Development and comparison of machine learning models for in-vitro drug permeation prediction from microneedle patch.

The field of machine learning (ML) is advancing to a larger extent and finding its applications across numerous fields. ML has the potential to optimize the development process of microneedle patch by predicting the drug release pattern prior to its fabrication and production. The early predictions could not only assist the in-vitro and in-vivo experimentation of drug release but also conserve materials, reduce cost, and save time. In this work, we have used a dataset gleaned from the literature to train and evaluate different ML models, such as stacking regressor, artificial neural network (ANN) model, and voting regressor model. In this study, models were developed to improve prediction accuracy of the in-vitro drug release amount from the hydrogel-type microneedle patch and the in-vitro drug permeation amount through the micropores created by solid microneedles on the skin. We compared the performance of these models using various metrics, including R-squared score (R2 score), root mean squared error (RMSE), and mean absolute error (MAE). Voting regressor model performed better with drug permeation percentage as an outcome feature having RMSE value of 3.24. In comparison, stacking regressor have a RMSE value of 16.54, and ANN model has shown a RMSE value of 14. The value of permeation amount calculated from the predicted percentage is found to be more accurate with RMSE of 654.94 than direct amount prediction, having a RMSE of 669.69. All our models have performed far better than the previously developed model before this research, which had a RMSE of 4447.23. We then optimized voting regressor model's hyperparameter and cross validated its performance. Furthermore, it was deployed in a webapp using Flask framework, showing a way to develop an application to allow other users to easily predict drug permeation amount from the microneedle patch at a particular time period. This project demonstrates the potential of ML to facilitate the development of microneedle patch and other drug delivery systems.

Hyaluronic acid-oleylamine and chitosan-oleic acid conjugate-based hybrid nanoparticle delivery via. dissolving microneedles for enhanced treatment efficacy in localized breast cancer.

Microneedle technology offers a minimally invasive treatment strategy to deliver chemotherapeutics to localized tumors. Amalgamating the surface functionalized nanoparticles with microneedle technology can potentially deliver drugs directly to tumors and subsequently target cancer cells via, overexpressed receptors on the cell surface, thereby enhancing the treatment efficacy while reducing side effects. Here, we report cetuximab anchored hyaluronic acid-oleylamine and chitosan-oleic acid-based hybrid nanoparticle (HA-OA/CS-OA NPT)-loaded dissolving microneedles (MN) for targeted delivery of cabazitaxel (CBT) in localized breast cancer tumor. The HA-OA/CS-OA NPT was characterized for their size, surface charge, morphology, physicochemical characteristics, drug release behavior, and in vitro anti-cancer efficacy. The HA-OA/CS-OA NPT were of ~125 nm size, showed enhanced cytotoxicity and cellular uptake, and elicited a superior apoptotic response against MDA-MB-231 cells. Subsequently, the morphology and physicochemical characteristics of HA-OA/CS-OA NPT-loaded MN were also evaluated. The fabricated microneedles were of ~550 µm height and showed loading of nanoparticles equivalent to ~250 µg of CBT. The ex vivo skin permeation study revealed fast dissolution of microneedles upon hydration, while the drug permeation across the skin exhibited ~4-fold improvement in comparison to free drug-loaded MN. In vivo studies performed on DMBA-induced breast cancer in female SD rats showed a marked reduction in tumor volume after administration of drug and nanoparticle-loaded microneedles in comparison to intravenous administration of free drug. However, the HA-OA/CS-OA NPT-MN showed the highest tumor reduction and survival rate, with the lowest body weight reduction in comparison to other treatment groups, indicating its superior efficacy and low systemic toxicity. Overall, the dissolving microneedle-mediated delivery of targeted nanoparticles loaded with chemotherapeutics offers a superior alternative to conventional intravenous chemotherapy.

Lipid-coated nanocrystals of paclitaxel as dry powder for inhalation: Characterization, in-vitro performance, and pharmacokinetic assessment.

BACKGROUND: Nanocrystals can be produced as a dry powder for inhalation (DPIs) to deliver high doses of drug to the lungs, owing to their high payload and stability to the shear stress of aerosolization force. Furthermore, lipid-coated nanocrystals can be formulated to improve the drug accumulation and retention in lung. OBJECTIVE: The present work involved the fabrication of paclitaxel nanocrystals using hydrophilic marine biopolymer fucoidan as a stabilizer. Thereafter, fabricated nanocrystals (FPNC) were surface-modified with phospholipid to give lipid-coated nanocrystals (Lipo-NCs). METHODS: The nanocrystals were fabricated by antisolvent crystallization followed by the probe sonication. The lipid coating was achieved by thin film hydration followed ultrasonic dispersion technique. Prepared nanocrystals were lyophilized to obtain a dry powder of FPNC and Lipo-NCs, used later for physicochemical, microscopic, and spectroscopic characterization to confirm the successful formation of desired nanocrystals. In-vitro and in-vivo investigations were also conducted to determine the role of nanocrystal powder in pulmonary drug delivery. RESULTS: Lipo-NCs exhibited slower drug release, excellent flow properties, good aerosolization performance, higher drug distribution, and prolonged retention in the lungs compared to FPNC and pure PTX. CONCLUSION: Lipid-coated nanocrystals can be a novel formulation for the maximum localization of drugs in the lungs, thereby enhancing therapeutic effects and avoiding systemic side effects in lung cancer therapy.

Biopolymer-based tumor microenvironment-responsive nanomedicine for targeted cancer therapy.

Nanomedicine has opened up new avenues for cancer treatment by enhancing drug solubility, permeability and targeted delivery to cancer cells. Despite its numerous advantages over conventional therapies, nanomedicine may exhibit off-target drug distribution, harming nontarget regions. The increased permeation and retention effect of nanomedicine in tumor sites also has its limitations, as abnormal tumor vasculature, dense stroma structure and altered tumor microenvironment (TME) may result in limited intratumor distribution and therapeutic failure. However, TME-responsive nanomedicine has exhibited immense potential for efficient, safe and precise delivery of therapeutics utilizing stimuli specific to the TME. This review discusses the mechanistic aspects of various TME-responsive biopolymers and their application in developing various types of TME-responsive nanomedicine.

Fabrication of gelatin coated polycaprolactone nanofiber scaffolds co-loaded with luliconazole and naringenin for treatment of Candida infected diabetic wounds.

The current study focuses on the development of gelatin-coated polycaprolactone (PCL) nanofibers co-loaded with luliconazole and naringenin for accelerated healing of infected diabetic wounds. Inherently, PCL nanofibers have excellent biocompatibility and biodegradation profiles but lack bioadhesion characteristics, which limits their use as dressing materials. So, coating them with a biocompatible and hydrophilic material like gelatin can improve bioadhesion. The preparation of nanofibers was done with the electrospinning technique. The solid state characterization and in-vitro performance assessment of nanofibers indicate the formation of uniformly interconnected nanofibers of 200-400 nm in diameter with smooth surface topography, excellent drug entrapment, and a surface pH of 5.6-6.8. The antifungal study showed that the nanofiber matrix exhibits excellent biofilm inhibition activity against several strains of Candida. Further, in-vivo assessment of nanofiber performance on C. albicans infected wounds in diabetic rats indicated accelerated wound healing efficacy in comparison to gauge-treated groups. Additionally, a higher blood flow and rapid re-epithelialization of wound tissue in the treatment group corroborated with the results obtained in the wound closure study. Overall, the developed dual-drug-loaded electrospun nanofiber mats have good compatibility, surface properties, and excellent wound healing potential, which can provide an extra edge in the management of complex diabetic wounds.

Advancements in microneedle fabrication techniques: artificial intelligence assisted 3D-printing technology.

Microneedles (MNs) are micron-scale needles that are a painless alternative to injections for delivering drugs through the skin. MNs find applications as biosensing devices and could serve as real-time diagnosis tools. There have been numerous fabrication techniques employed for producing quality MN-based systems, prominent among them is the three-dimensional (3D) printing. 3D printing enables the production of quality MNs of tuneable characteristics using a variety of materials. Further, the possible integration of artificial intelligence (AI) tools such as machine learning (ML) and deep learning (DL) with 3D printing makes it an indispensable tool for fabricating microneedles. Provided that these AI tools can be trained and act with minimal human intervention to control the quality of products produced, there is also a possibility of mass production of MNs using these tools in the future. This work reviews the specific role of AI in the 3D printing of MN-based devices discussing the use of AI in predicting drug release patterns, its role as a quality control tool, and in predicting the biomarker levels. Additionally, the autonomous 3D printing of microneedles using an integrated system of the internet of things (IoT) and machine learning (ML) is discussed in brief. Different categories of machine learning including supervised learning, semi-supervised learning, unsupervised learning, and reinforced learning have been discussed in brief. Lastly, a brief section is dedicated to the biosensing applications of MN-based devices.

Formulation and characterization of polyvinyl alcohol/chitosan composite nanofiber co-loaded with silver nanoparticle & luliconazole encapsulated poly lactic-co-glycolic acid nanoparticle for treatment of diabetic foot ulcer.

Chronic wounds are prone to fungal infections, possess a significant challenge, and result in substantial mortality. Diabetic wounds infected with Candida strains are extremely common. It can create biofilm at the wound site, which can lead to antibiotic resistance. As a result, developing innovative dressing materials that combat fungal infections while also providing wound healing is a viable strategy to treat infected wounds and address the issue of antibiotic resistance. Present work proposed anti-infective dressing material for the treatment of fungal strains Candida-infected diabetic foot ulcer (DFU). The nanofiber was fabricated using polyvinyl Alcohol/chitosan as hydrogel base and co-loaded with silver nanoparticles (AgNP) and luliconazole-nanoparticles (LZNP) nanoparticles, prepared using PLGA. Fabricated nanofibers had pH close to target area and exhibited hydrophilic surface suitable for adhesion to wound area. The nanofibers showed strong antifungal and antibiofilm properties against different strains of Candida; mainly C. albicans, C. auris, C. krusei, C. parapsilosis and C. tropicalis. Nanofibers exhibited excellent water retention potential and water vapour transmission rate. The nanofibers had sufficient payload capacity towards AgNP and LZNP, and provided controlled release of payload, which was also confirmed by in-vivo imaging. In-vitro studies confirmed the biocompatibility and enhanced proliferation of Human keratinocytes cells (HaCaT). In-vivo studies showed accelerated wound closure by providing ant-infective action, supporting cellular proliferation and improving blood flow, all collectively contributing in expedited wound healing.

Fabrication of dual drug-loaded polycaprolactone-gelatin composite nanofibers for full thickness diabetic wound healing.

Aim: Design of moxifloxacin and ornidazole co-loaded polycaprolactone and gelatin nanofiber dressing for diabetic wounds. Materials & methods: The composite nanofibers were prepared using electrospinning technique and characterized for in vitro drug release, antibacterial activity, laser doppler and in vivo wound healing. Results: The optimized nanofiber demonstrated an interconnected bead free nanofiber with average diameter <200 nm. The in vitro drug release & antimicrobial studies revealed that optimized nanofiber provided drug release for >120 h, thereby inhibiting growth of Escherichia coli and Stapyhlococcus aureus. An in vivo wound closure study on diabetic rats found that optimized nanofiber group had a significantly higher wound closure rate than marketed formulation. Conclusion: The nanofiber provided prolonged drug release and accelerated wound healing, making it a promising candidate for diabetic wound care.

This article is about making a wound dressing material of tiny fibres that have antibiotic properties to kill microbes at the wound site and make wounds heal faster. This is particularly important for people with diabetes, whose wounds often take longer to heal. The designed nanofibrous dressing releases antibiotic drugs at the wound site for more than 120 h, killing harmful microbes and thus avoiding their invasion at wound site. Also, animal experiments showed that the nanofibers shorten the time wounds take to heal by providing a suitable surface and a favourable environment for wound healing. The study concludes that the fabricated nanofiber dressing helps complex wounds heal faster, and could be a strong new dressing material for diabetic wound care.

Development and Evaluation of Amorphous Solid Dispersion of Riluzole with PBPK Model to Simulate the Pharmacokinetic Profile.

In the current work, screening of polymers viz. polyacrylic acid (PAA), polyvinyl pyrrolidone vinyl acetate (PVP VA), and hydroxypropyl methyl cellulose acetate succinate (HPMC AS) based on drug-polymer interaction and wetting property was done for the production of a stable amorphous solid dispersion (ASD) of a poorly water-soluble drug Riluzole (RLZ). PAA showed maximum interaction and wetting property hence, was selected for further studies. Solid state characterization studies confirmed the formation of ASD with PAA. Saturation solubility, dissolution profile, and in vivo pharmacokinetic data of the ASD formulation were generated in rats against its marketed tablet Rilutor. The RLZ:PAA ASD showed exponential enhancement in the dissolution of RLZ. Predicted and observed pharmacokinetic data in rats showed enhanced area under curve (AUC) and Cmax in plasma and brain with respect to Rilutor. Furthermore, a physiologically based pharmacokinetic (PBPK) model of rats for Rilutor and RLZ ASD was developed and then extrapolated to humans where physiological parameters were changed along with a biochemical parameter. The partition coefficient was kept similar in both species. The model was used to predict different exposure scenarios, and the simulated data was compared with observed data points. The PBPK model simulated Cmax and AUC was within two times the experimental data for plasma and brain. The Cmax and AUC in the brain increased with ASD compared to Rilutor for humans showing its potential in improving its biopharmaceutical performance and hence enhanced therapeutic efficacy. The model can predict the RLZ concentration in multiple compartments including plasma and liver.

Treatment of H. pylori infection and gastric ulcer: Need for novel Pharmaceutical formulation.

Peptic ulcer disease (PUD) is one of the most prevalent gastro intestinal disorder which often leads to painful sores in the stomach lining and intestinal bleeding. Untreated Helicobacter pylori (H. pylori) infection is one of the major reasons for chronic PUD which, if left untreated, may also result in gastric cancer. Treatment of H. pylori is always a challenge to the treating doctor because of the poor bioavailability of the drug at the inner layers of gastric mucosa where the bacteria resides. This results in ineffective therapy and antibiotic resistance. Current treatment regimens available for gastric ulcer and H. pylori infection uses a combination of multiple antimicrobial agents, proton pump inhibitors (PPIs), H2-receptor antagonists, dual therapy, triple therapy, quadruple therapy and sequential therapy. This polypharmacy approach leads to patient noncompliance during long term therapy. Management of H. pylori induced gastric ulcer is a burning issue that necessitates alternative treatment options. Novel formulation strategies such as extended-release gastro retentive drug delivery systems (GRDDS) and nanoformulations have the potential to overcome the current bioavailability challenges. This review discusses the current status of H. pylori treatment, their limitations and the formulation strategies to overcome these shortcomings. Authors propose here an innovative strategy to improve the H. pylori eradication efficiency.

Myricetin encapsulated chitosan nanoformulation for management of type 2 diabetes: Preparation, optimization, characterization and in vivo activity.

Type 2 diabetes mellitus (T2DM) is a serious and alarming disease attracting widespread attention. It is not a single metabolic disease; over time, it leads to serious disorders, namely, diabetic nephropathy, neuropathy, retinopathy and several cardiovascular, hepatocellular complications. The increase in T2DM cases in recent times has attracted significant attention. Currently, the medications available have side effects, and injectables are painful, causing trauma to the patients. Therefore, it is imperative to come up with oral delivery. In this background we report here a nanoformulation carrying natural small molecule Myricetin (MYR) encapsulated within Chitosan nanoparticles (CHT-NPs). MYR-CHT-NPs were prepared by ionic gelation method and evaluated using different characterization techniques. The in vitro release of MYR from CHT NPs in different physiological media showed pH dependence. in vivo pharmacodynamic study followed by oral administration in Albino Wistar rats showed better glycaemic control than existing drug. Further, the optimized nanoparticles also exhibited controlled increase in weight as compared to Metformin. The biochemistry profile of rats treated with nanoformulation reduced the levels of several pathological biomarkers, indicating additional benefits of MYR. Histopathological images exhibited no toxicity or changes in the major organs section in contrast to normal control, suggesting safe oral administration of the encapsulated MYR. Thus, we conclude that MYR-CHT-NPs represent an attractive delivery vehicle in improving the blood glucose level with controlled weight and have the potential to be safely administered orally for the management of T2DM.

Advances in lipid-based pulmonary nanomedicine for the management of inflammatory lung disorders.

Inflammatory lung disorders have become one of the fastest growing global healthcare concerns, with more than 500 million annual cases of disorders such as chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Owing to environmental changes and socioeconomic disparity, the numbers are expected to grow even more in years to come. The therapeutic strategies and approved drugs currently employed in the management of inflammatory lung disorders show dose-dependent resistance and pharmacokinetic limitations. This review comprehensively discusses lipid-based pulmonary nanomedicine as a potential platform to overcome these barriers while ensuring site-specific drug delivery and minimal side effects in nontargeted tissues for the management of noninfectious inflammatory lung disorders.

A Review on Screening Models for Potential Therapeutic Candidates and Targets Against SARS-CoV-2.

Coronaviruses are a group of known RNA virus which primarily infect the respiratory tract, and also neurological, enteric, and hepatic systems. Endemic outbreaks of Middle East Coronavirus Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) have been observed in recent decades. A new strain named the SARS CoV-2(- COVID-19) virus has now spread across the globe. SARS-CoV-2 is highly communicable and has culminated in a massive pandemic of COVID-19. Currently, no successful treatment is available. Therefore, an urgent need is there for new screening models that can aid in identifying the drugs with potential activity against COVID-19. The current review aims to discuss various in-silico, in- -vitro and in-vivo screening methods that can potentially be used to expedite the discovery of new active therapeutic candidates and vaccines, drug targets, and repurposing the commercially available drugs against COVID-19 for the effective management of the infection and thereby controlling this pandemic. Further, the current status of drugs and vaccines under clinical investigation has been summarized.

Electrospun nanofiber-based drug delivery platform: advances in diabetic foot ulcer management.

INTRODUCTION: Electrospinning is a facile and viable method for the fabrication of nanofibers. Electrospun nanofiber has a great potential in providing local drug or therapeutic molecule delivery to the wound site. The versatile nature of this technique ensures a broad scope of material used in the fabrication of nanofibers. AREA COVERED: A brief introduction to diabetic foot ulcer (DFU) is covered with its pathogenesis, followed by the role of electrospun nanofibers in DFU. This review covers the evolution of the electrospinning technique over the past few years, various types of electrospun nanofibers reported for DFU or chronic diabetic wounds, the challenges associated with the preparation of nanofibers, and various methods to evaluate their efficacy and performance in diabetic wound healing. EXPERT OPINION: Electrospinning-based nanofibers provide a safe, effective, and multifunctional system for effective management of DFU.

Targeted drug nanocrystals for pulmonary delivery: a potential strategy for lung cancer therapy.

INTRODUCTION: Lung cancer and metastases are major concerns worldwide. Although systemic chemotherapy is the recommended treatment, it is associated with various disadvantages, including nonselective drug distribution and systemic toxicity. In contrast, the pulmonary route ensures the localized delivery of drugs to the lung. Still, the pulmonary route is prone to clearance, limited drug dissolution, and local toxicity to healthy lung cells. Drug nanocrystals provide a potential strategy to enhance the therapeutic efficacy and mitigate the limitations of pulmonary delivery. AREAS COVERED: The development and potential application of nanocrystals in pulmonary delivery, their role in overcoming associated barriers, and strategies for site-specific and stimuli-responsive pulmonary delivery are outlined. This review also traces different in-vitro pulmonary models for assessments of the performance of drug nanocrystals and nanocrystals loaded carriers in pulmonary delivery. EXPERT OPINION: Enhanced stability, high aerosolization performance, better particle size distribution, improved penetration, sustained release of the drug, and minimal excipients usage makes drug nanocrystal an ideal candidate for pulmonary delivery. Besides, drug nanocrystals may provide selective cellular internalization with minimum clearance and maximum deposition. Furthermore, surface modified nanocrystals and nanocrystals in nanocarriers can exhibit a more prolonged, and site-specific release of the drug to cancer cells in the lungs.

Assessing the viability of Soluplus® self-assembled nanocolloids for sustained delivery of highly hydrophobic lapatinib (anticancer agent): Optimisation and in-vitro characterisation.

Nanocolloids are considered ideal carriers for hydrophobic drugs owing to their core-shell structure. Lapatinib is a potential anti-cancer agent, but its clinical use is limited because of its poor aqueous solubility, thus requiring larger oral doses with the associated toxicity. Thus, in the present study, we fabricated self-assembled nanocolloidal polymeric micelles (LP-PMs) of Soluplus® and Pluronic® F127 by the thin-film hydration method and assessed their delivery potential of the hydrophobic anti-cancer drug lapatinib (LP) and optimised these nanocolloidal polymeric micelles using Quality-by-Design approach. Amorphisation of the drug and no typical incompatibility other than hydrogen bonding in the LP-PMs was confirmed by solid-state characterisation. The LP-PMs exhibited a uniform size of 92.9 ± 4.07 nm, with a 5.06 mV zeta potential and approximately 87% drug encapsulation. The critical micellar concentration (CMC) of Soluplus® decreased from 6.63 × 10-3 to 4.4 × 10-3 mg/mL by incorporating Pluronic® F127. Further, the sustained release of LP from the LP-PMs was confirmed by in-vitro release studies showing 36% and 60% of LP released from the LP-PMs within 48 h in release media of pH 7.4 and pH 5.0, respectively. These results support their capability of preferential release at acidic tumor environment. Their hemocompatibility evidenced by hemolysis below accepted limits and no platelet aggregation with resistance to instant dilution illustrated their admirable blood compatibility and suitability for intravenous administration. The encapsulation of LP inside micelles enhanced the cytotoxicity of LP against SKBr3 breast cancer cells. Further, the LP-PMs were found to be stable over six months when stored at 2-8 °C. These findings indicate the improved potential of nanocolloidal polymeric micelles as promising carriers for the preferential and sustained delivery of hydrophobic anticancer drugs such as lapatinib to tumours.

Locust bean gum and sodium alginate based interpenetrating polymeric network microbeads encapsulating Capecitabine: Improved pharmacokinetics, cytotoxicity &in vivo antitumor activity.

A combination of biopolymers sodium alginate and locust bean gum has been used to prepare an interpenetrating polymeric network of an anticancer drug Capecitabine by ionotropic gelation method. For the optimization 32 levels, a full factorial design was employed to examine the influence of independent factors, i.e. polymer ratio and cross-linker concentration on responses particle size and drug entrapment. The obtained optimized formulation was examined for solid-state characterization, swelling study, in vitro drug release, SRB study, oral toxicity study, in vivo pharmacokinetic and in vivo antitumor study. The results of all the studies performed were found suitable in extending the release of a short elimination half-life drug with improved bioavailability and suggesting it to be safe and effective for oral drug delivery in treating colon cancer.

Biomimetic PCL-gelatin based nanofibers loaded with ciprofloxacin hydrochloride and quercetin: A potential antibacterial and anti-oxidant dressing material for accelerated healing of a full thickness wound.

An open wound is highly susceptible to microbial infection leading to elevated level of inflammatory response. For prompt healing, a wound requires a biomimetic dressing material with ideal hydrophilicity and tensile strength, possessing antimicrobial and antioxidant property. Although PCL-based nanofibers have sufficient tensile strength and biocompatibility, it lacks in terms of optimum hydrophilicity and biodegradation. Therefore, we fabricated a PCL-gelatin based electrospun nanofibers, enriched with quercetin and ciprofloxacin hydrochloride (CH). The average diameter of developed nanofibers was 725.943 ±â€¯201.965 nm, and devoid of chemical interaction between two drugs and polymers. CH and quercetin exhibited biphasic in-vitro release in phosphate buffer (pH 7.4). The in-vitro antibacterial and antioxidant property of scaffolds were evaluated by film-diffusion against Staphylococcus aureus and DPPH assay, respectively. The addition of gelatin along with CH and quercetin enhanced the hydrophilicity (contact angle = 48.8 ±â€¯2.95°) and biodegradation rate of the nanofibers. In-vitro biocompatibility of scaffold was examined by hemocompatibility and fibroblast viability using MTT assay. The results confirm the direct application of scaffold in the wounded area. Further, complete closure of full-thickness wound within 16 days, and regulation of hydroxyproline, SOD and catalase level in granulation tissues following treatment with scaffold, confirmed its application for accelerated wound healing.

Gold nanoparticles for sustained antileukemia drug release: development, optimization and evaluation by quality-by-design approach.

AIM: To design, develop, optimize and evaluate sustained-release dasatinib-loaded gold nanoparticles (DSB-GNPs) to treat chronic myeloid leukemia (CML) by using quality by design. MATERIALS & METHODS: In this study, we performed risk assessment, optimization, in vitro characterizations, stability study, drug release studies, cytotoxicity study and in vivo pharmacokinetic evaluation. RESULTS: DSB-GNPs of desired size, entrapment, smooth, spherical, stable and sustained drug release for 48 h were achieved. DSB-GNPs exhibited significantly more percentage growth inhibition and enhanced systemic bioavailability compared with pure DSB. CONCLUSION: The in vitro and in vivo evaluation exhibited that the DSB-GNPs have a potential cytotoxic effect, systemic bioavailability and sustained release making them a promising system of DSB delivery in the treatment of chronic myeloid leukemia.

Ciprofloxacin HCl and quercetin functionalized electrospun nanofiber membrane: fabrication and its evaluation in full thickness wound healing.

Microbial infection and oxidative damage of the fibroblast often results in prolonged and incomplete wound healing. Therefore, there is an increasing demand for a scaffold being effective to prevent any possible infection and neutralize excessively released free radicals. Herein, we designed a PCL-based nanofiber loaded with ciprofloxacin hydrochloride (CHL) and quercetin. Developed nanofiber showed the formation of smooth and continuous nanofiber with 101.59 ± 29.18 nm average diameter and entrapping the drugs in amorphous form without any possible physico-chemical interaction between drugs and excipient. High entrapment efficiency (CHL: 92.04% and Que: 94.32%) and prolonged in-vitro release (for 7 days) demonstrated the capability of scaffold to suppress any probable infection and oxidative damage, which was further confirmed by in-vitro antibacterial and antioxidant activity. The biocompatibility of scaffold for direct application to wound site was evaluated through hemocompatibility and cytocompatibility assay. The wound healing efficacies of nanofiber were assessed using full thickness wound model in rats, which displayed accelerated wound healing with complete re-epithelialization and improved collagen deposition within 16 days. In-vivo wound healing finding was further corroborated by SOD, catalase, and hydroxyproline assay. The current study validates the application of ciprofloxacin HCl and quercetin functionalized nanofiber as a potential wound dressing material.