【作者】 张磊；

【导师】 蔡晴；

【作者基本信息】 北京化工大学 ， 材料科学与工程， 2010， 硕士

【摘要】 高分子胶束粒径较小,一般不超过100nm,具有纳米材料的特性,是近几年正在发展的一类新型的药物载体,其载药范围广、结构稳定、具有优良的组织渗透性,体内滞留时间长,能使药物有效地到达靶点。而如何使其带有智能靶向性以及怎样减弱其初期爆发释放行为成为了最近研究的热点。本研究中,制备出了具有温度响应性的纳米胶束,并得到了具有不同核交联度的载药胶束,并对其药物释放行为进行了研究。主要工作如下：1、本研究利用两步聚合法合成了含有带端羟基的聚(N-异丙基丙烯酰胺-cO-N,N-二甲基丙烯酰胺)亲水段和聚己内酯疏水段的两亲性嵌段共聚物P(NIPAAm-co-DMAAm)-b-PCL。以巯基乙醇为链转移剂,通过调节巯基乙醇和单体的比例,以及NIPAAm和]DMAAm的比例,可以做到对P(NIPAAm-co-VMAAm)的分子量和低临界溶液温度(LCST)的调控。在异辛酸亚锡的催化下,再利用其端羟基引发己内酯开环聚合。进一步用丙烯酰氯和该嵌段共聚物的端羟基反应,得到PCL链末端带有丙烯酰基官能团的嵌段共聚物。2、将端羟基和端丙烯酰基的P(NIPAAm-co-DMAAm)-b-PCL按不同比例混合得到的胶束,经光引发交联后得到具有不同核交联密度的胶束。将疏水性药物紫杉醇载入上述胶束中,在37℃或43℃进行药物释放试验。结果表明,P(NIPAAm-co-DMAAm)-b-PCL嵌段共聚物胶束对紫杉醇的释放有一定的温度敏感性；PCL核交联程度对紫杉醇释放的影响更为明显,随着核交联程度的提高,紫杉醇的释放速度减慢,而且,对初期的爆发释放行为有了明显的减弱。生物可降解的两亲性嵌段共聚物P(NIPAAm-co-DMAAm)-b-PCL形成的核交联的温敏性高分子胶束低临界溶液温度约为42℃,具有较好的药物包覆及释放性能,有可能结合实体肿瘤的局部过热治疗,用于对肿瘤的靶向给药治疗。更多还原

【Abstract】 The sizes of polymeric micelles are generally less than 100nm. With the characteristics of nano-materials they are being researched as drug carriers in recent years. Polymeric micelles have the features of structural, stability, excellent tissue permeability, long residence time in vivo, and they also can effectively reach the target drugs. To develop new kind of polymeric micelles for target drug delivery and to decrease the initial burst release are the major two issues in this area. In this study, we produced thermo-sensitive nanoscale micelles with different core-crosslinkings, and their drug release behaviors were studied. Main tasks are listed as follows:1, In this study we used the two-step polymerization to produce the poly(N-isopropylacrylanide-co-N,N-dimethylacrylanide)-b-poly(-capr olactone) block copolymers (P (NIPAAm-co-DMAAm)-b-PCL). At first with mercaptoethanol as chain transfer agent, and by adjusting the monomer ratio of NIPAAm and DMAAm, the molecular weight and lower critical solution temperature (LCST) of P (NIPAAm-co-DMAAm) can be controlled. Then, caprolactones were ring-polymerized by the hydroxyl endgroup of P (NIPAAm-co-DMAAm) by using stannous octotate as catalyst to obtain hydroxyl-terminated P (NIPAAm-co-DMAAm)-b-PCL. By reacting with acryloyl chloride, the hydroxyl endgroups were changed into acryloyl endgroups.2, Hydroxyl-terminated and acryloyl-terminated of P(NIPAAm-co-DMAAm)-b-PCL were mixed to get polymeric micelles with the different degrees of core crosslinking. The hydrophobic drug was paclitaxel loaded in the micelles, and the temperatures of the drug release tests were setting at 37℃or 43℃. The results showed that the drug release from the micelles exhibifed a certain themosentivity. The cross-linking degrees had a more remarkable effect paclitaxel release. With the cross-linking degree of increase, the release of paclitaxel slowed down, and the initial burst release was reduced. The results of the present study show that the micelles based on thermosentive P(NIPAAm-co-DMAAm)-b-PCL with a LCST around-40℃maybe able to realize a thermo-responsive release behavior at temperatures above and below LCST. Furthermore, the core-crosslinking method can be used to increase the stability of micelles and adjust the drug release rates. With further deep investigation, this kind of thermosensitive micelles can have potential use as carriers for hydrophobic anticancer agents targeted for solid tumor therapy with local hyperthermia therapy.更多还原