Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers
Thermo-responsive polymer nanoparticles with a core-shell micelle structure as site-specific drug carriers
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DOI：
10.1016/s0168-3659(97)00040-0
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发表时间：
1997-10-13
影响因子：
10.8
通讯作者：
Okano, T
中科院分区：
文献类型：
--
作者：
Cammas, S;Suzuki, K;Okano, T
大多数先进的药物递送策略的成功需要开发复杂的新的位点特异性载体。几种新的靶向方法使用物理和化学信号，如磁场或pH值或温度的变化作为靶向和触发工具。除了位点特异性之外，载体还应实现被动靶向以避开身体的网状内皮系统（RES），并表现出长的血液循环时间，以有效地将活性药物分布到作用位点（主动靶向）。为了满足这些要求，已经从由N-异丙基丙烯酰胺（IPAAm）（热响应外壳）和苯乙烯（St）（疏水内核）组成的两亲性嵌段共聚物制备了热响应聚合物胶束。用DMF溶液对水透析的方法形成了在水介质中非常稳定的聚合物胶束。胶束具有单峰尺寸分布（24+/-4nm），CMC为约10 mg/l。这些胶束具有小直径和低临界胶束浓度，提供了可能具有长血液循环时间和低RES摄取的载体。当温度升高到热响应嵌段链的转变温度（32摄氏度）以上时，外壳链膨胀并塌陷，允许胶束之间的聚集并有利于与细胞膜表面的结合相互作用。而且，这些变化是可逆的。疏水分子被证明是纳入内部的疏水核心的温度响应胶束。因此，这些胶束对于使用温度变化作为触发器的药物的位点特异性递送是有价值的。(C)1997年Elsevier Science B.V.
The success of most advanced drug delivery strategies requires development of sophisticated new site-specific carriers. Several new targeting methods use physical and chemical signals such as magnetic fields or changes in pH or temperature as targeting and triggering tools. In addition to site-specificity, the carrier should achieve passive targeting to evade the body's reticulo-endothelial system (RES) and exhibit long blood circulation times in order to efficiently distribute active drug to the site of action (active targeting). To fulfil these requirements, thermo-responsive polymeric micelles have been prepared from amphiphilic block copolymers composed of N-isopropylacrylamide (IPAAm) (a thermo-responsive outer shell) and styrene (St) (hydrophobic inner core). The polymeric micelle which is very stable in aqueous media was formed by the dialyzed method from DMF solution against water. The micelles have a unimodal size distribution (24+/-4 nm) and CMC was around 10 mg/l. These micelles have a small diameter with a low critical micelle concentration, providing a carrier that may have long blood circulation times and a low RES uptake. When the temperature is increased above the transition temperature of the thermo-responsive block chains (32 degrees C), the outer shell chains dehydrate and collapse, allowing aggregation between micelles and favoring binding interactions with cell membrane surfaces. Moreover, these changes are reversible. Hydrophobic molecules are shown to be incorporated into the inner hydrophobic core of the thermo-responsive micelles. Consequently, these micelles are Valuable for site-specific delivery of drugs using changes in temperature as a trigger. (C) 1997 Elsevier Science B.V.