Lecithin Organogel: A Promising Carrier for the Treatment of Skin Diseases.

Skin is the largest organ of the human body, as it protects the body from the external environment. Nowadays, skin diseases and skin problems are more common, and millions of people are affected daily. Skin diseases are due to numerous infectious pathogens or inflammatory conditions. The increasing demand for theoretical research and practical applications has led to the rising prominence of gel as a semisolid material. To this end, organogels has been widely explored due to their unique composition, which includes organic solvents and mineral or vegetable oils, among others. Organogels can be described as semisolid systems wherein an organic liquid phase is confined within a three-dimensional framework consisting of self-assembled, cross-linked, or entangled gelator fibers. These gels have the ability to undergo significant expansion and retain substantial amounts of the liquid phase, reaching up to 99% swelling capacity. Furthermore, they respond to a range of physical and chemical stimuli, including temperature, light, pH, and mechanical deformation. Notably, due to their distinctive properties, they have aroused significant interest in a variety of practical applications. Organogels favor the significant encapsulation and enhanced permeation of hydrophobic molecules when compared with hydrogels. Accordingly, organogels are characterized into lecithin organogels, pluronic lecithin organogels, sorbitan monostearate-based organogels, and eudragit organogels, among others, based on the nature of their network and the solvent system. Lecithin organogels contain lecithin (natural and safe as a living cell component) as an organogelator. It acts as a good penetration enhancer. In this review, first we have summarized the fundamental concepts related to the elemental structure of organogels, including their various forms, distinctive features, methods of manufacture, and diverse applications. Nonetheless, this review also sheds light on the delivery of therapeutic molecules entrapped in the lecithin organogel system into deep tissue for the management of skin diseases and provides a synopsis of their clinical applications.

Poly(d,l-lactide-co-glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer.

A poly(d,l-lactide-co-glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance-Fourier transform infrared, 1H and 13C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log p < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log p < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers' nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin.

Polyelectrolyte-Complex-Based Hydrogel Inserts for Vaginal Delivery of Posaconazole and Probiotics.

Worldwide, 40 to 50% of women suffer from reproductive tract infections. Most of these infections are mixed infections, are recurrent and difficult to treat with antimicrobials or antifungals alone. For symptomatic relief of infections, oral antimicrobial therapy must be combined with topical therapy. The purpose of this work is to optimize and develop a polyelectrolyte complex (PEC) of chitosan/anion for the formulation of posaconazole- and probiotic-loaded vaginal hydrogel inserts with prolonged release and significant mucoadhesion. PECs were prepared using chitosan as cationic and carrageenan, pectin and polycarbophil as anionic polymers via a lyophilization technique. PEC formation was confirmed by scanning electron microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry, by observing changes in its surface, physical and thermal properties. The probiotic, Lactobacillus casei, was added to the PEC during the lyophilization process and the effect on the probiotic viability was studied. The PECs were further compressed along with posaconazole to form hydrogel inserts and optimized using a 32 full-factorial design. The hydrogel inserts were assessed for swelling behavior, drug release, in vitro mucoadhesion and in vitro antifungal activity. The chitosan-pectin hydrogel insert demonstrated excellent mucoadhesion (1.25 N), sustained drug release (88.2 ± 2.4% in 8 h) and a swelling index of 154.7%. The efficacy of hydrogel inserts was evaluated using in vitro study with a co-culture of Lactobacillus casei and Candida albicans. This study revealed an increase in Lactobacilli casei count and a significant drop in the viable count of Candida albicans (4-log reduction in 24 h), indicating the effectiveness of hydrogel inserts in alleviating the fungal infection. Overall, our study demonstrated the potential of the hydrogel insert for preventing vaginal infection and restoring normal vaginal microbiota.

Formulation Development and Evaluation of Indian Propolis Hydrogel for Wound Healing.

Flavonoids and polyphenolic compounds play a key role in wound healing cycle modulation. Propolis, a natural bee product, has been widely reported as an enriched source of polyphenols and flavonoids as important chemical constituents and for its wound healing potential. The goal of this study was to develop and characterize a propolis-based polyvinyl alcohol (PVA) hydrogel composition with wound healing potential. To understand the impacts of critical material attributes and process parameters, formulation development was carried out using a design of experiment approach. A preliminary phytochemical analysis of Indian propolis extract showed the presence of flavonoids (23.61 ± 0.0452 mg equivalent of quercetin/g) and polyphenols (34.82 ± 0.0785 mg equivalent of gallic acid/g), both of which aid in wound healing and skin tissue regeneration. The pH, viscosity, and in vitro release of the hydrogel formulation were also studied. The burn wound healing model results revealed significant (p < 0.0001) wound contraction by propolis hydrogel (93.58 + 0.15%) with rapid re-epithelialization relative to 5% w/w povidone iodine ointment USP (Cipladine®) (95.39 + 0.16%). The excision wound healing model confirms significant (p < 0.0001) wound contraction by propolis hydrogel (91.45 + 0.29%) with accelerated re-epithelialization comparable to 5% w/w povidone iodine ointment USP (Cipladine®) (94.38 + 0.21%). The developed formulation offers promise for wound healing, which may be investigated further for clinical research.

A Systematic Overview of Eudragit® Based Copolymer for Smart Healthcare.

Eudragit, synthesized by radical polymerization, is used for enteric coating, precise temporal release, and targeting the entire gastrointestinal system. Evonik Healthcare Germany offers different grades of Eudragit. The ratio of methacrylic acid to its methacrylate-based monomers used in the polymerization reaction defines the final product's characteristics and consequently its potential range of applications. Since 1953, these polymers have been made to use in a wide range of healthcare applications around the world. In this review, we reviewed the "known of knowns and known of unknowns" about Eudragit, from molecule to material design, its characterization, and its applications in healthcare.

Herbal-Based Dressings in Wound Management.

Wound management is one of the major global challenges in recent times, and woundassociated infection has a significant impact on the healthcare economy worldwide. Wounds can be acute or chronic type, also diabetic, trauma, accidental, burn wounds and minor cuts, bruises, and rashes, etc. One of the primary treatment options available in these conditions are the use of suitable dressing materials to cover the wound and accelerate the healing process. Since ancient times, according to archaeological theories, medicinal plants and oils have been employed for the treatment of wounds. Today researchers across the globe are focusing their efforts on fabrication of novel dressing materials that can provide the most effective treatment, easy exchange of nutrients, and absorb exudate from the wounds. Very lately, various research groups are also concentrating on the design and development of herb-loaded wound dressings, as herbal preparations contain numerous phytoconstituents with a broad spectrum of pharmacological properties when compared to synthetic drugs and also due to the perceived notion that herbal products are generally safe, even when administered over prolonged periods. They contain numerous bioactive that can act on the various phases of the wound healing process, providing an ideal environment for the healing process. The present review discusses the numerous approaches that are employed for the preparation of dressing materials incorporated with plant-derived phytoconstituents/extracts. This review also provides an insight into the healing process and wound healing agents derived from medicinal plants and oils. The review can serve as a database for researchers working in this field and can help them to select the most appropriate dressing material for the effective delivery of herbal preparations in the management of wounds.

Photodynamic Therapy for Bladder Cancers, A Focused Review†.

Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non-muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.

Cyclodextrin-based dermatological formulations: Dermopharmaceutical and cosmetic applications.

The progress in new delivery systems for active ingredients has boosted the dermopharmaceutical and cosmetic fields by allowing formulations to display enhanced skin permeation capabilities. Cyclodextrins (CDs) are cyclic oligosaccharides able to form host-guest inclusion complexes with guest active molecules, resulting in improved physicochemical properties of such molecules. The incorporation of CDs in dermopharmaceutical and cosmetics formulations has received much attention since the late 1970 s by enhancing modulation of the passage through the skin and vectorization into the target site while simultaneously offering a biocompatible delivery system. This paper features the advantages of CDs in dermopharmaceutical and cosmetic applications, such as the improvement of the apparent solubility and the stability of the active ingredients, the possibility of masking unpleasant odors, among others that are be described, emphasizing that these versatile skin active ingredient carriers are strongly promising both in the treatment of skin diseases and in the improvement of cosmetic formulations.

Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations.

The surface drying process is an important technology in the pharmaceutical, biomedical, and food industries. The final stage of formulation development (i.e., the drying process) faces several challenges, and overall mastering depends on the end step. The advent of new emerging technologies paved the way for commercialization. Thin film freezing (TFF) is a new emerging freeze-drying technique available for various treatment modalities in drug delivery. TFF has now been used for the commercialization of pharmaceuticals, food, and biopharmaceutical products. The present review highlights the fundamentals of TFF along with modulated techniques used for drying pharmaceuticals and biopharmaceuticals. Furthermore, we have covered various therapeutic applications of TFF technology in the development of nanoformulations, dry powder for inhalations and vaccines. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia.

Surface Functionalization of Nanofibers: The Multifaceted Approach for Advanced Biomedical Applications.

Nanocarriers are gaining significant importance in the modern era of drug delivery. Nanofiber technology is one of the prime paradigms in nanotechnology for various biomedical and theranostic applications. Nanofibers obtained after successful electrospinning subjected to surface functionalized for drug delivery, biomedical, tissue engineering, biosensing, cell imaging and wound dressing application. Surface functionalization entirely changes physicochemical and biological properties of nanofibers. In physicochemical properties, wettability, melting point, glass transition temperature, and initial decomposition temperature significantly change offer several advantageous for nanofibers. Similarly, biological properties include cell adhesion, biocompatibility, and proliferation, also changes by functionalization of nanofibers. Various natural and synthetic materials polymers, metals, carbon materials, functional groups, proteins, and peptides, are currently used for surface modification of nanofibers. Various research studies across the globe demonstrated the usefulness of surface functionalized nanofibers in tissue engineering, wound healing, skin cancers, melanoma, and disease diagnosis. The delivery of drug through surface functionalized nanofibers results in improved permeation and bioavailability of drug which is important for better targeting of disease and therapeutic efficacy. This review provides a comprehensive insight about various techniques of surface functionalization of nanofibers along with its biomedical applications, toxicity assessment and global patent scenario.

An overview: CRISPR/Cas-based gene editing for viral vaccine development.

INTRODUCTION: Gene-editing technology revolutionized vaccine manufacturing and offers a variety of benefits over traditional vaccinations, such as improved immune response, higher production rate, stability, precise immunogenic activity, and fewer adverse effects. The more recently discovered Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/associated protein 9 (Cas9) system has become the most widely utilized technology based on its efficiency, utility, flexibility, versatility, ease of use, and cheaper compared to other gene-editing techniques. Considering its wider scope for genomic modification, CRISPR/Cas9-based technology's potential is explored for vaccine development. AREAS COVERED: In this review, we will address the recent advances in the CRISPR/Cas system for the development of vaccines and viral vectors for delivery. In addition, we will discuss strategies for the development of the vaccine, as well as the limitations and future prospects of the CRISPR/Cas system. EXPERT OPINION: Human and animal viruses have been exposed to antiviral CRISPR/Cas9-based engineering to prevent infection, which uses knockout, knock-in, gene activation/deactivation, RNA targeting, and editing cell lines strategies for gene editing of viruses. Because of that CRISPR/Cas system is used to boost the vaccine production yield by removing unwanted genes that cause disease or are required for viral infection.

A Comparative Study of Quercetin-Loaded Nanocochleates and Liposomes: Formulation, Characterization, Assessment of Degradation and In Vitro Anticancer Potential.

Quercetin, a flavonoid, has antioxidant and anti-inflammatory properties and the potential to inhibit the proliferation of cancer, but its therapeutic efficacy is lowered due to poor solubility and bioavailability. Quercetin-loaded nanocochleates (QN) were developed using a trapping method by the addition of calcium ions into preformed negatively charged liposomes (QL) prepared by a thin-film hydration method. Liposomes were optimized by varying the concentration of Dimyristoyl phosphatidyl glycerol and quercetin by applying D-optimal factorial design using Design-Expert® software. Stable rods were observed using TEM with an average particle size, zeta potential and encapsulation efficiency of 502 nm, -18.52 mV and 88.62%, respectively, for QN which were developed from spherical QL showing 111.06 nm, -40.33 mV and 74.2%, respectively. In vitro release of quercetin from QN and QL was extended to 24 h. Poor bioavailability of quercetin is due to its degradation in the liver, so to mimic in vivo conditions, the degradation of quercetin released from QL and QN was studied in the presence of rat liver homogenate (S9G) and results revealed that QN, due to its unique structure, i.e., series of rolled up solid layers, shielded quercetin from the external environment and protected it. The safety and biocompatibility of QL and QN were provenby performing cytotoxicity studies on fibroblast L929 cell lines. QN showed superior anticancer activity compared to QL, as seen for human mouth cancerKB cell lines. Stability studies proved that nanocochleates were more stable than liposomal formulations. Thus, nanocochleates might serve as pharmaceutical nanocarriers for the improved efficacy of drugs with low aqueous solubility, poor bioavailability, poor targeting ability and stability.

Functional Thermoresponsive Hydrogel Molecule to Material Design for Biomedical Applications.

Temperature-induced, rapid changes in the viscosity and reproducible 3-D structure formation makes thermos-sensitive hydrogels an ideal delivery system to act as a cell scaffold or a drug reservoir. Moreover, the hydrogels' minimum invasiveness, high biocompatibility, and facile elimination from the body have gathered a lot of attention from researchers. This review article attempts to present a complete picture of the exhaustive arena, including the synthesis, mechanism, and biomedical applications of thermosensitive hydrogels. A special section on intellectual property and marketed products tries to shed some light on the commercial potential of thermosensitive hydrogels.

Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications.

Microneedle (MNs) technology is a recent advancement in biomedical science across the globe. The current limitations of drug delivery, like poor absorption, low bioavailability, inadequate skin permeation, and poor biodistribution, can be overcome by MN-based drug delivery. Nanotechnology made significant changes in fabrication techniques for microneedles (MNs) and design shifted from conventional to novel, using various types of natural and synthetic materials and their combinations. Nowadays, MNs technology has gained popularity worldwide in biomedical research and drug delivery technology due to its multifaceted and broad-spectrum applications. This review broadly discusses MN's types, fabrication methods, composition, characterization, applications, recent advancements, and global intellectual scenarios.

Comprehensive Review on the Degradation Chemistry and Toxicity Studies of Functional Materials.

In recent decades there has been growing interest of material chemists in the successful development of functional materials for drug delivery, tissue engineering, imaging, diagnosis, theranostic, and other biomedical applications with advanced nanotechnology tools. The efficacy and safety of functional materials are determined by their pharmacological, toxicological, and immunogenic effects. It is essential to consider all degradation pathways of functional materials and to assess plausible intermediates and final products for quality control. This review provides a brief insight into chemical degradation mechanisms of functional materials like oxidation, photodegradation, and physical and enzymatic degradation. The intermediates and products of degradation were confirmed with analytical methods such as proton nuclear magnetic resonance (1H NMR), gel permeation chromatography (GPC), UV-vis spectroscopy (UV-vis), infrared spectroscopy (IR), differential scanning calorimetry (DSC), mass spectroscopy, and other sophisticated analytical methods. These analytical methods are also used for regulatory, quality control, and stability purposes in industry. The assessment of degradation is important to predetermine the behavior of functional materials in specific storage conditions and can be relevant to their behavior during in vivo applications. Another important aspect is the evaluation of the toxicity of functional materials. Toxicity can be accessed with various methods using in vitro, in vivo, ex vivo, and in silico models. In vitro cell culture methods are used to determine mitochondrial damage, reactive oxygen species, stress responses, and cellular toxicity. In vitro cellular toxicity can be measured by MTT assay, LDH leakage assay, and hemolysis. In vivo studies are performed using various animal models involving zebrafish, rodents (mice and rats), and nonhuman primates. Ex vivo studies are also used for efficacy and toxicity determinations of functional materials like ex vivo potency assay and precision-cut liver slice (PCLS) models. The in silico tools with computational simulations like quantitative structure-activity relationships (QSAR), pharmacokinetics (PK) and pharmacodynamics (PD), dose and time response, and quantitative cationic-activity relationships ((Q)CARs) are used for prediction of the toxicity of functional materials. In this review, we studied the principle methods used for degradation studies, different degradation pathways, and mechanisms of functional material degradation with prototype examples. We discuss toxicity assessments with different toxicity approaches used for estimation of the safety and efficacy of functional materials.

Green synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactide-co-glycolide) copolymer using zinc proline as a biocompatible initiator for irinotecan delivery to colon cancer in vivo.

Poly(lactic-co-glycolic acid) (PLGA) is the most commonly described biocompatible copolymer used in biomedical applications. In this work, a green synthetic approach based on the biocompatible zinc proline complex, as an initiator for PLGA synthesis, is reported for the first time for the synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactic-co-glycolic acid) (mPEG-PLGA). mPEG-PLGA with controlled molecular weight and narrow polydispersity was synthesised. Its potential for delivery of irinotecan (Ir), a poorly water-soluble chemotherapeutic drug used for the treatment of colon and pancreatic cancer, was studied. Nanoparticles of controlled size (140-160 nm), surface charge (∼-10 mV), release properties and cytotoxicity against CT-26 (colon) and BxPC-3 (pancreatic) cancer cells, were prepared. Tumor accumulation was confirmed by optical imaging of fluorescently labelled nanoparticles. Unlike Tween® 80 coated NP-Ir, the Pluronic® F-127 coated NP-Ir exhibits significant tumor growth delay compared to untreated and blank formulation treated groups in the CT-26 subcutaneous tumor model, after 4 treatments of 30 mg irinotecan per kg dose. Overall, this proof-of-concept study demonstrates that the newly synthesized copolymer, via a green route, is proven to be nontoxic, requires fewer purification steps and has potential applications in drug delivery.

LHRH-conjugated, PEGylated, poly-lactide-co-glycolide nanocapsules for targeted delivery of combinational chemotherapeutic drugs Docetaxel and Quercetin for prostate cancer.

One of the major challenges in effective cancer chemotherapy is the severe systemic cytotoxicities of anticancer drugs on healthy tissues. The present study reports chemically modified polymeric nanocapsules (NCs) encapsulating combination of chemotherapeutic drugs Docetaxel (DTX) and Quercetin (QU) for its active targeting to prostate cancer (PCa). The active targeting was achieved by conjugating Luteinizing-hormone-releasing hormone (LHRH) ligand to poly-lactide-co-glycolide (PLGA) using polyethylene glycol (PEG) as a spacer. The structure of the conjugates was characterized and confirmed using 1H NMR and ATR-FTIR. The drug encapsulated NCs showed a homogenous size distribution with their size ranging between 120 and 150 nm, and exhibited a negative zeta potential in the range of -20 to -40 mV. The in vitro release studies highlighted the sustained drug release pattern from the respective NCs; while the PEG coating to polymeric NCs provided serum stability to the NCs. The in vitro biological evaluation of the NCs was conducted using PC-3 and LNCaP cell lines. The results of the cellular uptake studies showed a significantly higher untake of the LHRH targeted NCs, while the LHRH-targeted-PEGylated DTX: QU NCs exhibited higher caspase-3 activity. The cell viability assay results showed the enhanced cell inhibition activity of the combinatorial DTX: QU when compared to individual DTX. Further, higher cell cytotoxicity was achieved by LHRH-targeted DTX: QU NCs as compared to their free-form or non-targeted NCs. Finally, the results of in vivo tumor localization and in vivo antitumor activity studies complimented and upheld the in vitro results, demonstrating the beneficial role of PLGA-PEG-LHRH NCs encapsulating combination of DTX and QU in combating prostate cancer (PCa).

Poly (vinylpyrrolidone)­iodine engineered poly (ε-caprolactone) nanofibers as potential wound dressing materials.

Facilitating the process of wound healing and effective treatment of wounds remains a serious challenge in healthcare. Wound dressing materials play a major role in the protection of wounds and in accelerating the natural healing process. In the present study, novel core/shell (c/s) nanofibrous mats of poly(vinyl pyrrolidone)­iodine (PVPI) and polycaprolactone (PCL) were fabricated using a co-axial electrospinning process followed by their surface modification with poly-l-lysine. The developed nanofibrous mats were extensively characterized for their physicochemical properties using various analytical techniques. The core/shell structure of the PVP-I/PCL nanofibers was confirmed using TEM analysis. The PVP-I release studies showed an initial burst phase followed by a sustained release pattern of PVP-I over a period of 30 days. The developed nanofibers exhibited higher BSA and fibrinogen adsorption as compared to pristine PCL. Cytotoxicity studies using MTT assay demonstrated that the PVP-I/PCL (c/s) nanofibers were cytocompatible at optimized PVP-I concentration (3 wt%). The PCL-poly-l-lysine and PVP-I/PCL-poly-l-lysine nanofibers exhibited higher cell viability (24.2% and 21.4% higher at day 7) when compared to uncoated PCL and PVP-I/PCL nanofibers. The PVP-I/PCL nanofibers showed excellent antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. The inflammatory response of Mouse RAW 264.7 macrophage cells towards the nanofibers was studied using RT-PCR. It revealed that the pro-inflammatory cytokines (TNF-α and IL-1ß) were significantly upregulated on PCL nanofibers, while their expression was comparatively lower on poly-l-lysine coated PCL or PVP-I/PCL(c/s) nanofibers. Overall, the study highlights the ability of poly-l-lysine coated PVP-I/PCL (c/s) nanofibers as potential wound dressing materials effectively facilitating the early stage wound healing and repair process by virtue of their selective modulation of inflammation, cell adhesion and antimicrobial properties.

Electrospun polycaprolactone/hydroxyapatite/ZnO nanofibers as potential biomaterials for bone tissue regeneration.

Fabricating a bioartificial bone graft possessing structural, mechanical and biological properties mimicking the real bone matrix is a major challenge in bone tissue engineering. Moreover, the developed materials are prone to microbial invasion leading to biomaterial centered infections which might limit their clinical translation. In the present study, biomimetic nanofibrous scaffolds of Poly ɛ-caprolactone (PCL)/nano-hydroxyapatite (nHA) were electrospun with 1wt%, 5wt%, 10wt%, 15wt% and 30wt% of zinc oxide (ZnO) nanoparticles in order to understand the optimal concentration range of (ZnO) nanoparticles balancing both biocompatibility and osteoregeneration. The developed nanofibrous scaffolds were successfully characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDAX), contact angle, fourier transform infrared spectroscopy (FTIR), wide-angle X-Ray diffraction (WAXD), brunaueremmett Teller (BET) surface area and tensile testing. Biocompatibility of the developed scaffolds at in vitro level was evaluated by culturing MG-63 cells and investigating the impact on cell viability, proliferation, protein adsorption, alkaline phosphatase (ALP) activity and biomineralization. The PCL/nHA scaffolds exhibited a 1.2-fold increase in cell viability and proliferation, while incorporation of ZnO nanoparticles to PCL/nHA imparted antimicrobial activity to the scaffolds with a progressive increase in the antimicrobial efficacy with increasing ZnO concentration. The results of cell viability were supported by ALP activity and mineralization assay, wherein, PCL/nHA/ZnO scaffolds showed higher ALP activity and better mineralization capacity as compared to pristine PCL. Although, the PCL/nHA/ZnO scaffolds with 10, 15 and 30wt% of ZnO particles exhibited superior antimicrobial efficacy against both gram-negative (E. coli) and gram-positive (S. aureus) bacteria, a significant decrease in the cell viability and mechanical properties was observed at higher concentrations of ZnO namely 15 and 30%. Amongst the various ZnO concentrations studied optimal cell viability, antimicrobial effect and mechanical strength were observed at 10wt.% ZnO concentration. Thus, the present study revealed that the biomimetic tri-component PCL/nHA/ZnO scaffolds with ZnO concentration range of ≤ 10% could be ideal for achieving optimal biocompatibility (cell proliferation, biomineralization, and antimicrobial capacity) and mechanical stability thus making it a promising biomaterial substrate for bone tissue regeneration.

Clopidogrel eluting electrospun polyurethane/polyethylene glycol thromboresistant, hemocompatible nanofibrous scaffolds.

Biomaterials used as blood-contacting material must be hemocompatible and exhibit lower thrombotic potential while maintaining hemostasis and angiogenesis. With the aim of developing thromboresistant, hemocompatible nanofibrous scaffolds, polyurethane/polyethylene glycol scaffolds incorporated with 1, 5, and 10 wt% Clopidogrel were fabricated and evaluated for their physiochemical properties, biocompatibility, hemocompatibility, and antithrombotic potential. The results of physicochemical characterization revealed the fabrication of nanometer-sized scaffolds with smooth surfaces. The incorporation of both polyethylene glycol and Clopidogrel to polyurethane enhanced the hydrophilicity and water uptake potential of polyurethane/polyethylene glycol/Clopidogrel scaffolds. The dynamic mechanical analysis revealed the enhancement in mechanical strength of the polyurethane/polyethylene glycol scaffolds on incorporation of Clopidogrel. The polyurethane/polyethylene glycol/Clopidogrel scaffolds showed a tri-phasic drug release pattern. The results of hemocompatibility assessment demonstrated the excellent blood compatibility of the polyurethane/polyethylene glycol/Clopidogrel scaffolds, with the developed scaffolds exhibiting lower hemolysis, increased albumin and plasma protein adsorption while reduction in fibrinogen adsorption. Further, the platelet adhesion was highly suppressed and significant increase in coagulation period was observed for Clopidogrel incorporated scaffolds. The results of cell adhesion and cell viability substantiate the biocompatibility of the developed nanofibrous scaffolds with the HUVEC cell viability on polyurethane/polyethylene glycol, polyurethane/polyethylene glycol/Clopidogrel-1, 5, and 10% at day 7 found to be 12.35, 13.36, 14.85, and 4.18% higher as compared to polyurethane scaffolds, and the NIH/3T3 cell viability found to be 35.27, 70.82, 36.60, and 7.95% higher as compared to polyurethane scaffolds, respectively. Altogether the results of the study advocate the incorporation of Clopidogrel to the polyurethane/polyethylene glycol blend in order to fabricate scaffolds with appropriate antithrombotic property, hemocompatibility, and cell proliferation capacity and thus, might be successfully used as antithrombotic material for biomedical application.