生物降解性psa peg-psa的合成及其用作药物载体的初步研究-synthesis of biodegradable psa peg - psa and its application as drug carrier.docx

PAGE PAGE 10 束的粒径和多分散指数，结果显示三种方法均可以制得胶束。三种方法 制备的胶束有共同的趋势，就是对同一种类型的共聚物来说，疏水链段 越长，形成的胶束粒径就越大。采用沉淀/溶剂挥发法制备的胶束粒径 数据表明，有机溶剂的种类、共聚物在有机相中的浓度和共聚物滴加进 入水相的速度等因素对胶束的大小都有影响。原子力显微镜图像表明， 共聚物胶束为粒径均匀的球形胶束。 分别向 PSA-PEG-PSA 共聚物胶束溶液中加入不同浓度的无机盐 （NaCl 和 Na2SO4），测定溶液的吸光度，研究了无机盐对共聚物胶束的 盐效应。实验结果表明，不同的无机盐对胶束溶液的影响程度不同，无 机盐离子的脱水作用越大，对共聚物胶束的稳定性影响就越大。在共聚 物胶束溶液中，加入等体积兔血浆后，共聚物胶束对无机盐（Na2SO4） 脱水作用的耐受性增强，稳定性提高。 以双嘧达莫(dipyridamole，DP)为模型药物，采用沉淀/溶剂挥发法， 制备 PSA-PEG-PSA 三嵌段共聚物载药胶束。采用 DLS 测定胶束的粒径， 载药胶束粒径大于相应的空白胶束。随着共聚物中疏水链段比例的增 加，胶束的载药量和包封率都上升，而且其药物释放时间延长。 关键词：PSA，PEG-PSA，两亲性嵌段共聚物，生物降解性，胶束，药 物释放 SYNSESIS AND PRIMARY STUDY OF BIODEGRADABLE POLY(SEBACIC ANHYDRIDE) AND POLY(ETHYLENE GLYCOL)-POLY(SEBACIC ANHYDRIDE) BLOCK COPOLYMERS AS DRUG CARRIERS ABSTRACT In recent years, biodegradable polymeric materials have been found to be useful in drug delivery, bone and cartilage repair, and tissue engineering applications. In these materials, polyanhydride was a kind of biodegradable polymer, which attracted the interest of many researchers, because it was biocompatible and the rate of degradation was easily controlled. In this dissertation, poly(sebacic anhydride) (PSA, Mn = 40,000)) was synthesized. Besides the homopolymer, diblock, triblock, 3-armed, and 4-armed poly (ethylene glycol)-co-poly(sebacic anhydride) block copolymers were also synthesized. Except the diblock copolymers, the others have not been reported yet. The self-aggregation behaviors of these copolymers in aqueous solution were studied. Furthermore, drug release profiles from the PSA microspheres and copolymer micelles were studied. PSA prepolymers were synthesized with acetyl anhydride and sebacic acid. The chemical structure of prepolymer was characterized with 1H NMR, 13C NMR and FTIR, and the results confirmed that the product had the expected structure. In addition, the elementary composion obtained by elementary analysis was close to the result calculated from 1H NMR. Poly(sebacic anhydride) was synthesized with PSA prepolymers by melt-po