Hybrid Liposomes with Pyrrolidinium Surfactants for the Encapsulation of Hydrophilic Drugs: Physicochemical Characterization and Cellular Uptake

Abstract Pyrrolidinium amphiphiles bearing a hydroxyethyl fragment [MPS n (OH), where n = 12, 14, 16, 18] were used as a modifier for the preparation of cationic hybrid liposomes based on phosphatidylcholine and cholesterol. The composition of the nanocarriers was optimized by varying the surfactant alkyl chain length and the lipid/surfactant molar ratio. The hydrophilic dye rhodamine B (RhB) was encapsulated into the liposomes with an encapsulation efficiency of up to 79 ± 3%. Incorporation of the cationic surfactants into the lipid bilayer increased the ζpotential from –13 ± 1 to +48 ± 2 mV, while the hydrodynamic diameter remained in the range of 100–130 nm, ensuring colloidal stability of the system. As the surfactant concentration increased, the ζpotential of the hybrid liposomes increased, with the effect being less pronounced for the longer-chain homologues. RhBloaded liposomes modified with MPS n (OH) maintained stable physicochemical characteristics for over 8 months at 4°C. Encapsulation of RhB slowed its release compared to the free dye. Liposomes modified with MPS14(OH) exhibited high intracellular accumulation in both normal (Wi38) and cancer (T98G) cells, with predominant localization in cytoplasm.