Temperature-responsive and Biodegradable Polymeric Micelles as drug carrier

定点给药已明显集中在提高药理学疗效和减少副作用。该聚合物胶束具有较低的临界胶束浓度，在水介质中具有很高的稳定性。在这个项目中，我们尝试使用温度响应性聚合物胶束制造位点特异性药物载体。即以n -异丙基丙烯酰胺(IPAAm)-D、l -丙交酯（dla）嵌段共聚物为原料制备了新型聚合物胶束。PIPAAm是一种具有较低临界溶解温度（LCST, 32‰）的热敏聚合物。在LCST以下，PIPAAm表现出亲水性，由于水化作用强，在水介质中可溶，在LCST以上由于脱水而不溶。这种相变发生在很窄的温度范围内。此外，聚（D， l-丙交酯）是一种众所周知的可生物降解聚合物。相应的嵌段共聚物在LCST下方形成了核(PDLLA)-壳（PIPAAm）的胶束结构。另一方面，在LCST上方的聚合物胶束形成聚集。这种现象是完全可逆的。在温度调制的控制下，可诱导选择性积累。也就是说，在一个物体中，热响应性聚合物胶束会聚集在局部受热的地方。这一发现无疑有助于特定部位给药。

Site-specific drug delivery has been markedly focused on the enhancement of pharmacological efficacy and reduction of side effects. The polymeric micelle shows very high stability in aqueous media due to its low critical micelle concentration. In this project, we attemped to fabricate sitespecific drug carriers using temperature-responsive polymeric micelle. Namely, novel type of polymeric micelle were prepared from N-isopropylacrylamide (IPAAm)-D,L-lactide(DLLA) block copolymer. PIPAAm is known to be a thermo-responsive polymer which has lower critical solution temperature (LCST, 32ﾟC). Below the LCST, PIPAAm shows the hydrophilicity and is soluble in aqueous media due to strong hydration and it is insoluble due to dehydration above the LCST.This phase transition takes place in narrow temperature range. Moreover, poly(D,L-lactide) is well-known as a biodegradable polymer. The corresponding block copolymer formed the micellar structure with core (PDLLA)-shell (PIPAAm) below LCST.On ther other hand, abovel LCST the polymeric micelles fomed aggregation. This phenomena was completely reversible. It was expected to induce selective accumulation controlled by temperature modulation. Namely, in a body, the thermo-responsive polymeric micelle would accumulate at the locally heated place. This finding surely contributes to site-specific drug delivery.