Lipid nanoemulsion incorporating DOTAP reverse micelles as clinically translatable carriers of ALDH inhibitors for lung cancer therapy

Abstract

Lung cancer remains the most prevalent malignancy worldwide and the leading cause of cancer-related deaths. In this study, we designed and optimized a lipid nanosystem incorporating the cationic lipid DOTAP by utilizing reverse micelle structures to enhance pulmonary tropism. Fluorescence quenching assays confirmed the incorporation of reverse micelles into the oily core, thus validating the structural integrity of the system. This nanosystem was tailored for the encapsulation of ABD0171, a potent inhibitor of ALDH1A3, an enzyme strongly associated with chemoresistance in lung cancer. Physicochemical characterization revealed robust colloidal properties with a particle diameter of 60 nm, a surface charge of +45 mV, and a drug encapsulation yield of 99%. In vitro, formulations with/without DOTAP demonstrated high efficacy against epithelial-like H358 cells derived from human bronchioalveolar carcinoma, with IC50 values View larger version (29K): org.highwire.dtl.DTLVardef@dbc8org.highwire.dtl.DTLVardef@5d5187org.highwire.dtl.DTLVardef@9391f3org.highwire.dtl.DTLVardef@52fd54_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG