Biodegradable block copolymers as injectable drug-delivery systems
Biodegradable block copolymers as injectable drug-delivery systems
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作者：
Jeong, B;Bae, YH;Kim, SW
对刺激表现出物理化学反应的聚合物被广泛探索作为潜在的药物输送系统(1-4)，迄今为止研究的刺激包括化学物质以及温度、pH 和电场的变化，N-异丙基丙烯酰胺 (5,6) 和聚环氧乙烷-聚环氧丙烷-聚环氧乙烷的均聚物或共聚物（称为 泊洛沙姆）(7) 是热敏聚合物的典型例子，但它们在药物输送中的使用存在问题，因为它们有毒且不可生物降解，迄今为止用于药物输送的可生物降解聚合物大多采用可注射微球或植入系统的形式，这需要使用有机溶剂的复杂制造过程(8)。此类系统的缺点是，当封装蛋白质药物时，使用有机溶剂会导致变性。此外，固体形式需要手术插入，这通常会导致组织刺激和损伤。在这里，我们报告了由聚环氧乙烷和聚L-乳酸块组成的热敏性、可生物降解的水凝胶的合成，这些共聚物的水溶液表现出温度依赖性可逆凝胶-溶胶转变，水凝胶可以负载生物活性物质。 分子在高温（约 45 摄氏度）的水相中形成溶胶。在这种形式中，聚合物是可注射的。在皮下注射并随后快速冷却至体温时，负载的共聚物形成凝胶，可以充当药物的缓释基质。
Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems(1-4), Stimuli studied to date include chemical substances and changes in temperature, pH and electric field, Homopolymers or copolymers of N-isopropylacrylamide(5,6) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers)(7) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and nonbiodegradable, Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents(8). Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage, Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid), Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions, The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 degrees C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.