【作者】 盛光佳；

【导师】 程树军；

【作者基本信息】 华东理工大学 ， 材料科学与工程， 2011， 硕士

【摘要】 本文采用收敛法合成一种4代树枝状聚酯大分子,研究了基于此树枝状聚酯大分子的树枝化聚乳酸的合成及其载药微球的制备。该树枝化聚乳酸是一种中间为亲水性的PEG链段,两端为各有16个疏水性的PLLA链段的哑铃型三嵌段树枝化共聚物；其合成过程为：将氨基封端的树枝状聚酯大分子接到线性窄分布端羧基用N-羟基琥珀酰亚胺(NHS)活化的聚乙二醇(PEG)分子两端,脱除表面缩酮基保护后,以此为引发剂引发丙交酯开环聚合得到目标产物。通过红外光谱仪(FT-IR)、核磁共振波谱仪(NMR)、凝胶渗透色谱仪(GPC)、差示扫描量热仪(DSC)、热重分析仪(TG)等分析方法表征了树枝状聚酯大分子和树枝化共聚物。研究表明这种用该种方法合成的树枝状聚酯大分子结构明确,产物纯净；共聚物的玻璃化转变温度、熔点和结晶度都下降,亲水性得到提高；共聚物的PLLA链段可通过单体/引发剂的比例来调节,产物的分子量高并且分子量分布窄,分子表面有大量的活性端羟基可供化学修饰。将该共聚物用乳化溶剂挥发法制备成微球,用扫描电镜(SEM)、激光粒度仪(LS)等分析方法表征微球的形貌和粒径大小和分布,结果表明微球外形规整光滑,表面无空隙；微球平均粒径在1.40-3.17μm范围内,得到的微球粒径分布较为均一。制得的替莫唑胺-树枝化PLLA微球载药量可以达到20.1%,有一定的缓释效果,体外缓释时间为48h。更多还原

【Abstract】 The synthesis of dendronized polylactide (PLLA) and preparation of its drug-loading microshpere which was based on the four-generation polyester dendrons synthesized by divergent method were investigated. The dendronized PLLA is a well-defined dumbbell-shaped tri-block copolymer, consisting of hydrophobic PLLA and hydrophilic linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PLLA arm lengths, which have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization of L-lactide (LA). The terminal dendronized polyhydric PEG was prepared by the conjugation of amine-terminated fourth-generation polyester dendrons with NHS-activated PEG followed by the deprotection of acetonide groups at the surface of the dendrons. The dendrons and productions were characterized by FT-IR, NMR, GPC, DSC and TG. It was discovered that the dendrons were well-defined and the PLLA arms can be readily controlled by the feed ratio of LA monomer to the hydroxyl groups in PEG macro-initiator. The copolymer’s glass transition temperature, melting point and crystallinity were declined. And the copolymer has high molecular weight with narrow molecular weight distributions and improved hydrophilicity with much terminal hydroxyl which could be chemical modificated. The copolymer microsphere was prepared by emulsion-solvent evaporation method, characterized by SEM and SL, which showed a range of 1.40μm to 3.17μm in mean diameter with narrow microsphere size distribution and regular smooth surface without gap. The drug loading efficiency of temozolomide-dendronized polylactide microsphere is 20.1%and the in vitro control release time is 48 hours.更多还原