Association Interactions of Hydroxychloroquine Sulfate With DMPG Liposomes: CTAB-Induced Lipid Solubilization and Subsequent Drug Release.

Herein, we investigated the molecular interactions of an antimalarial drug, hydroxychloroquine sulfate (HCQS), with liposome nanocarriers. Spectroscopic analyses revealed that in the presence of the anionic liposomes (DMPG), HCQS undergoes significant microenvironmental changes, including a marginal red shift in absorption, a 17 nm blue shift in emission, and a marked reduction in fluorescence lifetime, indicating a partial localization of the drug within the liposomal hydrophobic bilayer. Steady-state and time-resolved anisotropy measurements revealed the restricted probe mobility in liposomal environments. However, cholesterol-dependent studies indicated that increased membrane rigidity reduced the HCQS-liposome association interactions. Furthermore, solubilization of the anionic liposomes by a cationic surfactant, CTAB led to the complete release of the bound HCQS, with reversibility in spectral signatures. It is suggested that due to mixed micelle formation between CTAB and the lipid molecules, the drug gets released from the liposome environment. These findings highlight the interplay of electrostatic and hydrophobic forces in governing the HCQS-liposome association and provide valuable insights for rational design of liposome-based drug delivery systems.