快速膜乳化法制备载紫杉醇聚乳酸类微球的研究

发布时间：2018-03-06 09:09

本文选题：快速膜乳化　切入点：微球　出处：《北京化工大学》2010年硕士论文　论文类型：学位论文

【摘要】： 微球作为难溶药物的传输载体因其具有增加难溶药物溶解性、增强透膜吸收,靶向传输等优势而成为目前研究的热点之一。为了解决传统方法所制备的微球粒径不均一的问题,本论文采用快速膜乳化法制备了粒径均一、可控的载难溶药物紫杉醇的聚乳酸(Polylactic acid,PLA)、聚乳酸-羟基乙酸共聚物[Poly (lactic-co-glycolic acid), PLGA]和聚(乳酸-聚乙二醇)二嵌段共聚物[(Monomethoxypoly(ethylene glycol)-b-poly-DL-lactic acid), PELA]微球,并对三种载药微球的表面形貌、药物分布、药物载药率和包埋率及体外释药行为进行系统考察和比较。本论文工作分为三部分。第一部分采用快速膜乳化法制备PLA空白微球,通过制备条件优化,制备得到了粒径为900-1000 nm的均一的微球,多分散系数为0.005,与传统均质、超声法制备的微球进行比较,结果表明,快速膜乳化法制备的微球均一性大大优于传统方法。在此基础上,还制备了同样粒径的均一PLGA和PELA微球,形貌表征结果表明,PLA和PLGA微球球形圆整、表面光滑,而PELA微球表面出现褶皱,有类似孔道的结构。第二部分在第一部分工作的基础上制备了均一的载紫杉醇PLA、PLGA和PELA微球,并对载药率、包埋率、药物在微球中的分布及体外释药行为进行表征和比较。结果表明PLA、PLGA和PELA微球对紫杉醇的装载率分别为3.89%、4.93%和3.18%,包埋率分别为63.2%、71.6%和51.3%,紫杉醇在PLA微球中以细小的的颗粒较均匀的分布,在PLGA微球中以较小的块状分布,而在PELA中则以较大的块状分布。在磷酸盐缓冲液中释放60天后,PLGA微球的药物释放率为83.87%,PLA微球的药物释放率为50.25%,PELA微球的药物释放率为41.27%。第三部分尝试对微球的结构进行调控,以NH4CO3为内水相添加剂制备多孔PLA微球,考察了内水相盐浓度、制备初乳时超声破碎功率、时间以及油相乳化剂对微球结构的影响。通过本论文的比较研究表明,与均质乳化法和超声破碎法相比,在制备均一的微球方面,快速膜乳化法具有明显的优势。对PLA、PLGA和PELA载紫杉醇聚乳酸类微球,因材料亲疏水性不同导致的难溶药物在微球内的分布不同,最终导致不同材料微球对药物装载率、包埋率及体外释药行为有所不同,只有亲水性适中的PLGA材料对药物有较高的药物装载率和包埋率,同时,因亲水性适中导致其体外释放也较快,有望成为合适的难溶药物载体材料。
[Abstract]:As the transport carrier of insoluble drugs, microspheres have become one of the hot research topics because of their advantages of increasing the solubility of insoluble drugs, enhancing the absorption of permeable membrane, and targeting transport, etc. In order to solve the problem of uneven particle size of the microspheres prepared by traditional methods, In this paper, a uniform and controllable poly (lactic acidacido) PLA, Poly lactic-co-glycolic acididate (PLGA) and poly (lactic acid polyethylene glycol) diblock copolymer (PELA) microspheres were prepared by rapid membrane emulsification. The surface morphology, drug distribution, drug loading rate, drug entrapment rate and in vitro drug release behavior of the three drug loaded microspheres were systematically investigated and compared. The work of this paper is divided into three parts. In the first part, the PLA blank microspheres were prepared by rapid membrane emulsification method. By optimizing the preparation conditions, the homogeneous microspheres with the diameter of 900-1000 nm were prepared, and the polydispersity coefficient was 0.005, which was homogenized with the traditional microspheres. The results show that the homogeneity of the microspheres prepared by rapid membrane emulsification is much better than that of the traditional method. On this basis, homogeneous PLGA and PELA microspheres of the same size have also been prepared. The results of morphology characterization showed that the microspheres of PLA and PLGA were spherical and smooth, while the surface of PELA microspheres was ruffled and had a pore like structure. In the second part, uniform paclitaxel loaded PLA PLGA and PELA microspheres were prepared on the basis of the work of the first part. And the drug loading rate, entrapment rate, The drug distribution in microspheres and drug release behavior in vitro were characterized and compared. The results showed that the loading rates of paclitaxel in PLGA and PELA microspheres were 3.89% 4.93% and 3.18%, respectively, and the entrapment rates were 71.6% and 51.3%, respectively. Paclitaxel in PLA microspheres was very fine. A more uniform distribution of particles, In PLGA microspheres, they are distributed in smaller blocks, The drug release rate of PLGA microspheres in phosphate buffer solution was 83.87. The drug release rate of PLGA microspheres was 50.25 and 41.27.The third part attempted to regulate the structure of microspheres. Porous PLA microspheres were prepared with NH4CO3 as internal aqueous phase additive. The effects of concentration of salt in inner water, ultrasonic crushing power, time and emulsifier of oil phase on the structure of microspheres were investigated. Compared with homogeneous emulsification method and ultrasonic crushing method, rapid membrane emulsification method has obvious advantages in the preparation of homogeneous microspheres. PLGA and PELA loaded paclitaxel polylactic acid microspheres were studied. The distribution of insoluble drugs in the microspheres was different due to the different hydrophobicity of the materials, which resulted in different drug loading rate, entrapment rate and drug release behavior in vitro. Only the PLGA with moderate hydrophilicity has higher drug loading rate and entrapment rate. At the same time, due to the moderate hydrophilicity, its release in vitro is also faster, so it is expected to be a suitable drug carrier material.
【学位授予单位】：北京化工大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：TQ460.1

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