Department of Clinical Biochemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel.
J Control Release. 2012 Jun 10;160(2):306-14. doi: 10.1016/j.jconrel.2011.12.022. Epub 2011 Dec 29.
Stable nano-sized vesicles with a monolayer encapsulating membrane were prepared from novel bolaamphiphiles with choline ester head groups. The head groups were covalently bound to the alkyl chain of the bolaamphiphiles either via the nitrogen atom of the choline moiety, or via the choline ester's methyl group. Both types of bolaamphiphiles competed with acetylthiocholine for binding to acetylcholine esterase (AChE), yet, only the choline ester head groups bound to the alkyl chain via the nitrogen atom of the choline moiety were hydrolyzed by the enzyme. Likewise, only vesicles composed of bolaamphiphiles with head groups that were hydrolyzed by AChE released their encapsulated material upon exposure to the enzyme. Injection of carboxyfluorescein (CF)-loaded vesicles with cleavable choline ester head groups into mice resulted in the accumulation of CF in tissues that express high AChE activity, including the brain. By comparison, when vesicles with choline ester head groups that are not hydrolyzed by AChE were injected into mice, there was no accumulation of CF in tissues that highly express the enzyme. These results imply that bolaamphiphilic vesicles with surface groups that are substrates to enzymes which are highly expressed in target organs may potentially be used as a drug delivery system with controlled site-directed drug release.
新型胆堿酯基两亲分子可以制备出具有单层囊泡膜的稳定纳米囊泡。头基通过氮原子或胆堿酯的甲基与两亲分子的烷基链共价键合。这两种两亲分子都与乙酰膽堿竞争结合乙酰膽堿酯酶（AChE），但只有通过氮原子与烷基链键合的胆堿酯基头基被酶水解。同样，只有由 AChE 水解的头基组成的囊泡在暴露于酶时才会释放其包封的物质。将具有可裂解胆堿酯基头基的 CF 负载囊泡注入小鼠体内，导致 CF 在表达高 AChE 活性的组织中积累，包括大脑。相比之下，当将不被 AChE 水解的胆堿酯基头基囊泡注入小鼠体内时，在高度表达该酶的组织中没有 CF 积累。这些结果表明，表面基团为靶器官中高度表达的酶的底物的两亲性囊泡可能被用作具有控制的靶向药物释放的药物传递系统。
