Asiaticoside polymeric nanoparticles for effective diabetic wound healing through increased collagen biosynthesis: In-vitro and in-vivo evaluation

Asiaticoside (AST) is a naturally available phytoconstituent that enables effective wound healing mainly by promoting collagen biosynthesis. However, the physicochemical nature of AST such as high molecular weight (959.12 g/mol), poor water solubility and poor permeability limits its therapeutic effects. This study aims to develop Asiaticoside polymeric nanoparticles (AST PNP) embedded in a gelatin based biodegradable hydrogel (15 % w/v) for application in the wound cavity to enable sustained release of AST and enhance its therapeutic effects. The AST PNP were fabricated in the desired size range (168.4 nm; PDI (0.09)) and the morphology, rate of fluid uptake, rate of water loss, and water vapor transmission rate of AST PNP incorporated hydrogel were determined. AST PNP gel showed porous structural morphology and possessed ideal characteristics as a graft for wound healing. The drug release kinetics and cellular uptake of AST PNP were investigated wherein, AST PNP demonstrated sustained release profile upto 24 h in comparison to free AST (complete release within 6 h) and exhibited an enhanced intra-cellular uptake in fibroblasts within 3 h compared to the free drug. In-vitrocell culture studies also demonstrated significant proliferation and migration of fibroblasts in the presence of AST PNP. Additionally, AST PNP gel upon application to the wounds of diabetic rats depicted improved wound healing efficacy in terms of improved collagen biosynthesis, upregulated COL-1 protein level (∼1.85 fold vs free AST), and enhanced expression of α-SMA compared to control groups. Altogether, formulation of AST as polymeric nanoparticles in a gel based carrier offered significant improvement in the therapeutic properties of AST for the management of diabetic wounds.