Theoretical Assessment of Fluorinated Phospholipids in the Design of Liposomal Drug-Delivery Systems.

摘要: Fluorinated phospholipid analogues are investigated as potential substrates for phospholipase A2 (PLA2) using classical molecular dynamics simulations and quantum mechanics/density functional theory calculations. The fluorinated α-fluoro (HF-ProAEL) α,α-difluoro (F2-ProAEL) conjugates of (R)-1-O-hexadecyl-2-palmitoyl-sn-glycero-3-phoshocholineglycerol (ProAEL). Our results provide a theoretical assessment the usefulness these lipids in rational design liposomal drug-delivery systems. α-fluorine-substituted found to be secretory PLA2, with sufficient accessibility water active site allow enzymatic hydrolysis. Because inherently less stable nature HF-ProAEL F2-ProAEL when compared that ProAEL, hydrolytic reaction is predicted occur at progressively faster rate; more electronegative substituent α-position effectively lowers energy barrier We conclude partially facilitate vesicles mixtures desirable physicochemical properties still subjects important pharmaceutically proven mechanisms.