Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
Nanomedicine (Lond). 2011 Sep;6(7):1245-55. doi: 10.2217/nnm.11.91.
Thermosensitive polymers are characterized by temperature-dependent aqueous solution properties. Below their lower critical solution temperature they are in an expanded state and fully dissolved, while above it they are dehydrated and insoluble. This has been exploited for the development of polymeric micelles that can be formed or destabilized depending on the solution temperature. Many micelle forming thermosensitive polymers have been described in literature, among which poly(N-isopropylacrylamide) (pNIPAAm), Pluronics (triblock copolymers of polypropylene oxide middle block flanked by two polyethylene oxide blocks) and poly(hydroxypropyl methacrylamide-lactate) (p(HPMAm-Lac(n))) are the most frequently studied and some drug-loaded formulations based on thermosensitive polymers have reached clinical trials. The first generation of micelles composed of thermosensitive polymers was based on mere hydrophobic interactions between polymer blocks, while more recently shell or core crosslinking was introduced, in order to improve their stability in the circulation after intravenous administration and therefore, the accumulation of their depot in diseased areas. Various formulations of drug-loaded micelles based on thermosensitive polymers have shown promising results in vitro, as well as in vivo. This review gives an overview of the most important recent developments regarding the design and synthesis of various types of thermosensitve polymers for drug delivery.
温敏聚合物的特点是其水溶液的性质随温度而变化。在其低临界溶液温度以下，它们处于扩张状态并完全溶解，而在其之上则脱水且不溶。这一特性已被用于开发聚合物胶束，其可以根据溶液温度形成或失稳。文献中已经描述了许多形成胶束的温敏聚合物，其中包括聚（N-异丙基丙烯酰胺）（pNIPAAm）、泊洛沙姆（聚环氧丙烷中间块两侧为两个聚环氧乙烷块的三嵌段共聚物）和聚（羟丙基甲基丙烯酰胺-乳酸）（p（HPMAm-Lac（n）））是研究最多的聚合物，并且一些基于温敏聚合物的载药制剂已经进入临床试验。第一代由温敏聚合物组成的胶束仅仅基于聚合物链段之间的疏水相互作用，而最近则引入了壳或核交联，以提高其在静脉给药后循环中的稳定性，从而增加其在病变部位的蓄积。基于温敏聚合物的载药胶束的各种制剂在体外和体内都显示出了有前景的结果。本综述概述了设计和合成各种类型温敏聚合物用于药物输送的最新进展。
