Alginate/pectin hydrogel film incorporating atorvastatin and Jacaranda mimosifolia leaf extract for wound healing: Preparation, characterization and in vivo evaluation.

Wound healing is an integrative biological process with overlapping phases including, inflammation, granulation, and tissue remodeling. A potent wound dressing should be multifunctional with anti-inflammatory, antioxidant and tissue regeneration activities. Hydrogel films comprised of natural polymers are one of the best matrices that can be used to co-encapsulate multiple active molecules. In this context, alginate/pectin (ALG//PEC) hydrogel incorporating atorvastatin (ATR) and Jacaranda mimosifolia (J. mimosifolia) leaf extract was synthesized via solvent casting ionotropic gelation technique. The dual-loaded hydrogel film was characterized in terms of its chemical composition, tensile strength, in vitro drug release, hemocompatibility, and in vivo wound healing efficiency. Fourier-transform infrared (FTIR) analysis showed that the drug and the herbal extract were successfully incorporated without any chemical interaction. In addition, both blank hydrogel film and ATR/J. mimosifolia hydrogel film exhibited tensile strength of about 20.24 ± 0.66 and 21.68 ± 1.18 MPa, respectively and strain values of 68.73 ± 2.32 and 61.3 ± 1.06 %, respectively, which were suitable for wound dressing application. Moreover, in vitro drug release study indicated initial burst release of both ATR and J. mimosifolia reaching 34.87 % and 30.24 %, respectively after 2 h, then they reached 91.1 % and 50.23 %, respectively after 24 h, with ATR released at a faster rate in comparison to the herbal extract. When the dual-loaded hydrogel film was incubated with red blood cells, it displayed hemolytic potential of about 1.665 ± 0.063 %, which was comparable to blank hydrogel film 1.76 ± 0.035 %, showing excellent hemocompatibility. More importantly, in vivo studies in a rat model revealed that dual-loaded hydrogel film exhibited a superior wound closure in comparison to sterile gauze and blank hydrogel film-treated groups with the least inflammation and the highest collagen deposition. Furthermore, immucohistological investigation of CD31 as an angiogenic marker showed that dual-loaded hydrogel film displayed the highest expression level in comparison to all other treated groups, conforming that this dual-loaded hydrogel film could serve as a potential wound dressing film with anti-inflammatory and angiogenesis effects.