【作者】 毛娟；

【导师】 何应；

【作者基本信息】 天津大学 ， 药剂学， 2007， 硕士

【摘要】 纳米粒给药系统是一种非常有前途的新型药物投递和控释系统,与传统剂型相比,具有许多无法比拟的优越性。由于聚乳酸及其共聚物具有独特优良的生物相容性和可生物降解性,被广泛应用于控释给药系统的研究,本课题的研究目的就是选用聚乳酸-羟基乙酸共聚物(PLGA)作为载体材料,对载水溶性药物纳米粒的制备工艺进行研究优化并进行体外评价,为其能在今后的临床应用中发挥作用奠定基础。5-氟尿嘧啶(5-Fu)属抗代谢类的抗癌药,在体内代谢快,半衰期短,具有较大的毒副作用;临床上为了达到有效的体内血药浓度,往往采用大剂量、持续给药或反复多次给药等途径,这大大增加了5-Fu的用药危险和毒副作用。因此,有必要开发新型5-Fu缓释制剂。本文以5-Fu为模型药物,采用优化改进的复乳法(W/O/W)制备载5-Fu的PLGA纳米粒,并对纳米粒的粒径、形貌、包封率、载药量、体外释放等进行考察与评价。探讨一条适合于制备此类药物纳米粒的有效工艺,通过对制备工艺条件的优选,SEM和TEM对载5-Fu的PLGA纳米粒表面形貌和粒径分布等进行表征,紫外分光光度法对纳米粒的载药量、包封率进行检测,证明在最优条件下制备的纳米粒呈规则圆形,表面光滑,粒径分布均一,粒径范围在100~200nm,最高载药量和包封率可达到10.02%和36.06%。在载药纳米粒制备工艺优选的基础上,采用紫外分光光度法测定载药纳米粒药物的体外释放行为,结果表明:纳米粒对5-Fu的缓释作用明显,释放周期比较长且温和平缓,可作为5-Fu的理想载体。在对水溶性药物包裹的基础上,将纳米粒给药系统应用于蛋白多肽类药物,以期开拓新的给药途径,实现蛋白多肽类药物的口服给药,通过对蛋白模型药物牛血清白蛋白(BSA)进行包裹,并通过方法学验证,得到了包封率和载药量比较理想的结果。更多还原

【Abstract】 Nanoparticles(NPs) is a very promissing drug delivery system, which possesses many advantages over the traditional drug delivery systems. Polylactide(PLA) and Polylactide-co-glycolide(PLGA) have been applied widely in the control release preparation field. The purpose of this study is to research the drug loaded Polylactide-co-glycolide Nanoparticles (PLGA-NPs), optimizing the technology and evaluating the release behavior in the vitro, which is contribute to clinic application in the future.5-fluorouracil(5-Fu) loaded PLGA-NPs were prepared by improved double emulsion (water-in-oil-in-water, W/O/W) method. The characters of the NPs were measured by SEM, TEM, and the entrapment efficiency and drug loading of 5-Fu loaded PLGA-NPs was investigated via UV method. The results showed that NPs prepared by the best condition were spherical in shape, and the particles diameters ranged from 100-200nm. The entrapment efficiency and drug loading was 36.03% and 10.02% respectively.The release behavior of 5-Fu NPs was investigated via UV method. It was found that the release of 5-Fu from NPs had three periods, i.e., burst release, sustained release and last release period, and the NPs had a good sustained release effect on the 5-Fu.Based on the research on the water-soluble anti-cancer drug loaded PLGA-NPs, the peptide drug delievery system was also studied. BSA loaded PLGA-NPs were prepared, and it showed that the NPs can be also applied to the peptide drug.更多还原