Preclinical Safety Evaluation of Dual Drug-Loaded Nanolipidic Carriers of Dissolvable Patches: In-Vitro and In-Vivo Safety Assessment.

The present research investigates the preclinical safety of a novel formulation (patent application number 202211045937, 5929IN008), comprising of tetrahydrocurcumin and folic acid coloaded nanostructured lipid carriers (THC-FA-NLCs) integrated into dissolvable patches (DP). The potential for skin irritation and acute dermal toxicity was assessed in rats as per the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404, and 410). Additionally, cytotoxicity testing was performed using human dermal fibroblast (HDF) cells. Primary skin irritation study post topical application of THC-FA-NLCs-DP and Blank-DP to intact skin sites in rats, after 72 h, showed no adverse reactions. Furthermore, a 28-day repeated dermal toxicity study, followed by biochemical and histopathological analyses, revealed minimal alterations and no significant skin lesions. In cytotoxicity assays, THC-FA-NLCs-DP demonstrated negligible cytotoxic effects in HDF cells, which were further confirmed through histopathological evaluation. The safety demonstrated by the developed formulation in preclinical studies supports its further clinical investigation. These studies support the potential of THC-FA-NLCs-DP as a viable alternative for treating chronic wounds, particularly diabetic foot ulcers.