Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate)
Thermo-responsive drug delivery from polymeric micelles constructed using block copolymers of poly(N-isopropylacrylamide) and poly(butylmethacrylate)
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DOI：
10.1016/s0168-3659(99)00029-2
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发表时间：
1999-11-01
影响因子：
10.8
通讯作者：
Okano, T
中科院分区：
文献类型：
--
作者：
Chung, JE;Yokoyama, M;Okano, T
为了实现被动方式的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聚合物胶束。成功装载药物（阿霉素）的PBMA片段的自聚集体形成胶束内核，PIPAAm链的外壳起到稳定和引发胶束热响应的作用。从胶束稳定性和药物载体功能的角度考察了胶束形成和载药的最佳条件。外壳亲水性可以阻止内核与生物组分和其他胶束的相互作用，当局部温度超过LCST（较低临界溶液温度）（32.5℃）时，外壳亲水性可以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，允许药物在加热/冷却通过LCST的热波动时释放。通过胶束壳结构的温度响应变化，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表现出显著的热响应性开关行为。胶束的可逆和敏感的热反应为构建一种结合局部热疗的新型药物输送系统提供了机会。(C) 1999 Elsevier Science B.V.版权所有
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. (C) 1999 Elsevier Science B.V. All rights reserved.