聚合物胶束课件.pptx

development of copolymers of poly(D,L-lactide) and methoxypolyethylene glycol as micellar carriers of paclitaxelD，L-聚丙交酯和聚乙二醇单甲醚的二嵌段共聚物制备胶束装载紫杉醇的发展introductionpaclitaxel:紫杉醇，具有卓越且广泛的抗肿瘤活性。目前临床上广泛用于转移性乳腺癌、卵巢癌等恶性肿瘤，并且在动物模型上被证明有治疗类风湿性关节炎的作用。紫杉醇具有极低水溶性，传统制剂使用聚氧乙烯蓖麻油（Cremophor EL）和无水乙醇增加溶解度及稳定性，产生过敏等严重副作用，输液系统游离出的塑化剂会加重过敏反应。两亲性二嵌段共聚物胶束可以提高疏水药物的稳定性：共价接合（化学法），直接包埋（物理法）。聚酯和聚乙二醇单甲醚二嵌段共聚物材料可生物降解，安全，被用作植入物材料和外科缝合线。疏水性的D，L聚丙交酯（PDLLA）、聚D，L丙交酯己内酯（PDLLACL）、聚乙交酯己内酯（PGACL）: 疏水内核。聚乙二醇单甲醚：亲水壳。聚合物通过开环聚合反应制备：酯环打开，与聚乙二醇单甲醚一端的羟基相连（催化剂：辛酸亚锡）。 biocompatibilitysynthesis， preparation and characterizationbiodistributionsynthesis of diblock copolymers：ring opening polymerizationD，L-lactide+ MePEG + 0.5%辛酸亚锡appropriate quantities ofglycolidcaprolactonevacuum for 20 min，heat sealedadd tomineral oil bath at 150℃ to melt10 ml glass ampouleafter meltingre-immersemineral oil bath at 150℃for 3.5hvortex mixed scale up and modify for preparation of PDLLA-MePEG copolymerreaction glassware:wash and rinse with sterile water,dry at 37℃,depyrogenation at 250℃ for at least 1h.reaction vessel:500ml,glass.round-bot-tomed-flask fitted with a ground glass stopper.reactants were stirred using a magnetic stir bar. The oil bath was maintained at 140°C and the polymerization time was 6 h. PDLLA–MePEG copolymer was stored at 2–8°C.Characterization of paclitaxel/copolymer matrix聚合物分子量估计：凝胶渗透色谱（GPC），流动相：氯仿，流速：1ml/minCMC：fluorescence intensity and anisotropy techniquesStability of paclitaxel solubilized： 5% (w:w) or 10% (w:w) in the different diblock copolymer micelles（at room temperature）：determining the time until first appearance of haziness（precipitation）in the solution.Sterilization: gamma irradiation.PDLLA–MePEG: most stable formulationsIn vivo studies: examination of acute intracutaneous reactivity in the rabbit, acute sytemic toxicity in the mouse and subchronic (14 days) intravenous toxicity in the rat.Biocompatibility of PDLLA–MePEG MicellesIn vitro test: hemolysis, genotoxicity measured, cytotoxicity.Hemoly