Toward overcoming the limitations of liposomes in targeted drug delivery, monolayer membrane vesicles with cationic head groups were developed. These vesicles were prepared from novel bolaamphiphiles with acetylcholine (Ach) head groups that allow vesicle disruption by enzymatic hydrolysis with acetylcholine esterase (AChE). After administration of vesicles encapsulated with carboxyfluorescein (CF) into mice pretreated with pyridostigmine (to inhibit peripheral AChE), a significant amount of encapsulated CF was accumulated in the brain. Injection of vesicles with encapsulated enkephalin (ENK) into mice produced analgesia, while injection of ENK in its free form did not cause any analgesic effect. The results demonstrate the potential of our novel vesicles for targeting water-soluble drugs and peptides to the brain.
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