Temperature-responsive and Biodegradable Polymeric Micelles as drug carrier

温度响应且可生物降解的聚合物胶束作为药物载体

• 批准号: 08672569
• 负责人: AOYAGI Takao
• 金额: $ 1.41万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672569/
• 关键词: Polymeric micelle; Biodegradable; Temperature-responsive; Poly (N-isopropylacrylamide); Poly (lactide); 薬物送達システム; ポリイソプロピルアクリルアミド; ポリ-D,L-ラクチド; ブロック共重合体; 温度応答性; 生分解性; ブロックコポリマー; ポリ乳酸

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.

靶向给药主要集中在提高药理作用和减少副作用上。由于其临界胶束浓度较低，聚合物胶束在水介质中表现出很高的稳定性。在本项目中，我们尝试利用温度响应性聚合物胶束来制备特定部位的药物载体。即由N-异丙基丙烯酰胺(IPAAM)-D，L-丙交酯(DLLA)嵌段共聚制备了新型聚合物胶束。PIPAAM是一种热敏性聚合物，具有较低的临界溶解温度(Lcst，32ﾟC)。在LcST以下，PIPAAm表现出亲水性，由于强烈的水合作用而溶于水介质，在LcST以上由于脱水而不溶，这种相变发生在较窄的温度范围。此外，聚(D，L-丙交酯)是众所周知的可生物降解的聚合物。相应的嵌段共聚物在LcST以下形成具有核(PDLLA)-壳的胶束结构(PIPAAm)，而在LcST以上形成聚合物胶束聚集。这种现象是完全可逆的。它有望诱导受温度调制控制的选择性积累。也就是说，在一个物体中，对温度敏感的聚合物胶束会聚集在局部加热的地方。这一发现肯定有助于特定部位的药物输送。

项目成果

J.E.Chung, M.Yokoyama, K.Suzuki, T.Aoyagi, Y.Sakurai, T.Okano: ""Reversibly thermo-resposive alkyl-terminated poly (N-isoprophlacrylamide) core-shell micellar structures"" Colloids and Surfaces, B : Biointerfaces. 9. 37-48 (1997)

J.E.Chung、M.Yokoyama、K.Suzuki、T.Aoyagi、Y.Sakurai、T.Okano：“可逆热响应烷基封端聚（N-异丙丙烯酰胺）核壳胶束结构”胶体和表面，B

F.Kohori, K.Sakai, T.Aoyagi, M.Yokoyama, Y.Sakurai, T.Okano: "Preparation and Characterization of Thermally Responsive Block Copolymer Micelles Comprising Poly(N-isopropylacrylamide-b-DL-lactide" Journal of Controlled Release. 55. 87-98 (1998)

F.Kohori、K.Sakai、T.Aoyagi、M.Yokoyama、Y.Sakurai、T.Okano：“包含聚（N-异丙基丙烯酰胺-b-DL-丙交酯的热响应嵌段共聚物胶束的制备和表征”）受控杂志

F.Kohori, K.Sakai, T.Aoyagi, M.Yokoyama, Y.Sakurai, T.Okano: ""Preparation and Characterization of Thermally Responsive Block Copolymer Micelles Comprising Poly (N-isopropylacrylamide-b-DL-lactide)"" Journal of Controlled Release. 55(1). 87-98 (1998)

F.Kohori、K.Sakai、T.Aoyagi、M.Yokoyama、Y.Sakurai、T.Okano：“包含聚（N-异丙基丙烯酰胺-b-DL-丙交酯）的热响应嵌段共聚物胶束的制备和表征”

J.E.Chung, M.Yokoyama, K.Suzuki, T.Aoyagi, Y.Sakurai, T.Okano,: "Reversibly thermo-resposive alkyl-terminated poly(N-isopropylacrylamide) core-shell micellar structures" Colloids and Surfaces, B : Biointerfaces. 9. 37-48 (1997)

J.E.Chung、M.Yokoyama、K.Suzuki、T.Aoyagi、Y.Sakurai、T.Okano，：“可逆热响应烷基封端聚（N-异丙基丙烯酰胺）核壳胶束结构”胶体和表面，B：

J.E.Chung,M.Yokoyama,K.Suzuki,T.Aoyagi,Y.Sakurai,T.Okano,: "Reversibly thermo-resposive alkyl-terminated poly(N-isopropylacrylamide) core-shell micellar structures" Colloids and Surfaces,B:Biointerfaces. 9. 37-48 (1997)

J.E.Chung，M.Yokoyama，K.Suzuki，T.Aoyagi，Y.Sakurai，T.Okano，：“可逆热响应烷基封端聚（N-异丙基丙烯酰胺）核壳胶束结构”胶体和表面，B：