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

• Published in: International journal of biological macromolecules 2022-12, Vol.223 (Pt A), p.567-582
• Main Authors: Ahmady, Azin Rashidy, Razmjooee, Kavoos, Saber-Samandari, Saeed, Toghraie, Davood
• Format: Article
• Language: English
• Subjects: Alginate; Alginates - pharmacology; Animals; Anti-Bacterial Agents - pharmacology; Antibacterial; Chitosan; Drug delivery; Gelatin; Gram-Negative Bacteria; Gram-Positive Bacteria; Rats; Thymol - pharmacology; Wound dress
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.10.249

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. [Display omitted]