Bio-friendly oleic acid-based ufasomal topical gel of rosuvastatin for diabetic wound healing: In-vitro, ex-Vivo, and in-Vivo evaluation

Abstract

This study aimed to develop bio-friendly and biodegradable oleic acid-based ufasomes coated with chitosan for topical delivery of rosuvastatin for diabetic wound healing. Rosuvastatin was chosen as a suitable candidate due to its wound healing properties. Thin film hydration technique was implemented for the preparation of ufasomes at various concentrations of oleic acid. The most promising formulation (UF 5) was coated with chitosan. The effect of oleic acid and chitosan concentrations on vesicle Size, zeta-potential, polydispersity index, entrapment efficiency, and in-vitro drug release study was assessed. Optimum chitosan-coated ufasomal dispersion (CUF 3) was subjected to further characterizations, such as FT-IR, TEM, in-vitro release, broth microdilution susceptibility test, the effect of storage, ex-vivo skin permeability study, and wound healing efficiency in rats. Finally, CUF 3 was incorporated into chitosan gel base and examined for wound healing efficiency in rats. Uncoated ufasomal dispersion (UF 5) possessed the smallest vesicle Size (149.6 nm), the highest entrapment efficiency (79.48 %), an optimum zeta-potential (−35.78 mv), with polydispersity index of 0.18. FT-IR of coated ufasomes (CUF 3) reflected the effective coating of chitosan on the surface of ufasomes which coincided with the TEM image. Similar release profiles of UF 5 and CUF 3 were observed after 4 h of dissolution due to chitosan coating surrounding ufasomes. The cumulative percent of drug permeated across rat skin after 24 h for CUF 3 dispersion, and CUF 3 in chitosan gel were 11.21 % and 10.48 %, respectively, in comparison to 2.97 % in case of control gel. This was confirmed from the results of flux and permeability coefficient. A maximum skin retention and a controlled release effect with a reduced risk of systemic absorption of rosuvastatin were attained by CUF 3 in chitosan gel. Rosuvastatin encapsulated in ufasomal vesicles augmented the antimicrobial activity against Gram-negative and Gram-positive bacteria. A remarkable wound healing of CUF 3 in chitosan gel was confirmed by morphological and histopathological studies. Oleic acid-based ufasomes coated with chitosan could be a promising bio-friendly carrier for rosuvastatin to obtain a triple effect formulation for diabetic wound healing.