Tricaprin as a membrane permeability regulator: sustained small hydrophilic substance release from liposomes

Purpose Incorporating fatty acids into the phospholipid bilayer affects membrane packing order and permeability. We recently demonstrated that incorporating triglyceride into liposomes may alter membrane packing order and hydrophobic drug encapsulation capacity. This work investigated the effect of the saturated fatty acid-based triglyceride incorporation into liposomes carrying hydrophilic drugs. Methods Effects of tricaprin (TC) incorporation on the physicochemical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes encapsulated with small or large hydrophilic model drugs were investigated in terms of dithionite permeability, phase transition temperature, drug encapsulation efficiency, drug release rate, storage stability and cellular uptake of liposomes. Results TC incorporation into liposomes decreased dithionite permeability and raised phase transition temperatures of DMPC, indicating TC reduced membrane permeability. TC-induced thermogram changes in small hydrophilic drug model fluorescein-5-(and-6)-sulfonic acid (5-FSA)-encapsulated liposomes were comparable to those in drug-free/TC-incorporated liposomes. In contrast, they were significantly altered in large hydrophilic drug model FITC-BSA-encapsulated liposomes, suggesting macromolecule-induced membrane rearrangement. TC decreased the release rate of 5-FSA but increased that of FITC-BSA. Further, TC improved 5-FSA-encapsulated liposomes’ storage and freeze-drying stability. TC incorporation did not affect the cellular uptake of 5-FSA encapsulated in liposomes. Conclusion Our work demonstrates that saturated fatty acid-based triglyceride incorporation provides multiple benefits for liposomes carrying small, but not large, hydrophilic drugs by improving membrane properties.