Betulinic Acid-Loaded Oleogel as a Novel Pharmaceutical Formulation for Potential Cutaneous Applications: Development, Characterization, and Biosafety Profile.

Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due to its lipophilic nature and low bioavailability, topical delivery systems are necessary for its proper administration. Oleogels are efficient carriers for the incorporation of hydrophobic biomolecules; however, their use for the delivery of BA remains scarce. Therefore, this study was designed to develop, characterize, and evaluate a BA-containing oleogel (BA-O) regarding its cutaneous safety profile as a potential pharmaceutical formulation targeting dermatologic issues. The findings illustrated the efficient formulation of BA as oleogel, the product presenting the specific conditions of topical semi-solid formulations in terms of physico-chemical characteristics and high biocompatibility in vitro and in ovo, as BA-O lacked a cytotoxic effect in HaCaT and JB6 Cl 41-5a skin cells (cell viability percentages being > 70%) and was categorized as non-irritant in EpiDerm™ tissues (viability > 80%) and on the chorioallantoic membrane (Irritation Score = 0.186). These results present the preclinical biosafety profile of BA-O with prospective potential for cutaneous applications that should be investigated in future studies.