两亲性三嵌段共聚物的合成、表征及其药控释放行为的研究

Synthesis,Characterization and Controlled Drug Release Behavior of Amphiphilic Triblock Copolymers

以三硫代碳酸双(α,α′-二甲基α-″-乙酸)酯为链转移剂,以苯乙烯(St)或甲基丙烯酸甲酯(MMA)为亲油性单体,以甲基丙烯酸二甲氨基乙酯(DMA)为亲水性单体,AIBN为引发剂,通过可逆加成断裂链转移(RAFT)聚合得到两种两亲性三嵌段共聚物,通过凝胶渗透色谱(GPC)测试其组成分别为PS16-PDMA56-PS16,PMMA11-PDMA38-PMMA11,PMMA15-PDMA40-PMMA15,Mw/Mn分别为1.20、1.27、1.29。并用1HNMR进一步表征了嵌段共聚物结构。TEM及粒度测试研究发现,PS-PDMA-PS在特定溶剂中可以自组装成球形胶束,其尺寸在380 nm左右;而PMMA-PDMA-PMMA自组装成的胶束则呈均匀的球形,胶束分散较好,粒径约在120 nm左右。并研究了3种胶束对水溶性模型药物对羟基苯甲醚(HOA)的缓释效果,发现在同一时间PS-PDMA-PS胶束的累积释放量比其他胶束的小,药物的控释遵循扩散机理,并且胶束尺寸对药物的释放速率影响较大。

Amphiphilic triblock copolymers were synthesized by RAFT technique ,using bis（ 2-carboxylpropan-2-yl） trithiocarbonate （ BCPTFC ） as the chain transfer agent, azodiisobutyronitrile （ AIBN ） as initiator, styrene （S） and methyl methacrylate （MMA） as hydrophobic monomers and N, N- dimethylaminoethyl methacrylate（DMA） as hydrophilic monomer. The copolymer were characterized by GPC, their segmental compositions were measured as PS16-PDMA56-PS16, PMMA11-PDMA38-PMMA11 and PMMA15-PDMA40-PMMA15, the polydistribution indexes of which are 1.20, 1.27 and 1.29 respectively. Structures of the block copolymers were confirmed by ^1HNMR. The serf-assembly behaviors of triblock copolymers were investigated by TEM and nanosizer. It was found that the micelle of PS-PDMA-PS has spherical shape, about 380 nm in diameter. The regular spherical shape for PMMA-PDMA-PMMA via their macromolecular aggregation were also observed, and the size of their mieelles is smaller, about 120 nm. p-Hydroxyanisole was used as a model drug for the study of the drug loading and controlled release behavior in distilled water. It was found that the amount of cumulative release in the micelles of PS-PDMA-PS is smaller than that in the micelles of PMMA-PDMA-PMMA at the same time. As a result, the drug could be released slowly from these particles via diffusion process,and the release rate is affected by the micellar size.