Application of micro-emulsion formulation in improving the antiproliferative performance of Salix mucronata (Thunb) leaves with chemical investigation of the active extract.

Abstract

This study aims to obtain micro-emulsion delivery system of safe cytotoxic drug from Salix mucronata Thunb, (Salicaceae). Dried powdered leaves were extracted with 70% ethanol (crude) and successively extracted using petroleum ether, chloroform and 80% ethanol. Acute toxicity proved its safety (LD50 = 2.583 g/kg). Moreover, mutagenicity tests revealed that there is no significant difference between treated and control groups. Antioxidant potential of crude extract evaluated by DPPH, ABTS, and FRAP assays, revealed 101.19, 114.74 and 100.97 mg, respectively, calculated as Trolox equivelant (TE/g). Successive extracts showed cytotoxic activity against liver (HEPG2) and breast (MCF7) carcinoma cell lines. Different extracts were incorporated in micro-emulsion formulations (MEF) and characterized for physicochemical and drug release properties. (MEFs) were reinvestigated for improvement in cytotoxic performance to reveal enhancement in all extracts. Most promising fraction was the polar one; ethanol extract with IC50 (18.2 μg/mL) against (HEPG2) dropped to (13.8 μg/mL) after formulation with better drug release action. Total phenolics and flavonoids contents were estimated as gallic acid and catechin equivalents, respectively. HPLC was performed to get insight on active fraction secondary metabolites that revealed 21 phenolic acids, catechol (16.07 mg/g) was the major and 16 flavonoids, hisperidin was the major (81.50 mg/g).