3D nanocomposite alginate hydrogel loaded with pitavastatin nanovesicles as a functional wound dressing with controlled drug release; preparation, in-vitro and in-vivo evaluation

Abstract

Nanocomposite alginate hydrogel containing pitavastatin nanovesicles were prepared as a bioactive wound dressing. Nanovesicles were formed via thin-film hydration technique using different types of lipids and sodium deoxycholate as a surfactant. Nanovesicles were evaluated for entrapment efficiency, particle size, zeta potential, in-vitro drug release besides their morphological properties. Nanovesicles were optimized applying 41 × 22 mixed factorial design using Design-Expert® VR software. The optimum formulation, composed of 400 mg Lipoid S45 and 0.1%w/v sodium deoxycholate, showed the highest entrapment efficiency (87.1 ± 0.3%) and drug release up to 3 days. Nanocomposite hydrogel was fabricated by incorporating the selected nanovesicles into calcium alginate hydrogel. The nanocomposite hydrogel was evaluated for water absorption capacity and in-vitro release besides in-vivo studies on dogs. Results revealed that the nanocomposite hydrogel possessed the highest water uptake at 21 days and the drug release was sustained up to 7 days. In-vivo studies on surgically induced skin wounds proved the success of the nanocomposite alginate hydrogel in promoting wound healing and wound closure. Histopathological studies revealed the superiority of nanocomposite hydrogel over plain hydrogel and drug suspension regarding the fast and proper rejuvenation of damaged skin layers. In conclusion, nanocomposite alginate hydrogel loaded with pitavastatin provided a promising, safe line for wound healing purposes.