Physicochemical characterization and in vitro biological evaluation of TPGS-stabilized cationic nanoliposomes for 8-bromo-6-chloroflavone delivery

Abstract

Flavonoids with halogen substituents represent a promising group of bioactive compounds, but their poor aqueous solubility and limited bioavailability restrict their therapeutic application. This study aimed to develop and evaluate a SPC/cholesterol/TPGS/DOTAP-modified cationic liposomal system for the delivery of 8-bromo-6-chloroflavone (BrCl-F), a halogenated flavone with previously demonstrated anticancer activity and ability to interact with lipid bilayers. BrCl-F-loaded liposomes were prepared using SPC, cholesterol, DOTAP and TPGS, and characterized in terms of particle size, polydispersity, zeta potential, morphology, encapsulation efficiency, storage stability, behavior in serum-containing media, interaction with human serum albumin, cytotoxic activity and hemolytic activity. The formulation formed nanosized vesicles with an initial hydrodynamic diameter of approximately 125 nm, low polydispersity and positive surface charge. BrCl-F was efficiently encapsulated, although a partial decrease in drug retention and moderate vesicle reorganization occurred during storage. In serum-containing media, liposomes underwent charge neutralization without extensive aggregation. Albumin fluorescence studies showed that encapsulation markedly reduced the direct interaction between BrCl-F and HSA compared with the free compound. Biologically, BrCl-F-Lipo enhanced activity against CLBL-1 cells, reduced toxicity toward non-cancerous MDCK cells, and showed low toxicity toward erythrocytes under the tested conditions. Together, these results highlight the relevance of TPGS/DOTAP-modified liposomes in shaping the stability, protein interactions and biological response of BrCl-F.