Development and optimization of transethosomal gel of apigenin for topical delivery: In-vitro, ex-vivo and cell line assessment

Abstract

The main aim of this study was to optimize the transethosomes of apigenin formulated by the thin film hydration method using surfactant Span 80. Response surface Box-Behnken design with three levels of three factors was used to design and optimize the formulations. The prepared transethosomal formulations were characterized for entrapment efficiency, vesicle size, and flux to obtain the optimized formulation batch. The optimized batch was further incorporated into the gel and characterized for the in-vitro, ex-vivo, and cytotoxic studies. The result showed the optimized transethosomes were smooth, nanosized, unilamellar, and spherical with an entrapment efficiency of 78.75 ± 3.14 %, a vesicle size of 108.75 ± 2.31 nm, and a flux of 4.10 ± 0.63 µg/cm²/h. In-vitro cumulative drug release of transethosomal gel of apigenin (TEL gel) and the conventional gel was 92.25 ± 3.5 % and 53.40 ± 3.10 %, respectively, after 24 h study. Ex-vivo permeation of TEL gel and conventional gel showed 86.20 ± 3.60 % and 51.20 ± 3.20 % permeation of apigenin at 24 h, respectively. A cytotoxic study confirmed that TEL gel significantly reduces cell viability compared to conventional gel. The results suggested that topical application of apigenin transethosomal gel may be a better treatment strategy for skin cancer because of the prolonged sustained release of the drug and the better permeability of apigenin through the skin.

Keywords: Apigenin; Box-Behnken design; Skin cancer; Topical delivery; Transethosome.