Effects of Drug Hydrophobicity on Liposomal Stability

A major obstacle in drug delivery is the inability to effectively deliver drugs to their intended biological target without deleterious side‐effects. Delivery vehicles such as liposomes can minimize toxic side‐effects by shielding the drug from reaction with unintended targets while in systemic circulation. Liposomes have the ability to accommodate both hydrophilic and hydrophobic drugs, either in the internal aqueous core or the lipid bilayer, respectively. In the present study, fluorescein and rhodamine have been used to model hydrophilic and hydrophobic drugs, respectively. We have compared the stabilities of liposomes encapsulating these fluorophores as a function of lipid content, time, and temperature. At 25 and 37 °C, liposomes containing distearoyl phosphatidylcholine as the major phospholipid component were found to be more stable over time than those containing dipalmitoyl phosphatidylcholine, regardless of the fluorophore encapsulated. Liposomes loaded with fluorescein were found to be more stable than those with rhodamine. Dipalmitoyl phosphatidylcholine liposomes that encapsulated rhodamine were the least stable. The results indicate that the physical properties of the drug cargo play a role in the stability, and hence drug delivery kinetics, of liposomal delivery systems, and desired drug release times can be achieved by adjusting/fine‐tuning the lipid compositions.