A novel multifaceted approach for wound healing: Optimization and in vivo evaluation of spray dried tadalafil loaded pro-nanoliposomal powder

The topical delivery of nanotherapeutics at the injury site for skin regeneration has received increasing attention as a strategy for wound treatment. This study aimed to investigate the preparation of spray dried tadalafil loaded pro-nanoliposomes powder as a novel system to accelerate wound healing process. The optimization was carried out employing 3(2) factorial design based on phospholipid and cholesterol concentrations. The physicochemical characterizations, in vitro cellular assessment and in vivo performance were evaluated. The results obtained pointed out that phospholipid concentration presented a positive effect on the entrapment efficacy and particle size, while cholesterol hindered the entrapment efficacy yet presented a prominent influence on particle size. Moreover, the optimized formulation showed a sustained release, high zeta potential and uniform spherical particles indicating entrapment of tadalafil in its amorphous state as demonstrated by FTIR and XPRD results. Cell viability and in vitro scratch assay demonstrated no cytotoxicity on human fibroblast cell lines and the ability of the drug and optimized formulation to promote cell migration. In vivo wound healing studies revealed significantly higher wound closure rates for areas treated with optimized loaded-formulation (65.95 +/- 6.47%) compared to unloaded formulation (29.78 +/- 9.65%), free drug (38.87 +/- 11.44%) and sham group (10.22 +/- 5.11%). In the in vivo study, histopathological specimens supported the previous results with presentation of cascade of healing elements via the angiogenetic activity of tadalafil. These outcomes provide an insight of a novel and emerging therapeutic drug system for wound treatment in clinical practice.