Effects of hydrophobic drug incorporation on cubosome–cell membrane model interactions

Abstract The impact of incorporating drug molecules into lipid carriers needs to be examined when investigating the interactions between carriers and cell membranes. In this work, we investigate the effects of loading of the drug hydrocortisone on the interactions of monoolein cubosomes with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine cell membrane models (liposomes). Through the examination of the cubic structure and membrane, we elucidate the influence of the drug loading on the interaction. While the incorporation of the hydrocortisone did not alter the duration and kinetics of the cubic-to-lamellar phase transition, membrane property analysis by using Laurdan fluorescence probes showed slower kinetics in the drug-loaded cubosomes. This implies that the rate of lipid exchange between carriers and cell membranes was suppressed in the presence of drug molecules. Such an implication is important to consider when designing cubosomes as drug-delivery carriers, as it can affect factors such as their in vivo performance and drug uptake.