing to the growing repertoire of metal ion detection methodologies.

Three-dimensional (3D)-bioprinting is widely used in tissue engineering due to its customizability, avoidance of allogeneic rejection, and absence of disease transmission risk. Cellulose, a renewable natural polymer, is valued as an excellent bioink for its non-toxicity, biocompatibility, biodegradability, and cost-effectiveness. In this study, 2,2,6,6-tetramethylpiperidine-1-oxyl radical-oxidized microcellulose was subjected to homogenization. The resulting bioink was characterized using Fourier transform infrared spectroscopy, conductivity measurements, and rheometric analyses. Scaffolds were subsequently fabricated using 3D bioprinting, and cell viability was evaluated through cell culture on the printed scaffold. Optimization of the oxidation process revealed that a 6-h treatment achieved the highest degree of oxidation, exhibiting superior viscosity and printability compared to other durations. A straightforward scale-up of the 6-h process enabled the successful fabrication of 3D-bioprinted scaffolds. Cell culture experiments demonstrated excellent cell adhesion and viability on the scaffolds. Our findings demonstrate that oxidized microcellulose serves as a promising bio-based, non-toxic, structurally stable, and cell-compatible bioink for 3D bioprinting in tissue engineering applications.

Diabetes is emerging as a significant health and societal concern globally, impacting both young and old populations. In individuals with diabetic foot ulcers (DFUs), the wound healing process is hindered due to abnormal glucose metabolism and chronic inflammation. Minor injuries, blisters, or pressure sores can develop into chronic ulcers, which, if left untreated, may lead to serious infections, tissue necrosis, and eventual amputation. Current management techniques include debridement, wound dressing, oxygen therapy, antibiotic therapy, topical application of antibiotics, and surgical skin grafting, which are used to manage diabetic wounds and foot ulcers. This review focuses on a hydrogel-based strategy for phase-wise targeting of DFUs, addressing sequential stages of diabetic wound healing: hemostasis, infection, inflammation, and proliferative/remodeling phases. Hydrogels have emerged as a promising wound care solution due to their unique properties in providing a suitable wound-healing microenvironment. We explore natural polymers, including hyaluronic acid, chitosan, cellulose derivatives, and synthetic polymers such as poly (ethylene glycol), poly (acrylic acid), poly (2-hydroxyethyl methacrylate, and poly (acrylamide), emphasizing their role in hydrogel fabrication to manage DFU through phase-dependent strategies. Recent innovations, including self-healing hydrogels, stimuli-responsive hydrogels, nanocomposite hydrogels, bioactive hydrogels, and 3D-printed hydrogels, demonstrate enhanced therapeutic potential, improving patient outcomes. This review further discusses the applicability of various hydrogels to each phase of wound healing in DFU treatment, highlighting their potential to advance diabetic wound care through targeted, phase-specific interventions.

Nanoceria, a potent nanozyme, widely explored for biomedical applications, often faces toxicity and stability issues when synthesized chemically. In this study, nanoceria (NC-G) is synthesized via a simple green method using Terminalia arjuna extract as a reducing and capping agent and is compared with chemically synthesized nanoceria (NC-C) for stability, antioxidant, and anti-cancer properties. The mean sizes and surface charge of NC-C and NC-G was found to be 37.78 ± 15.5 nm (-16.2 ± 7.6 mV) and 21.8 ± 5.3 nm (-51.4 ± 8.9 mV) respectively. The percentage of Ce 3 + and Ce 4+ was determined using XPS analyses. Superoxide dismutase (SOD), catalase and antioxidant regenerative properties of NC-G was determined to have better performance than NC-C. Thus, NC-G demonstrated an improvement in cyto-compatibility when compared to NC-C using MTT assay. Moreover, NC-G showed enhanced intracellular antioxidant and cyto-protective properties under oxidative stress in rat cardiomyocytes cell line (H9C2). Further, both NC-C and NC-G showed dose-dependent anti-cancerous activity towards human breast cancer cell line (MCF7), with NC-G demonstrating enhanced pro-oxidant properties on MCF7 cells. The results from this study indicate that NC-G could be a potential nanomedicine as an antioxidant therapy in cardiovascular diseases or as pro-oxidant therapeutics in oncology.

In recent years, significant toxicity of silver ions (Ag+) to the environment and human body has garnered attention to their detection in biological samples and aqueous solutions. In this work, we synthesized boron/nitrogen-doped carbon dots (LBN-CDs) as a fluorescent sensor with excellent selectivity for silver ions (Ag+) detection. First, a one-pot microwave-assisted approach was employed to directly develop nitrogen-doped carbon dots (N-CDs) from L-ascorbic acid and L-glutamine. Subsequently, boron co-doping on the N-CDs were achieved by reaction with boric acid, and the quantum yield was determined to be ∼34 ± 1.8 %. Bright green fluorescence and strong water solubility, including favorable photostability properties, salt tolerance, and pH stability, were demonstrated by the resulting LBN-CDs. It was found that adding Ag+ ions through electron transfer to create a nonfluorescent complex had quenched the fluorescence intensity of the LBN-CDs. With a detection limit (LOD) of ̴ 3.7 ± 0.18 nM, the silver ions in this case quenched the photoluminescence (PL) of the LBN-CDs more strongly than other heavy metals, which indicated that the synthesized LBN-CDs can be effectively used as Ag+ ions sensing probe with high sensitivity and selectivity. The examination of Ag+ ions in real water samples further confirmed the efficiency of this fluorescent probe in sensing silver ions. Further, using mouse fibroblast cell line, NIH-3T3, LBN-CDs were found to be cyto-compatible and have good bioimaging properties. LBN-CDs will therefore be a promising cell imaging agent and platform for selectively detecting Ag+ ions in water via nano-sensing.

High-entropy alloys (HEAs) have gained considerable attention for their exceptional properties, positioning them as promising candidates for the advancement of energy conversion and storage systems. This review offers a comprehensive overview of recent developments in catalysis related to HEAs, focusing on critical areas such as the hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, hydrogen storage, zinc–air batteries, and supercapacitors. We begin by exploring the foundational aspects of HEAs, including component selection, strategies for achieving a stable single solid solution phase, and effective synthesis methods. The review emphasizes that HEAs exhibit superior electrocatalytic activity, cycling stability, and durability compared to traditional noble metal catalysts, making them highly effective as anode and cathode materials in electrochemical energy storage systems. In hydrogen storage applications, HEAs demonstrate significant capacity and stability as metal hydrides, facilitating efficient hydrogen absorption and desorption. Additionally, in zinc–air batteries, HEAs enhance performance through improved electrocatalytic activity for oxygen reduction and evolution reactions. In supercapacitors, their large surface area and excellent electrical conductivity contribute to enhanced energy storage efficiency. Finally, we outline potential future directions and emerging technologies that could leverage the unique properties of HEAs, underscoring their role in shaping the future of energy-related applications.

The development of efficient and accurate methods for detecting antipsychotic drugs is essential for preventing drug abuse. In this study, we designed a 2D/2D molybdenum diselenide/vanadium carbide (MoSe2/VC) nanocomposite for the electrochemical detection of chlorpromazine (CLPZ). Additionally, the cytotoxic properties of the MoSe2/VC nanocomposite were evaluated to assess its impact on cell health. The morphological structure and physical properties were thoroughly characterized using spectroscopic and microscopic techniques. Under optimized experimental conditions, the MoSe2/VC modified electrode exhibited excellent linearity (0.01–462 μM), a limit of detection of (0.013 ± 0.03 μM), high sensitivity (2.095 ± 0.04 μA μM–1 cm–2), robust selectivity (<5 %), and reproducibility of 2.21 % for CLPZ. The enhanced performance of the MoSe2/VC nanocomposite can be attributed to synergistic effects, increased surface area, unique structural characteristics, high conductivity, exceptional electrocatalytic activity, and a greater number of active surface sites, all of which contribute to improved CLPZ detection performance. Notably, the proposed sensor was employed for the quantitative analysis of CLPZ in spiked real samples, achieving satisfactory recoveries of 97.1–99.2 %. Furthermore, cell viability studies conducted with L-929 fibroblast cells demonstrated high biocompatibility, with cell survival rates exceeding 82 %. These findings highlight the promise of the MoSe2/VC nanocomposite-based electrochemical sensor as an affordable, effective, and dependable tool for environmental monitoring and safeguarding public health.

Semiconductor-based quantum dots (QDs) are zero-dimensional fluorescent nanomaterials composed of groups II–VI, III–V or IV elements, having excellent optical and electronic properties. QDs are considered advantageous over conventional fluorescent organic dyes due to their tunable broad excitation and narrow emission spectra, high quantum yield, enhanced signal-to-noise ratio, and photostability. With the advent of water-soluble QDs in the late 1990s, there was an explosion of QDs-based research in biomedical arena especially in the bioimaging and diagnosis applications. This chapter deals with various types of QDs, their unique optical properties due to quantum mechanical effects, various synthesis, and characterization techniques and elaborates in detail about their biomedical applications especially focusing on the disease diagnoses aspects like immunolabeling, nucleic acid detection, tumor detection; live cells imaging techniques, and finally the recent advancement in the detection of harmful pathogens and toxins.

Polymeric biomaterials are found to have extensive applications in nanomedicine mainly for delivery of drugs and tissue engineering-regenerative applications. Poly(lactide-co-glycolic acid) (PLGA), in particular, has been efficiently utilized for its synthetic plasticity, biocompatibility, and most importantly its FDA approval status. In the past two decades, PLGA has been among the widely used polymeric materials to fabricate devices for the controlled/sustained/targeted delivery of small molecules, proteins, DNA/RNA/peptide molecules as well as other tissue engineering applications. Hybrid-type nanocomposites have also emerged as an enthusiasm for drug delivery system development with flexible physical and chemical properties that have explicit therapeutic potential and minimal side effects. There are some commercially available PLGA products, but the available systems still have many defects due to their development and manufacturing, such as wide size distribution and issues with drug stability. New advances and optimizations in the previous studies could bring a new path of “smart tools” in the development of personalized, noninvasive emerging nanomedicine.

Poly(amidoamine), a polymer with several amide and amine groups are widely explored in biomedical field as dendrimers, which are monodispersed, synthetic, three-dimensional, hyperbranched nano-polymeric structured substances that are commonly regarded as homogeneous molecules. PAMAM dendrimers, also commercially known as “Starburst” are employed widely in gene/drug delivery as well as materials of choice for several supramolecular chemistry applications. Many important biological features, including bioavailability, solubility, and selectivity, can be improved by entrapping bioactive molecules into the dendrimer frame. One of the more sophisticated uses of PAMAM is in their instructing groups to achieve selective delivery in desired organs of choice. This chapter discusses several PAMAM synthesis techniques, its surface modifications, and biomedical applications. The features of supramolecular PAMAM dendrimers in nano polymer research have been demonstrated substantially in gene transport, drug delivery, and many other applications when compared to other normal nano polymers.

Phytochemicals are found to have enormous therapeutic potential and have been under investigation for the treatment of a variety of diseases for several years now. However, they suffer from various inherent limitations, such as poor solubility, low stability, poor bioavailability, and low gastric stability upon oral dosage. To overcome the aforementioned limitations, the phytochemicals are essentially encapsulated inside materials of choice, typically in nano, micro, or other formulations to improve their efficacy and bioavailability. This chapter begins by elaborating on the various material fabrication strategies reported for the synthesis of phytochemicals-incorporated nanoparticles, microparticles, liposomes, nanofibers, hydrogels, polymeric patches, and scaffolds, and their biomedical applications are also discussed. Moreover, this chapter also covers the recent advancements in the field of phytochemicals-based formulations such as 3D printed formulations, microneedles-based implants, and finally plant-derived exosomes, which are natural lipid-based nanovesicles that have excellent biomedical applications.

Plant-based hydrogels have wide application as scaffolds in tissue engineering and regenerative medicine due to their low cost and excellent biocompatibility. Scaffolds act as vehicles for cell-based therapeutics and regenerating diseased tissue. While there is a plethora of methods to generate hydrogels with tunable properties to mimic the tissue of interest, 3D bioprinting is a novel emerging technology with the capability to generate versatile patient-specific scaffolds typically embedded with tissue specific cells. Starch-based hydrogels are garnering attention in extrusion-based 3D printing, however owing to their poor mechanical strength and degradation render this material inefficient in its native form. Additionally, the effect of various printing process parameters on mechanical strength and bioactivity is poorly understood. In the present study, we investigate the use of starch and gelatin as composite biomaterial ink and its effect on mechanical, physical and biological properties. We also investigated printability of composite hydrogels with the aim to understand the correlation between two infill patterns and its effect on mechanical, physicochemical, and biological properties. Our results showed that the composite hydrogels had competent mechanical properties and suitable bioactivity when seeded with H9C2 cardiomyocytes. Rheometric analyses provided a broader insight into the required viscosity for printing and has a direct correlation with the composition of the hydrogel. Thus, the composite materials are found to have tissue-specific mechanical properties and may serve as a better, cheaper and personalized alternative to existing scaffolds for the fabrication of engineered cardiac tissue.

Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity, often associated with pancreatic β cells impairment, leads to hyperglycemia, a hallmark of diabetes. Type 1 diabetes (T1D) results from autoimmune destruction of β cells, while type 2 diabetes (T2D) stems from genetic, environmental, and lifestyle factors causing β cell dysfunction and insulin resistance. Currently, insulin therapy is used for most of the cases of T1D, while it is used only in a few persistent cases of T2D, often supplemented with dietary and lifestyle changes. The key challenge in oral insulin delivery lies in overcoming gastrointestinal (GI) barriers, including enzymatic degradation, low permeability, food interactions, low bioavailability, and long-term safety concerns. The muco-adhesive (MA) and muco-penetrative (MP) formulations aim to enhance oral insulin delivery by addressing these challenges. The mucus layer, a hydrogel matrix covering epithelial cells in the GI tract, poses significant barriers to oral insulin absorption. Its structure, composition, and turnover rate influence interactions with insulin and other drug carriers. Some of the few factors that influence mucoadhesion and mucopenetration are particle size, surface charge distribution, and surface modifications. This review discusses the challenges associated with oral insulin delivery, explores the properties of mucus, and evaluates the strategies for achieving excellent MA and MP formulations, focusing on nanotechnology-based approaches. The development of effective oral insulin formulations holds the potential to revolutionize diabetes management, providing patients with a more convenient and patient-friendly alternative to traditional insulin administration methods.

The emerging drug diclofenac (DICF) has been found to penetrates aquatic systems at alarming concentrations and poses serious and irreversible ecotoxicological threats around the world. In this work, we present the solid-state mechanochemical synthesis of 3D flower-like bismuth oxyhalides (BiOX, where X = Cl, Br, and I) as electrode materials for electrochemical detection of DICF. The characteristics of the flower-like BiOX are systematically investigated using spectroscopic and microscopic techniques. The BiOI-modified glassy carbon electrode (GCE) exhibits superior electrochemical performance for DICF detection compared to the pristine GCE, BiOCl/GCE, and BiOBr/GCE. The 3D flower-like architecture of BiOI facilitates favorable electrocatalytic activities due to its abundant electroactive sites, good conductivity, large surface area, and fast ion diffusion. Notably, the BiOI/GCE displays wide linear ranges (0.5–11.3 & 11.3−76), a low limit of detection (0.11 μM), high sensitivity (1.33 μA μM–1 cm–2), excellent repeatability (2.91 %), good reproducibility (2.88 %), and anti-interfering ability (<±5 %). To validate the practicality of the fabricated BiOI/GCE, the quantitative detection of DICF in human urine and river water is demonstrated and achieves acceptable recovery values. This study introduces an innovative approach to design and produce electrode materials with distinct properties, enabling enhanced electrocatalysis for various electrochemical sensing applications.

A Schiff-base Ethyl (E)-2-(3-((2-carbamothioylhydrazono)methyl)-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (TZTS) dual functional colorimetric and photoluminescent chemosensor which includes thiazole and thiosemicarbazide has been synthesized to detect arsenic (As3+) ions selectively in DMSO: H2O (7:3, v/v) solvent system. The molecular structure of the probe was characterized via FT-IR, 1H, and 13C NMR & HRMS analysis. Interestingly, the probe exhibits a remarkable and specific colorimetric and photoluminescence response to As3+ ions when exposed to various metal cations. The absorption spectral changes of TZTS were observed upon the addition of As3+ ions, with a naked eye detectable color change from colorless to yellow color. Additionally, the chemosensor (TZTS) exhibited a new absorption band at 412 nm and emission enhancements in photoluminescence at 528 nm after adding As3+ ions. The limit of detection (LOD) for As3+ ions was calculated to be 16.5 and 7.19 × 10−9 M by the UV–visible and photoluminescent titration methods, respectively. The underlying mechanism and experimental observations have been comprehensively elucidated through techniques such as Job's plot, Benesi-Hildebrand studies, and density functional theory (DFT) calculations. For practical application, the efficient determination of As3+ ions were accomplished using a spike and recovery approach applied to real water samples. In addition, the developed probe was successfully employed in test strip applications, allowing for the naked-eye detection of arsenic ions. Moreover, fluorescence imaging experiments of As3+ ions in the breast cancer cell line (MCF-7) demonstrated their practical applications in biological systems. Consequently, these findings highlight the significant potential of the TZTS sensor for detecting As3+ ions in environmental analysis systems.

In this work, we developed a fast and straightforward colorimetric and photoluminescent chemosensor probe (P1), featuring bis-thiophene-thiosemicarbazide moieties as its signaling and binding unit. This probe exhibited rapid sensitivity to Hg2+ and Cu2+ ions in a semi-aqueous medium, resulting in distinct colorimetric and photoluminescent changes. In the presence of Cu2+, P1 displayed an impressive 50-fold increase in photoluminescence (PL) at 450 nm (with excitation at 365 nm). The probe P1 formed a 1:1 complex with Hg2+ and Cu2+ ions, featuring association constant values of 4.04 × 104 M−1 and 1.25 × 103 M−1, respectively. P1 has demonstrated its efficacy in the analysis of real samples, yielding promising results. Additionally, the probe successfully visualized copper ions on a mouse fibroblast cell line (NIH3T3), highlighting its potential as an intracellular probe for copper ion detection.

Environmental monitoring of organic pollutants in water sources is crucial for protecting human health and ecosystem sustainability. Herein, we develop a highly active electrocatalyst composite consisting of cauliflower-like calcium molybdate (CaMoO4) decorated with sulfur-doped graphitic carbon nitride (S–C3N4) for the ultrasensitive electrochemical detection of organic pollutant metol. Various microscopic and spectroscopic techniques were employed to analyze the structural and compositional characteristics of the S–C3N4/CaMoO4 composite. The electrochemical sensor with the optimized S–C3N4/CaMoO4 composite demonstrates a high sensitivity of 3.93 μA μM−1 cm−2 and a low limit of detection of 0.002 μM in a wide linear range (0.01–134 μM) by the DPV method. The excellent performance can be attributed to their high conductivity, high surface area, swift electron transportation, favorable active sites, and synergistic effect. Besides, the proposed electrochemical sensor exhibits good reproducibility and remarkable selectivity in the presence of various potential interference compounds in water sources. Its practical applicability for environmental monitoring is verified by quantifying metol in tap water, lake water, and river water. This work highlights the feasibility of rapid and robust electrochemical sensing of the organic pollutant metol at low concentrations and validates its suitability for the in-field applications.

Graphitic carbon nitride (g–C3N4), an organic photocatalyst was reported to have beneficial properties to be used in wastewater treatment applications. However, g–C3N4, in its bulk form was found to have poor photocatalytic degradation efficiency due to its inherent limitations such as poor specific surface area and fast electron–hole pair recombination rate. In this study, we have tuned the physiochemical properties of bulk g–C3N4 by direct thermal exfoliation (TE–g–C3N4) and examined their photocatalytic degradation efficiency against abundant textile dyes such as methylene blue (MB), methyl orange (MO), and rhodamine B (RhB). The degradation efficiencies for MB, MO, and RhB dyes are 92 ± 0.18%, 93 ± 0.31%, and 95 ± 0.4% respectively in 60 min of UV light irradiation. The degradation efficiency increased with an increase in the exfoliation temperature. The prepared catalysts were characterized using FTIR, XRD, FE-SEM, EDAX, BET, and UV-DRS. In BET analysis, TE–g–C3N4 samples showed improved surface area (48.20 m2/g) when compared to the bulk g–C3N4 (5.03 m2/g). Further, the TE–g–C3N4 had 2.98 times higher adsorption efficiency than the bulk ones. The free radicals scavenging studies revealed that the superoxide radicals played an important role in the photodegradation for dyes, when compared to the hydroxyl radical (.OH) and the photo-induced holes (h+), Photoluminescence (PL) emission and electrochemical impedance spectroscopy (EIS) spectra of TE–g–C3N4 indicated a lowered electron–hole pairs’ recombination rate and an increased photo-induced charge transfer respectively. Further, the TE–g–C3N4 were found to have excellent stability for up to 5 cycles with only a minor decrease in the activity from 92% to 86.2%. These findings proved that TE–g–C3N4 was an excellent photocatalyst for the removal and degradation of textile dyes from wastewater.

The process involved in the discovery of novel drugs in medical sciences is challenging due to the time-intensive process that results in a high cost of development. Additionally, it is reported that 90 % of new drugs fail in clinical trials and cannot reach the market. One of the primary reasons for failure is that research laboratories and pharmaceutical companies have been relying exclusively on data derived from animal-based models for testing the efficacy and safety of newly developed drugs. These models do not completely recapitulate human physiology or pathophysiology, resulting in a lower translational rate. Further, the evaluation of toxicity of drugs to the human body requires a more robust and holistic approach. Researchers across the globe are focusing on developing in vitro3D models as alternatives to traditional animal testing to circumvent these challenges. These model systems could replicate and mimic the human physiological microenvironment, cellular interactions, and arrangements. In vitro3D models would provide improved methods to evaluate and comprehend drug response, thereby reducing the burden on animal usage. Further, reducing the time and costs associated with developing, screening, drug failure, and translation of drugs is also realizable. In this communication, existing in vitro 3D models that are used in the drug development process are reviewed. In addition, the advancements in using 3D bioprinting and organ-on-a-chip technologies towards generating human reconstructed tissues/organs are also highlighted. The challenges from a technological and regulatory perspective on adapting these alternate animal models are also discussed.

3D bioprinting is an emerging technology for the fabrication of tissue constructs to repair damaged or diseased human tissues or as in vitro model systems for drug screening applications. Biomaterial-inks (polymeric hydrogel materials devoid of cells) or bio-inks (combination of polymeric hydrogel materials and cells) form the basis of 3D bioprinting. Successful 3D bioprinting requires optimisation of various process parameters such as biomaterial/bio inks’ viscoelastic, mechanical, and physiochemical properties which influence the printability. However, clinical translation of 3D bioprinted constructs requires that implantable devices are free of microbial contamination and further do not invoke microbial activity post implantation. Sterilization plays an important role in ensuring that inks are free of microorganisms. Recent investigations have shown that sterilization techniques directly influence the intrinsic properties of these inks, thereby affecting bioprinting process parameters. In this communication, we review the most common sterilization techniques that are used in the sterilization of biomaterial/bio inks and their effects on the inks’ properties such as viscoelasticity, mechanical, physiochemical and biological properties, and their influence on bioprinting parameters. To conclude, the available studies in the literature indicate that the sterilization processes influence the properties of biomaterial inks. Thus, the effect of sterilization methods on the materials’ properties needs to be thoroughly evaluated and reported while developing them for 3D bioprinting applications.

Background: Hyaluronic acid (HA) is a naturally occurring biodegradable, high molecular weight, non-sulfated glycosaminoglycan (GAG) polymer known for its excellent biocompatibility. HA-based products are widely used as viscosupplements, dermal fillers, and ophthalmic lubricants in clinical settings. Although animal and bacterial-derived HA are commonly reported, plant-sourced HA is not frequently reported. In this study, we have evaluated various viscoelastic properties of one such plant-based HA solution and propose them as an alternative to existing animal/bacteria-sourced HA. Materials and Methods: The viscoelastic properties of plant-sourced HA solution of various concentrations (0.1%, 0.5%, 1%, and 2% in PBS) were studied using a rheometer at 37°C. Flow curves, amplitude sweep studies, and frequency sweep studies were performed and compared for all HA solutions. Results: The HA solutions displayed shear-Thinning behavior, which is an important characteristic of an injectable biomaterial. The 0.1 and 0.5% HA were found to have viscoelastic properties appropriate for eye lubricants, while 1 and 2% HA solutions showed properties suitable for soft tissue fillers. Frequency sweep studies indicated that all the samples are typically viscoelastic liquids with a loss modulus (G″) higher than the storage modulus (G′). This indicated that the samples needed further processing like crosslinking of HA or using higher molecular weight HA to be suitable as viscosupplements. However, the frequency sweep studies also indicated that these solutions can be used as soft tissue fillers of any type based on the G′ and tan δ values. Conclusion: The plant-sourced HA solutions are found to exhibit good shear-Thinning properties with viscoelastic properties suitable for eye lubricants and soft tissue fillers. However, to be used as viscosupplements, the viscoelastic properties of HA solutions have to be further modified through non-Toxic crosslinking strategies, and hydrophobic derivatives as well as by using high molecular weight HAs.

The paper develops an investigative ZigBee IoT based intelligent lane control mechanism for India's first field ready electric tractors, Sonalika Tiger Electric to operate with the chosen constraints. It employs the state-of-the-art Microcontroller based embedded system to govern the comprehensive requirements in accordance with the changes that the vehicle either experiences or becomes necessary for it to negotiate. The design involves the bounding of the parameters that include the vehicle speed, engine speed, battery SoC (State of Charge), battery SoH (State of Health), a real time GPS navigator along with Edge/ Boundary Detection Algorithm which enters the system using ZigBee enabled wireless sensors and IoT based maps to incorporate the lane control system. It primarily ensures a close monitoring methodology to develop a sequence of steps that allow the system to remain in operation over scheduled durations. The procedure involves a simulation process carried out using embedded-c firmware code to epitomize the virtues of the proposed scheme and elicit the performance of the chosen vehicle in terms of its ability to operate at the predefined constraints.

Background: The stromal vascular fraction (SVF) is an aqueous fraction isolated from the adipose tissue that constitutes different kinds of cells and extracellular matrix components. Hyaluronic acid (HA) is a linear polysaccharide in vertebrate tissues and is considered a potential tissue engineering scaffold due to its biocompatible nature. In this study, we have evaluated the cytotoxicity of xenofree HA in combination with an acellular component of adipose SVF (HA-ASVF) to propose it as a candidate biomaterial for future applications. Materials and Methods: 3-(4,5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide assay of L-929 cells treated with HA-ASVF was used in our study. Data were normalized to cell control (untreated) and extracts of copper and ultra-high molecular weight polyethylene were used as positive (PC) and negative controls (NC). Results: Fibroblast cells retained the morphology after 24 h of treatment with HA-ASVF mixture and exhibited a similar percentage of cell activity compared to NC. PC showed a positive cytotoxic response as expected. The cells incubated with HA-ASVF showed a linear increase in cell activity indicating proliferation. Conclusion: The mixture of HA and acellular SVF in its flowable form is non-cytotoxic and showed improved cell proliferation. Hence the mixture can be proposed as a biomaterial and can be further explored for specific tissue engineering applications.

Sweat, a biofluid secreted naturally from the eccrine glands of the human body, is rich in several electrolytes, metabolites, biomolecules, and even xenobiotics that enter the body through other means. Recent studies indicate a high correlation between the analytes’ concentrations in the sweat and the blood, opening up sweat as a medium for disease diagnosis and other general health monitoring applications. However, low concentration of analytes in sweat is a significant limitation, requiring high-performing sensors for this application. Electrochemical sensors, due to their high sensitivity, low cost, and miniaturization, play a crucial role in realizing the potential of sweat as a key sensing medium. MXenes, recently developed anisotropic two-dimensional atomic-layered nanomaterials composed of early transition metal carbides or nitrides, are currently being explored as a material of choice for electrochemical sensors. Their large surface area, tunable electrical properties, excellent mechanical strength, good dispersibility, and biocompatibility make them attractive for bio-electrochemical sensing platforms. This review presents the recent progress made in MXene-based bio-electrochemical sensors such as wearable, implantable, and microfluidic sensors and their applications in disease diagnosis and developing point-of-care sensing platforms. Finally, the paper discusses the challenges and limitations of MXenes as a material of choice in bio-electrochemical sensors and future perspectives on this exciting material for sweat-sensing applications.

Molecularly imprinted polymers (MIPs), a biomimetic artificial receptor system inspired by the human body’s antibody-antigen reactions, have gained significant attraction in the area of sensor development applications, especially in the areas of medical, pharmaceutical, food quality control, and the environment. MIPs are found to enhance the sensitivity and specificity of typical optical and electrochemical sensors severalfold with their precise binding to the analytes of choice. In this review, different polymerization chemistries, strategies used in the synthesis of MIPs, and various factors influencing the imprinting parameters to achieve high-performing MIPs are explained in depth. This review also highlights the recent developments in the field, such as MIP-based nanocomposites through nanoscale imprinting, MIP-based thin layers through surface imprinting, and other latest advancements in the sensor field. Furthermore, the role of MIPs in enhancing the sensitivity and specificity of sensors, especially optical and electrochemical sensors, is elaborated. In the later part of the review, applications of MIP-based optical and electrochemical sensors for the detection of biomarkers, enzymes, bacteria, viruses, and various emerging micropollutants like pharmaceutical drugs, pesticides, and heavy metal ions are discussed in detail. Finally, MIP’s role in bioimaging applications is elucidated with a critical assessment of the future research directions for MIP-based biomimetic systems.

The culturing of cells in the laboratory under controlled conditions has always been crucial for the advancement of scientific research. Cell-based assays have played an important role in providing simple, fast, accurate, and cost-effective methods in drug discovery, disease modeling, and tissue engineering while mitigating reliance on cost-intensive and ethically challenging animal studies. The techniques involved in culturing cells are critical as results are based on cellular response to drugs, cellular cues, external stimuli, and human physiology. In order to establish in vitro cultures, cells are either isolated from normal or diseased tissue and allowed to grow in two or three dimensions. Two-dimensional (2D) cell culture methods involve the proliferation of cells on flat rigid surfaces resulting in a monolayer culture, while in three-dimensional (3D) cell cultures, the additional dimension provides a more accurate representation of the tissue milieu. In this review, we discuss the various methods involved in the development of 3D cell culture systems emphasizing the differences between 2D and 3D systems and methods involved in the recapitulation of the organ-specific 3D microenvironment. In addition, we discuss the latest developments in 3D tissue model fabrication techniques, microfluidics-based organ-on-a-chip, and imaging as a characterization technique for 3D tissue models.

Herbal medicines were the main source of therapeutic agents in the ancestral era. Terminalia arjuna (TA) is one such medicinal plant widely known for its several medicinal properties, especially its cardiovascular properties. They have several phytochemicals, such as flavonoids, polyphenols, triterpenoids, tannins, glycosides, and several minerals, proteins, and others that are responsible for the above-mentioned medicinal properties. In this review, we have first elaborated on the various processes and their parameters for the efficient extraction of relevant phytochemicals from TA extracts. Secondly, the mechanisms behind the various medicinal properties of TA extracts are explained. We have also highlighted the role of TA extracts on the green synthesis of metallic nanoparticles, especially silver and gold nanoparticles, with an elucidation on the mechanisms behind the synthesis of nanoparticles. Finally, TA extracts-based polymeric formulations are discussed with limitations and future perspectives. We believe that this review could help researchers understand the importance of a well-known cardioprotective medicinal plant, TA, and its biomedical properties, as well as their role in green nanotechnology and various formulations explored for encapsulating them. This review will help researchers design better and greener nanomedicines as well as better formulations to improve the stability and bioavailability of TA extracts.

Titanium dioxide (TiO2)-based nanostructures have wide applications in cosmetics, toothpastes, pharmaceuticals, coatings, papers, inks, plastics, food products, textiles, and many others. Recently, they have also been found to have huge potential as stem cells’ differentiation agents as well as stimuli-responsive drug delivery systems in cancer therapy. In this review, we present some of the recent progress in the role of TiO2-based nanostructures toward the above-mentioned applications. We also present recent studies on the toxicity issues of these nanomaterials and the mechanisms behind the toxicity issues. We have reviewed the recent progress of TiO2-based nanostructures on their stem cells’ differentiation potentials, their photo- and sono-dynamic capabilities, as stimuli-responsive drug delivery systems, and finally their toxicity issues with mechanistic understanding on the same. We believe that this review will help researchers be aware of the latest progress in the applications as well as few toxicity issues associated with TiO2-based nanostructures, which will help them design better nanomedicine for future applications.

Recent advancements in the use of phytoconstituents in either conjugated or encapsulated form with different nanocarriers is a new area of interest in the field of disease therapy. Plant active ingredients, or phytochemicals, are predominantly secondary metabolites that are reported to be beneficial in several clinical applications, like bacterial infection, wound healing, and cancer. However, their biological activity is limited by poor solubility, short half-lives, and quick clearance from the body. Nanotechnology has emerged as an efficient platform for overcoming these drawbacks to effectively deliver phytochemicals. This book chapter focuses on recent breakthroughs in nanocarriers, especially carbon-based nanoparticles and metallic nanoparticles, as potential solutions for improved delivery of these plant-derived phytochemicals. Moreover, several advantages offered by these phytomedicine nanoformulations have been highlighted. Overall, we have emphasized the evolving applications and pioneering progress of metallic and carbon-based nanocarriers for the delivery of plant active ingredients.

Axial suspension plasma spraying (ASPS) is an alternative technique to atmospheric plasma spraying (APS), which uses a suspension of much finer powders (<5-micron particle size) as the feedstock. It can produce more refined microstructures than APS for biomedical implants. This paper highlights the influence of incorporated graphene nanoplatelets (GNPs) on the behavior of ASPS hydroxyapatite (HAp) coatings. The characterization of the ASPS coatings (HAp + varying GNP contents) was carried out using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), confocal Raman microscopy (CRM), white light interferometry (WLI), and contact angle measurements. The evaluation of the mechanical properties such as the hardness, roughness, adhesion strength, and porosity was carried out, along with a fretting wear performance. Additionally, the biocompatibility of the Hap + GNP coatings was evaluated using cytotoxicity testing which revealed a decrease in the cell viability from 92.7% to 85.4%, with an increase in the GNP wt.%. The visualization of the cell’s components was carried out using SEM and Laser Scanning Microscopy. Furthermore, the changes in the genetic expression of the various cellular markers were assessed to analyze the epigenetic changes in human mesenchymal stem cells. The gene expression changes suggested that GNPs upregulated the proliferation marker and downregulated the pluripotent markers by a minimum of three folds.

This chapter deals with the emerging applications of 3D printing (3DP) technologies to tackle the recent pandemic, the Corona viral disease (COVID-19). The chapter throws light on the role of 3DP technologies and other allied hybrid technologies for the development of novel products to satiate the shortage of personal protective equipment (PPE) such as face shields, masks, eye protection devices, ventilator tubes, and other medical devices needed to tackle COVID-19. It also explicates the hybrid additive processes required to fabricate novel metal and ceramic based biomedical implants with inbuilt antimicrobial and antiviral properties. Also, in vitro lung tissue models, especially based on 3D bioprinting technology for the screening of novel anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) therapies are also elaborated in-depth. Finally, 3DP technologies based bespoke drug delivery devices for personalized and on-demand drug dosing, complex drug release profiles, and polypills are discussed. To conclude, this chapter emphasizes the role of 3DP technologies in the development of novel emerging applications like antiviral property enriched biomedical implants, fabrication of PPE, in vitro lung tissue models, and finally personalized drug delivery devices, which could go a long way in tackling COVID-19 in an efficient manner.

This chapter deals with various biomedical applications of MXenes, from biosensing, photothermal and photodynamic anticancer therapy, combination anticancer therapy with other treatment modalities, theranostics, antimicrobial treatment platforms to more recent tissue engineering applications. The chapter throws light on the mechanistic understanding of the role of MXenes in various types of biosensors fabrication, with an emphasis on wearable sensors. The chapter also gives a detailed understanding of MXenes’ role as photothermal, photodynamic, and theranostic agents. The chapter also explicates the importance of MXenes in antimicrobial treatment and their relevance in treating antimicrobial resistance. Finally, the chapter also discusses the biocompatibility studies on MXene, which are an important aspect for MXene to have continued usage in biomedical applications. Overall, this chapter gives an overview of various biomedical applications and the relevance of MXenes in each of these applications.

Cardiovascular diseases are a leading cause of mortality across the globe, and transplant surgeries are not always successful since it is not always possible to replace most of the damaged heart tissues, for example in myocardial infarction. Chitosan, a natural polysaccharide, is an important biomaterial for many biomedical and pharmaceutical industries. Based on the origin, degree of deacetylation, structure, and biological functions, chitosan has emerged for vital tissue engineering applications. Recent studies reported that chitosan coupled with innovative technologies helped to load or deliver drugs or stem cells to repair the damaged heart tissue not just in a myocardial infarction but even in other cardiac therapies. Herein, we outlined the latest advances in cardiac tissue engineering mediated by chitosan overcoming the barriers in cardiac diseases. We reviewed in vitro and in vivo data reported dealing with drug delivery systems, scaffolds, or carriers fabricated using chitosan for stem cell therapy essential in cardiac tissue engineering. This comprehensive review also summarizes the properties of chitosan as a biomaterial substrate having sufficient mechanical stability that can stimulate the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering.

Polymeric hydrogels are widely explored materials for biomedical applications. However, they have inherent limitations like poor resistance to stimuli and low mechanical strength. This drawback of hydrogels gave rise to ‘’smart self-healing hydrogels’’ which autonomously repair themselves when ruptured or traumatized. It is superior in terms of durability and stability due to its capacity to reform its shape, injectability, and stretchability thereby regaining back the original mechanical property. This review focuses on various self-healing mechanisms (covalent and non-covalent interactions) of these hydrogels, methods used to evaluate their self-healing properties, and their applications in wound healing, drug delivery, cell encapsulation, and tissue engineering systems. Furthermore, composite materials are used to enhance the hydrogel’s mechanical properties. Hence, findings of research with various composite materials are briefly discussed in order to emphasize the healing capacity of such hydrogels. Additionally, various methods to evaluate the self-healing properties of hydrogels and their recent advancements towards 3D bioprinting are also reviewed. The review is concluded by proposing several pertinent challenges encountered at present as well as some prominent future perspectives.

Cardiovascular diseases (CVDs) are one of the leading causes of mortality worldwide and a number one killer in the USA. Cell-based approaches to treat CVDs have only shown modest improvement due to poor survival, retention, and engraftment of the transplanted cells in the ischemic myocardium. Recently, tissue engineering and the use of 3D scaffolds for culturing and delivering stem cells for ischemic heart disease are gaining rapid potential. Here, we describe a protocol for the fabrication of aligned coaxial nanofibrous scaffold comprising of a polycaprolactone (PCL) core and gelatin shell. Furthermore, we describe a detailed protocol for the efficient seeding and maintenance of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on these nanofibrous scaffolds, which could have a potential application in the generation of functional “cardiac patch” for myocardial repair applications as well as an in vitro 3D cardiac tissue model to evaluate the efficacy of cardiovascular drugs and cardiac toxicities.

Human-induced pluripotent stem cells (hiPSCs) derived cardiomyocytes (hiPSC-CMs) have been explored for cardiac regeneration and repair as well as for the development of in vitro 3D cardiac tissue models. Existing protocols for cardiac differentiation of hiPSCs utilize a 2D culture system. However, the efficiency of hiPSC differentiation to cardiomyocytes in 3D culture systems has not been extensively explored. In the present study, we investigated the efficiency of cardiac differentiation of hiPSCs to functional cardiomyocytes on 3D nanofibrous scaffolds. Coaxial polycaprolactone (PCL)-gelatin fibrous scaffolds were fabricated by electrospinning and characterized using scanning electron microscopy (SEM) and fourier transform infrared (FTIR) spectroscopy. hiPSCs were cultured and differentiated into functional cardiomyocytes on the nanofibrous scaffold and compared with 2D cultures. To assess the relative efficiencies of both the systems, SEM, immunofluorescence staining and gene expression analyses were performed. Contractions of differentiated cardiomyocytes were observed in 2D cultures after 2 weeks and in 3D cultures after 4 weeks. SEM analysis showed no significant differences in the morphology of cells differentiated on 2D versus 3D cultures. However, gene expression data showed significantly increased expression of cardiac progenitor genes (ISL-1, SIRPA) in 3D cultures and cardiomyocytes markers (TNNT, MHC6) in 2D cultures. In contrast, immunofluorescence staining showed no substantial differences in the expression of NKX-2.5 and α-sarcomeric actinin. Furthermore, uniform migration and distribution of the in situ differentiated cardiomyocytes was observed in the 3D fibrous scaffold. Overall, our study demonstrates that coaxial PCL-gelatin nanofibrous scaffolds can be used as a 3D culture platform for efficient differentiation of hiPSCs to functional cardiomyocytes.

Recent advances in cardiac tissue engineering have shown that human induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) cultured in a three-dimensional (3D) micro-environment exhibit superior physiological characteristics compared with their two-dimensional (2D) counterparts. These 3D cultured hiPSC-CMs have been used for drug testing as well as cardiac repair applications. However, the fabrication of a cardiac scaffold with optimal biomechanical properties and high biocompatibility remains a challenge. In our study, we fabricated an aligned polycaprolactone (PCL)-Gelatin coaxial nanofiber patch using electrospinning. The structural, chemical, and mechanical properties of the patch were assessed by scanning electron microscopy (SEM), immunocytochemistry (ICC), Fourier-transform infrared spectroscopy (FTIR)-spectroscopy, and tensile testing. hiPSC-CMs were cultured on the aligned coaxial patch for 2 weeks and their viability [lactate dehydrogenase (LDH assay)], morphology (SEM, ICC), and functionality [calcium cycling, multielectrode array (MEA)] were assessed. Furthermore, particle image velocimetry (PIV) and MEA were used to evaluate the cardiotoxicity and physiological functionality of the cells in response to cardiac drugs. Nanofibers patches were comprised of highly aligned core-shell fibers with an average diameter of 578 ± 184 nm. Acellular coaxial patches were significantly stiffer than gelatin alone with an ultimate tensile strength of 0.780 ± 0.098 MPa, but exhibited gelatin-like biocompatibility. Furthermore, hiPSC-CMs cultured on the surface of these aligned coaxial patches (3D cultures) were elongated and rod-shaped with well-organized sarcomeres, as observed by the expression of cardiac troponin-T and α-sarcomeric actinin. Additionally, hiPSC-CMs cultured on these coaxial patches formed a functional syncytium evidenced by the expression of connexin-43 (Cx-43) and synchronous calcium transients. Moreover, MEA analysis showed that the hiPSC-CMs cultured on aligned patches showed an improved response to cardiac drugs like Isoproterenol (ISO), Verapamil (VER), and E4031, compared to the corresponding 2D cultures. Overall, our results demonstrated that an aligned, coaxial 3D cardiac patch can be used for culturing of hiPSC-CMs. These biomimetic cardiac patches could further be used as a potential 3D in vitro model for “clinical trials in a dish” and for in vivo cardiac repair applications for treating myocardial infarction.

The global pandemic of antibiotic resistance is an ever-burgeoning public health challenge, motivating the development of adjunct bactericidal therapies. Nitric oxide (NO) is a potent bioactive gas that induces a variety of therapeutic effects, including bactericidal and biofilm dispersion properties. The short half-life, high reactivity, and rapid diffusivity of NO make therapeutic delivery challenging. The goal of this work was to characterize NO-loaded microbubbles (MB) stabilized with a lipid shell and to assess the feasibility of antibacterial therapy in vitro. MB were loaded with either NO alone (NO-MB) or with NO and octafluoropropane (NO-OFP-MB) (9:1 v/v and 1:1 v/v). The size distribution and acoustic attenuation coefficient of NO-MB and NO-OFP-MB were measured. Ultrasound-triggered release of the encapsulated gas payload was demonstrated with 3-MHz pulsed Doppler ultrasound. An amperometric microelectrode sensor was used to measure NO concentration released from the MB and compared to an NO-OFP-saturated solution. The effect of NO delivery on the viability of planktonic (free living) Staphylococcus aureus (SA) USA 300, a methicillin-resistant strain, was evaluated in a 96 well-plate format. The co-encapsulation of NO with OFP increased the total volume and attenuation coefficient of MB. The NO-OFP-MB were destroyed with a clinical ultrasound scanner with an output of 2.48 MPa peak negative pressure (in situ MI of 1.34) but maintained their echogenicity when exposed to 0.02 MPa peak negative pressure (in situ MI of 0.01. The NO dose in NO-MB and NO-OFP-MB was more than 2-fold higher than the NO-OFP-saturated solution. Delivery of NO-OFP-MB increased bactericidal efficacy compared to the NO-OFP-saturated solution or air and OFP-loaded MB. These results suggest that encapsulation of NO with OFP in lipid-shelled MB enhances payload delivery. Furthermore, these studies demonstrate the feasibility and limitations of NO-OFP-MB for antibacterial applications.

Cardiovascular disease (CVD) is among the leading causes of mortality worldwide. The shortage of donor hearts to treat end-stage heart failure patients is a critical problem. An average of 3500 heart transplant surgeries are performed globally, half of these transplants are performed in the US alone. Stem cell therapy is growing rapidly as an alternative strategy to repair or replace the damaged heart tissue after a myocardial infarction (MI). Nevertheless, the relatively poor survival of the stem cells in the ischemic heart is a major challenge to the therapeutic efficacy of stem-cell transplantation. Recent advancements in tissue engineering offer novel biomaterials and innovative technologies to improve upon the survival of stem cells as well as to repair the damaged heart tissue following a myocardial infarction (MI). However, there are several limitations in tissue engineering technologies to develop a fully functional, beating cardiac tissue. Therefore, the main goal of this review article is to address the current advancements and barriers in cardiac tissue engineering to augment the survival and retention of stem cells in the ischemic heart.

Coronary heart disease (CHD) is the leading cause of death in the Unites States and globally. The administration of growth factors to preserve cardiac function after myocardial infarction (MI) is currently being explored. Basic fibroblast growth factor (bFGF), a potent angiogenic factor has poor clinical efficacy due to its short biological half-life and low plasma stability. The goal of this study was to develop bFGF-loaded polycaprolactone (PCL) microspheres for sustained release of bFGF and to evaluate its angiogenic potential. The bFGF-PCL microspheres (bFGF-PCL-MS) were fabricated using the emulsion solvent-evaporation method and found to have spherical morphology with a mean size of 4.21 ± 1.28 μm. In vitro bFGF release studies showed a controlled release for up to 30 days. Treatment of HUVECs with bFGF-PCL-MS in vitro enhanced their cell proliferation and migration properties when compared to the untreated control group. Treatment of HUVECs with release media from bFGF-PCL-MS also significantly increased expression of angiogenic genes (bFGF and VEGFA) as compared to untreated cells. The in vivo angiogenic potential of these bFGF-PCL-MS was further confirmed in rats using a Matrigel plug assay with subsequent immunohistochemical staining showing increased expression of angiogenic markers. Overall, bFGF-PCL-MS could serve as a potential angiogenic agent to promote cell survival and angiogenesis following an acute myocardial infarction.

Xenon (Xe) is a bioactive gas capable of reducing and stabilizing neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for xenon loading and ultrasound-triggered release. Microbubbles loaded with either xenon (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) (9:1 v/v) were synthesized by high-shear mixing. The size distribution and the frequency-dependent attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband acoustic attenuation spectroscopy system, respectively. The Xe dose was evaluated using gas chromatography/mass spectrometry. The total Xe doses in Xe-MB and Xe-OFP-MB were 113.1 ± 13.5 and 145.6 ± 25.5 μl per mg of lipid, respectively. Co-encapsulation of OFP increased the total xenon dose, attenuation coefficient, microbubble stability (in an undersaturated solution), and shelf life of the agent. Triggered release of gas payload was demonstrated with 6-MHz duplex Doppler and 220-kHz pulsed ultrasound. These results constitute the first step toward the use of lipid-shelled microbubbles for applications such as neuroprotection in stroke.

The development of adjuvant techniques to improve thrombolytic efficacy is important for advancing ischemic stroke therapy. We characterized octafluoropropane and recombinant tissue plasminogen activator (rt-PA)-loaded echogenic liposomes (OFP t-ELIP) using differential interference and fluorescence microscopy, attenuation spectroscopy, and electrozone sensing. The loading of rt-PA in OFP t-ELIP was assessed using spectrophotometry. Further, it was tested whether the agent shields rt-PA against degradation by plasminogen activator inhibitor-1 (PAI-1). An in vitro system was used to assess whether ultrasound (US) combined with either Definity or OFP t-ELIP enhances rt-PA thrombolysis. Human whole blood clots were mounted in a flow system and visualized using an inverted microscope. The perfusate consisted of either (1) plasma alone, (2) rt-PA, (3) OFP t-ELIP, (4) rt-PA and US, (5) OFP t-ELIP and US, (6) Definity and US, or (7) rt-PA, Definity, and US (n = 16 clots per group). An intermittent US insonation scheme was employed (220 kHz frequency, and 0.44 MPa peak-to-peak pressures) for 30 min. Microscopic imaging revealed that OFP t-ELIP included a variety of structures such as liposomes (with and without gas) and lipid-shelled microbubbles. OFP t-ELIP preserved up to 76% of rt-PA activity in the presence of PAI-1, whereas only 24% activity was preserved for unencapsulated rt-PA. The use of US with rt-PA and Definity enhanced lytic efficacy (p < 0.05) relative to rt-PA alone. US combined with OFP t-ELIP enhanced lysis over OFP t-ELIP alone (p < 0.01). These results demonstrate that ultrasound combined with Definity or OFP t-ELIP can enhance the lytic activity relative to rt-PA or OFP t-ELIP alone, respectively.

We demonstrate facile and green synthesis of gold deposited zein nanoshells (AuZNS) using environmental benign solvent ethanol. Water soluble glycol chitosan is used for stabilization as well as for cationic functionalization of zein nanoparticles. Gold deposition is performed via ex-situ method at ambient conditions. AuZNS is of size around 100 nm and shows high inertness and biocompatibility even at double the therapeutic dosage. The absorbance is tuned at 808 nm for imaging-guided plasmonic photothermal therapy of cancer. Highly effective killing of cancer cells irrespective of their chemorefractory status is noticed at a very low therapeutic dosage of 25 μg and 5 min of biologically acceptable (500 mW) 808 nm laser irradiation. AuZNS also exhibit better X-ray attenuation in comparison to the commercially available iodine based contrast agent.

Modification of dissolved gas content by acoustic droplet vaporization (ADV) has been proposed for several therapeutic applications. Reducing dissolved oxygen (DO) during reperfusion of ischemic tissue during coronary interventions could inhibit reactive oxygen species production and rescue myocardium. The objective of this study was to determine whether intravascular ultrasound (IVUS) can trigger ADV and reduce DO. Perfluoropentane emulsions were created using highspeed shaking and microfluidic manufacturing. High-speed shaking resulted in a polydisperse droplet distribution ranging from less than 1 micron to greater than 16 microns in diameter. Microfluidic manufacturing produced a narrower size range of droplets with diameters between 8.0 microns and 9.6 microns. The DO content of the fluids was measured before and after ADV triggered by IVUS exposure. Duplex B-mode and passive cavitation imaging was performed to assess nucleation of ADV. An increase in echogenicity indicative of ADV was observed after exposure with a clinical IVUS system. In a flow phantom, a 20% decrease in DO was measured distal to the IVUS transducer when droplets, formed via high-speed shaking, were infused. In a static fluid system, the DO content was reduced by 11% when droplets manufactured with a microfluidic chip were exposed to IVUS. These results demonstrate that a reduction of DO by ADV is feasible using a clinical IVUS system. Future studies will assess the potential therapeutic efficacy of IVUS-nucleated ADV and methods to increase the magnitude of DO scavenging.

Surgical intervention of the solid tumours is the most preferred cancer treatment strategy in the current scenario. But, the main issue is that there is always a probability of resurrection of tumor due to the fact that not all cancer cells can be removed completely. In order to overcome this, controlled delivery of the therapeutic agents into the tumor region after the surgical removal of tumor seems to be a viable option. We developed a composite injectable Chitosan gel (DZ-CGs) comprising of Doxorubicin loaded Zein nanoparticles (DOX-SC ZNPs) which flows (in their sol state) and can take up the exact shape of the void (created by the surgical removal of the tumor) and becomes gel (at physiological temperature). DOX-SC ZNPs were synthesized by anti-solvent nano-precipitation method. The size and zeta potential of DOX-SC ZNPs were found to be 120 ± 16 nm and −26.97 mV respectively. In vitro drug release profiles of DZ-CGs were found to be more controlled when compared to DOX-SC ZNPs. In vitro cyto-toxicity studies of DOX-SC ZNPs and DZ-CGs were compared on human breast cancer cell lines using Transwell insert method and found that composite DZ-CGs were more effective in killing cancer cells when compared to DOX-SC ZNPs.

With the onset of hyperthermia and their advantage in increasing vascular perfusion and permeability in the cancer milieu, thermo-responsive polymers have become an attractive candidate for designing therapeutic nano-vehicles for targeted on-demand delivery of bioactive agents. For this purpose, we developed a dual (thermo- and pH-) responsive nanotherapeutic composite system rendering a combinational therapy of hyperthermia mediated drug delivery. This composite system comprises of magnetic chitosan-g-PNVCL (MCP) polymeric nanogels loaded with anticancer drug, Doxorubicin (DOX). The size distribution and the stability of the MCP nanogels have been characterized using DLS and Zeta-potential studies. XRD and TG-DTA confirms the presence of magnetic nanoparticles loaded onto MCP nanogel. ICP-AES analysis was done to determine the amount of iron content in the MCP nanogels. The magnetic property of the MCP nanogels was estimated to be ∼37 emu/g using Vibrating Sample Magnetometer (VSM). The heating ability of MCP nanogels was calculated to be ∼204 W/g for the concentration of 2 mg/mL using time-dependent Specific Absorption Rate (SAR) method. Magnetic field induced thermo-responsive and pH responsive drug release studies were carried out and it was found that MCP nanogels have a good on-demand drug release properties. The DOX-MCP nanogels were evaluated for its in vitro killing efficacy of breast cancer cells MCF 7 and MDAMB 231 cells with synergistic effects of both hyperthermia and chemotherapy in presence of magnetic field at the concentration of 2 mg/mL. Thus, MCP nanogels can be a potential dual modal on-demand hyperthermia mediated drug delivery platform for the breast cancer treatment.

The main aim of this work is to design a heat triggered transdermal drug delivery system (TDDS) using a thermoresponsive polymer, poly (N-vinyl caprolactam) [PNVCL] based gel, where in patients can themselves administer a pulse of drug on mere application of heat pad over the TDDS, whenever pain is experienced. The phase transition temperature of PNVCL was tuned to 35°C by grafting it onto a pH sensitive biopolymer, Chitosan, to synthesize Chitosan-g-PNVCL (CP) co-polymer which render the gel both thermo- and pH-responsive property. The application of triggered delivery was explored by loading acetamidophenol (a model hydrophilic drug) and etoricoxib (a model hydrophobic drug). In vitro drug release experiments were performed at three different temperatures (25, 32 and 39°C) at two different pH (5.5 and 7) to study its drug release with response to temperature and pH. Drug release profiles obtained were found to have enhanced release for both the drugs respectively at 39°C (above LCST) and pH 5.5 when compared to other release conditions. In vitro skin permeation of both the drugs performed in rat abdominal skin using Franz diffusion cell showed enhanced drug release when the skin was subjected to higher temperature (39°C). Moreover, it was also found that skin permeation for hydrophobic drug was better than that of hydrophilic drug. The in vivo biocompatibility studies of the CP gel in rat skin proved that the gel is biocompatible. The results obtained demonstrated the potential use of the thermoresponsive CP gel as an on-demand localized drug delivery system.

This study aimed to evaluate Poly (caprolactone) microparticles (MPs) loaded composite injectable Chitosan gel (CICGs) as a dual purpose (visco-supplement and intra articular drug delivery depot) therapeutic agent for the treatment of Osteoarthritis. Etoricoxib (COX-2 inhibitor), a highly hydrophobic drug was chosen as a model drug for the study. When administered orally, Etoricoxib poses severe cardiovascular toxicity issues. So, we have attempted to deliver this drug intra-articularly, which could retain the drug longer in the joint region and thus could ameliorate these toxicity issues. CICGs were prepared by dispersing MPs in the chitosan-Ammonium hydrogen phosphate solution and incubated at 37 °C. Rheology studies proved that gels were stable and had visco-elastic properties comparable to that of existing visco-supplements. The in vitro drug release profiles of CICGs were found to be more controlled when compared to MPs and bare chitosan gel (BCGs). In vitro and in vivo biocompatibility studies proved that the gels were biocompatible. In vivo synovial drug clearance studies proved that CICGs had a better drug retention capacity than BCGs and MPs. In vivo fluorescence imaging results confirmed that CICGs could stay longer in the joint region when compared to BCGs and MPs. Thus this novel CICGs could be a potential dual purpose gel for the treatment of diseased joint regions especially for Osteoarthritis.

Intra-articular Drug delivery systems (IA-DDS) deliver the drug directly to the diseased joint space with significantly lowered systemic toxicities. In this work, we explored Etoricoxib (COX-2 inhibitor)-loaded Poly caprolactone (PCL) microparticles (MPs) as a potential IA-DDS. MPs were prepared by Oil/Water (O/W) emulsion-solvent evaporation method. Formulation parameters like polymer to drug ratio, stabilizer concentration were optimized to get the maximum encapsulation efficiency. The prepared particles were characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction studies (XRD), and Differential Scanning Calorimetry (DSC). The particles were found to be spherical and smooth-surfaced using SEM. FTIR studies proved that there was no chemical interaction between the drug and the polymer. XRD and DSC studies confirmed that Etoricoxib existed in its amorphous form while PCL had retained its semi-crystalline phase during the micro-encapsulation process. In vitro drug release studies proved that there was controlled release of the drug from the MPs for nearly 28 days. In vivo synovial drug clearance studies on SD rats proved that drug leach out rate from the joint region to the systemic circulation was slow which indicated that MPs had a good drug retention capacity. In vivo fluorescence imaging results confirmed that MPs could stay longer in the joint region for almost a month. Thus, PCL microparticles could be a potential IA-DDS for the treatment of the diseased joint regions especially for Osteoarthritis.

Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co- glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy. Copyright © 2014 American Scientific Publishers All rights reserved.