Temperature-responsive and Biodegradable Polymeric Micelles as drug carrier

靶向给药的研究主要集中在提高药物疗效和减少副作用方面。聚合物胶束由于其低的临界胶束浓度而在水介质中显示出非常高的稳定性。本项目尝试利用温度响应型聚合物胶束制备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（DLLA）嵌段共聚物为原料，制备了新型聚合物胶束。已知PIPAAm是具有较低临界溶解温度（LCST，32 ℃）的热响应聚合物。在LCST以下，PIPAAm表现出亲水性，在水介质中由于强的水化作用而溶解，而在LCST以上由于脱水作用而不溶，这种相变发生在很窄的温度范围内。此外，聚（D，L-丙交酯）作为可生物降解的聚合物是众所周知的。在低于LCST时，聚合物形成了核（PDLLA）-壳（PIPAAm）的胶束结构，而在高于LCST时，聚合物形成了聚集体。这种现象是完全可逆的。预期诱导受温度调节控制的选择性积累。也就是说，在体内，温度响应性聚合物胶束将在局部加热的地方聚集。这一发现肯定有助于位点特异性药物递送。

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.