Diabetes mellitus is most common disorder characterize by hyperglycemia. Chronic hyperglycemia may lead to over production of free radicals thereby results in oxidative stress which impaired healing of wounds. Ferulic acid (FA) has been shown to have antidiabetic and antioxidant properties. The aim of the present study was to develop Ferulic acid nanoparticles and to study its hypoglycemic and wound healing activities. Ferulic acid-poly(lactic-co-glycolic acid) (FA-PLGA) nanoparticles were prepared by nano precipitation method. The prepared FA-PLGA nanoparticles had an average size of 240 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed the prepared FA-PLGA nanoparticles were spherical in shape. Drug encapsulation assay showed that 88.49% FA was encapsulated in PLGA. Carbopol 980 was used to formulate FA-PLGA nanoparticles loaded hydrogel. FA-loaded polymeric nanoparticles dispersion (oral administration) and FA-loaded polymeric nanoparticles based hydrogel (topical administration) treated wounds were found to epithelize faster as compared with diabetic wound control group. The hydroxyproline content increased significantly when compared with diabetic wound control. Therefore, the results indicate that FA significantly promotes wound healing in diabetic rats.
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 reepithelialization 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.
Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded SoluplusV R micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes. Box-Behnken response surface methodology was employed to optimize the formulation prepared using co-solvent evaporation method. Physicochemical characterization confirmed the nanospherical nature of Quercetin loaded SoluplusV R micelles (Qu-SMs) with average particle size ranging from 85-108nm, encapsulation efficiency of 63-77%. Solid state characterization confirmed the encapsulation of Qu in the micelles without any incompatibilities. Moving forward, the results of in vitro study revealed prolonged and slow release of Qu from the developed formulations. The in vivo pharmacokinetic study revealed improved bioavailability by enveloping the drug in SMs. Moreover, the study performed to evaluate the efficiency in diabetes treatment revealed an enhanced anti-diabetic effect. Thus, Qu-SMs can serve as potential carriers aimed at improving the anti-diabetic property of Qu.
Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu’s liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity.
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