【作者】 鞠明杰；

【导师】 杲云；

【作者基本信息】 华东理工大学 ， 材料科学与工程， 2012， 博士

【摘要】 树枝状大分子聚酯是至今为止唯一可降解的树枝状大分子,具有良好的生物相容性,低的细胞毒性,在药物载体、靶向控制释放以及组织工程领域具有广泛的应用前景。本文以聚乙二醇为中心,采用发散法合成了1-4代末端含有不同数量羟基的树枝化聚乙二醇大分子引发剂,并研究了基于此大分子引发剂的树枝化聚合物的合成及性质。研究主要分为以下三个方面：(1)含有梳状聚己内酯(PCL)和线性聚乙二醇(PEG)的哑铃型三嵌段共聚物的合成与研究以上述含有羟基的1-4代树枝化聚乙二醇为大分子为引发剂,引发己内酯开环聚合,合成了一种中间为亲水性的PEG链段,两端为32个疏水性的PCL链段的哑铃型三嵌段共聚物。共聚物中PCL链段聚合度可通过单体/引发剂比例加以调节。这种支化结构聚酯材料不仅能达到很高分子量和很窄的分子量分布,同时具有较好的亲水性,以及大量的活性端羟基可用于化学修饰。(2)支化度和分子量对嵌段共聚物热性能、结晶性和亲水性的影响为考察聚合物的支化度,分子量和聚合物的热性能,结晶性能之间的相互影响,合成了一系列具有相同分子量不同支化度,和一系列具有相同支化度不同分子量的聚合物,结果表明,在相同的分子量下,随支化度升高高,熔点降低,Tg则呈现先小幅升高后大幅降低的规律,结晶温度也向低温方向移动；在相同的支化度下,随分子量的增大,熔点、Tg以及结晶温度都向高温方向移动。(3)载药微球的制备及体外释放研究以第四代哑铃型三嵌段聚合物为壁材,分别采用乳液溶剂挥发法和复乳法制备了分别用于载紫杉醇和替莫唑胺的聚合物微球,考察了制备工艺对聚合物微球的外观形貌,尺寸和载药量的影响,并研究了载药微球在磷酸盐缓冲溶液(PBS)中的体外释放曲线,结果表明,两种载药微球都具有缓释效果,且释放时间大于15天。更多还原

【Abstract】 Polyester dendrimers/dendrons with excellent biocompatibility is the one and only biodegradable dendrimer which has shown high potential in controlled drug delivery system and tissue engineerring. Divergent synthetic method has been applied in this study to synthesis the first-fourth generation macro-initiator polyethylene glycol terminated by polyester dendrons with different amounts of hydroxyl groups and the dendronized polymers based on these micro-initiators have also been investigated. The study has been divided into three parts:(1) Synthesis and study of dumbbell-shaped tri-block copolymer consisting of polycaprolactone and poly(ethylene glycol)A series of well-defined dumbbell-shaped tri-block copolymers consisting of comb-like polycaprolactone (PCL) and linear poly(ethylene glycol) (PEG) with narrow molecular weight distributions and varied PCL arm lengths have been synthesized via the sequential preparation of terminal dendronized polyhydric PEG and ring-opening polymerization of□-caprolactone (CL). The length of PCL arms can be readily controlled by the feed molar ratio of CL monomer to the hydroxyl groups in PEG macro-initiator.(2) The influence of branching degree and molecule weight on the thermol properties、crystallization and biocompatibilities.A series of copolymers with the same molecule weight and different branching degree and a series of copolymers with the same branching degree and different molecule weight were synthesized to evaluate the interrelationship of branching degree and molecule weight to thermol properties、crystallization and biocompatibilities of copolymers. And the results showed that the melting point and the crystallization temperature shifted to lower temperature with the increasing of branching degree when that series of copolymers had the same molecule weight, but the Tg of copolymers first increased within a narrow range and then decreased by a wide margin. When other series of copolymers had the same branching degree, the melting poin、Tg and crystallization temperature shifted to a higher temperature with the increasing of molecule weights of copolymers.(3) The preparation of microspheres loading drug and the study of drug release in vitro.The emulsion solvent evaporation method and the double emulsion solvent evaporation method were respectively used to prepare the copolymer microspheres loading paclitaxel and temozolomide based on the fourth generation dumbbell shaped tri-block copolymers. We evaluated the influence of preparation process of microspheres on the surface shape、size and entrapping drug amount of copolymers microspheres and studied the drug releasing curves of microspheres in PBS solution. The test results showed that both microspheres loading paclitaxel and temozolomide had the effect of controlled release and the controlled releasing time were higher than 15 days.更多还原