Chung J E, Yokoyama M, Yamato M, Aoyagi T, Sakurai Y, Okano T
Institute of Biomedical Engineering, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo, Japan.
J Control Release. 1999 Nov 1;62(1-2):115-27. doi: 10.1016/s0168-3659(99)00029-2.
To achieve a combination of spatial specificity in a passive manner with a stimuli-responsive targeting mechanism, a temperature-responsive polymeric micelle is prepared using block copolymers of (poly(N-isopropylacrylamide-b-butylmethacrylate) (PIPAAm-PBMA)). The micelle inner core formed by self-aggregates of PBMA segments successfully loaded with a drug (adriamycin), and the outer shell of PIPAAm chains played a role of stabilization and initiation of micellar thermo-response. Optimum conditions were investigated for the micelle formation and drug loading into the inner cores in a view of micellar stability and function as drug carriers. Outer shell hydrophilicity that prevents inner core interaction with biocomponents and other micelles can be suddenly switched to hydrophobic at a specific site by local temperature increase beyond the LCST (lower critical solution temperature) (32.5 degrees C). These micelles showed reversible structural changes allowing drug release upon heating/cooling thermal fluctuations through the LCST. Polymeric micelles incorporated with adriamycin showed a dramatic thermo-responsive on/off switching behavior for both drug release and in vitro cytotoxicity according to the temperature responsive structural changes of a micellar shell structure. The reversible and sensitive thermo-response of the micelle opens up opportunities to construct a novel drug delivery system in conjunction with localized hyperthermia.
为了以被动方式实现空间特异性与刺激响应靶向机制的结合，使用（聚（N-异丙基丙烯酰胺-b-甲基丙烯酸丁酯）（PIPAAm-PBMA））嵌段共聚物制备了温度响应性聚合物胶束。由PBMA链段自聚集形成的胶束内核成功负载了一种药物（阿霉素），而PIPAAm链的外壳起到了稳定和引发胶束热响应的作用。从胶束稳定性和作为药物载体的功能角度出发，研究了胶束形成和药物负载到内核中的最佳条件。通过局部温度升高超过最低临界溶液温度（LCST）（32.5℃），可使防止内核与生物成分及其他胶束相互作用的外壳亲水性在特定部位突然转变为疏水性。这些胶束表现出可逆的结构变化，允许在加热/冷却通过LCST的热波动时释放药物。根据胶束壳结构的温度响应结构变化，掺入阿霉素的聚合物胶束在药物释放和体外细胞毒性方面均表现出显著的热响应开/关切换行为。胶束的可逆和敏感热响应为结合局部热疗构建新型药物递送系统提供了机会。
