Rijcken C J F, Soga O, Hennink W E, van Nostrum C F
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
J Control Release. 2007 Jul 31;120(3):131-48. doi: 10.1016/j.jconrel.2007.03.023. Epub 2007 May 1.
Polymeric micelles and vesicles have emerged as versatile drug carriers during the past decades. Furthermore, stimuli-responsive systems are developed whose properties change after applying certain external triggers. Therefore, a triggered release of drugs from stimuli-sensitive micelles and vesicles has become an interesting challenge in the pharmaceutical field. Polymeric micelles or vesicles are mainly composed of amphiphilic block copolymers that are held together in water due to strong hydrophobic interactions between the insoluble hydrophobic blocks, thus forming a core-shell or bilayer morphology. Consequently, destabilisation of these assemblies is induced by increasing the polarity of the hydrophobic blocks. Preferably, this process should be the consequence of an external trigger, or take place in a certain time frame or at a specific location. A variety of mechanisms has recently been described to accomplish this transition, which will be reviewed in this paper. These mechanisms include the destabilisation of polymeric micelles and vesicles by temperature, pH, chemical or enzymatic hydrolysis of side chains, oxidation/reduction processes, and light.
在过去几十年中,聚合物胶束和囊泡已成为多功能药物载体。此外,还开发了刺激响应系统,其性质在施加某些外部触发因素后会发生变化。因此,从刺激敏感的胶束和囊泡中触发药物释放已成为制药领域一个有趣的挑战。聚合物胶束或囊泡主要由两亲性嵌段共聚物组成,由于不溶性疏水嵌段之间强烈的疏水相互作用,它们在水中聚集在一起,从而形成核壳或双层形态。因此,通过增加疏水嵌段的极性来诱导这些组装体的不稳定。优选地,这个过程应该是外部触发的结果,或者在特定的时间框架内或特定位置发生。最近已经描述了多种实现这种转变的机制,本文将对此进行综述。这些机制包括通过温度、pH值、侧链的化学或酶促水解、氧化/还原过程以及光来使聚合物胶束和囊泡不稳定。