Fabrication of chitosan-gelatin films incorporated with thymol-loaded alginate microparticles for controlled drug delivery, antibacterial activity and wound healing: In-vitro and in-vivo studies

Abstract

Previously, studies have demonstrated the unique characteristics of chitosan-gelatin films as wound dressings applications. However, their application has been limited due to their inadequacy of antimicrobial and anti-inflammatory characteristics. To improve the intended multifunctional characteristics of chitosan-gelatin film, in this study, we designed a novel composite film with the capability of controlled and prolonged release of thymol as a natural antioxidant and antimicrobial drug. Here, thymol-loaded ALG MPs (Thymol-ALG MPs) were prepared by electrospraying method and incorporated into the chitosan-gelatin film. The composite wound dressings of Thymol-ALG MPs incorporated in chitosan-gelatin film (CS-GEL/Thymol-ALG MPs) were characterized by in vitro and in vivo evaluations. The Thymol-ALG MPs demonstrated spherical and uniform morphology, with high encapsulation efficiency (88.9 ± 1.1 %). The CS-GEL/Thymol-ALG MPs exhibited high antibacterial activity against both Gram-positive and Gram-negative bacteria and no cytotoxicity for the L929 fibroblast cells. The release trend of thymol from CS-GEL/Thymol-ALG MPs and Thymol-ALG MPs followed a pseudo-Fickian diffusion mechanism. This wound dressing effectively accelerates the wound healing process at rats' full-thickness skin excisions. Also, the histological analysis demonstrated that the CS-GEL/Thymol-ALG MPs could significantly enhance epithelialization, collagen deposition, and induce skin regeneration. The present antibacterial composite film has promising characteristics for wound dressings applications.

Keywords: Alginate; Antibacterial; Chitosan; Drug delivery; Gelatin; Wound dress.