聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的制备及体外释放***◆

背景：由聚乳酸羟基乙酸/纳米羟基磷灰石复合材料制备的微球，在体外磷酸盐缓冲液中能够持续释放药物。 目的：制备聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球，探讨纳米羟基磷灰石对复合微球的载药量、包封率和体外释放等性质的影响。 设计、时间及地点：材料学体外观察，于2009-02/2009-07在华南理工大学材料学院实验室完成。 材料：聚乳酸羟基乙酸为济南岱罡生物有限公司产品，纳米羟基磷灰石由华南理工大学特种功能材料教育部重点实验室自制，5-氟尿嘧啶为上海楷洋生物技术有限公司产品。 方法：以水溶性抗癌药物5-氟尿嘧啶作为模型药物，先用纳米羟基磷灰石吸附药物，外包裹生物相容性好且可生物降解的聚乳酸羟基乙酸，采用单乳化溶剂挥发法(S/O/W)制备聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球。对载药前后的纳米羟基磷灰石进行透射电子显微镜、扫描电子显微镜观察和FTIR分析。采用扫描电镜、激光粒度仪和紫外分光光度计对微球的理化性质及体外释药性质进行分析。 主要观察指标：纳米羟基磷灰石与5-氟尿嘧啶分子之间的相互作用，微球载药量和包封率，药物体外释放。 结果：FTIR结果表明，纳米羟基磷灰石对5-氟尿嘧啶有较强的吸附作用。聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的载药量和包封率分别为3.83%，86.78%，明显高于单纯的聚乳酸羟基乙酸-5-氟尿嘧啶微球。经过体外释放药物突释后，复合微球比单纯聚乳酸羟基乙酸微球的药物释放慢。在第27天，复合微球和单纯的聚乳酸羟基乙酸微球累积药物释率放分别为84.87%，99.87%。 结论：与单纯的聚乳酸羟基乙酸-5-氟尿嘧啶微球相比，由于纳米羟基磷灰石对5-氟尿嘧啶存在较强的吸附作用，使聚乳酸羟基乙酸/纳米羟基磷灰石-5-氟尿嘧啶复合微球的载药量和包封率得到了较大提高，具有更好的药物缓释效果。 关键词：5-氟尿嘧啶；乳酸-羟基乙酸共聚物；纳米羟基磷灰石；复合微球；药物释放 doi:10.3969/j.issn.1673-8225.2009.47.017

Preparation and in vitro release of 5-fluorouracil-loaded poly (lactic-co-glycolic-acid)/ nano-hydroxyapatite microspheres

BACKGROUND: Poly (lactic-co-glycolic-acid) (PLGA)/nano-hydroxyapatite (nHA) composite microspheres may continuously release drug in phosphate buffer solution in vitro. OBJECTIVE: To prepare 5-fluorouracil (5-Fu)-loaded PLGA/nHA microspheres, and research the effect of nHA on drug loading, encapsulation efficiency and in vitro release. DESIGN, TIME AND SETTING: An in vitro materials observation was performed at Laboratory of College of Materials Science and Engineering, South China University of Technology between February and July 2009. MATERIALS: PLGA was provided by Jinan Daigang Biomaterial Co., Ltd.; nHA by Key Lab for Special Functional Materials, Ministry of Education; 5-Fu by Shanghai Kaiyang Biomaterial Co., Ltd. METHODS: 5-Fu, a water-soluble anti-cancer drug, was used as model drug, and was firstly adsorbed by nHA and coated with biodegradable and biocompatible materials of PLGA so as to prepare PLGA/nHA-5-Fu composite microspheres by a single-emulsion solvent evaporation method (S/O/W). nHA and drug-loaded nHA were analyzed by transmission electron microscope (TEM), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). Drug loading and encapsulation efficiency as well as in vitro release of microspheres were studied with SEM, laser particle size analyzer, and UV-spectrophotometer. MAIN OUTCOME MEASURES: Interaction between nHA and 5-Fu; drug loading, encapsulation efficiency, and in vitro release of microspheres RESULTS: FTIR showed that nHA had a strong adsorption with 5-Fu. Drug loading and encapsulation efficiency of PLGA/nHA-5-Fu composite microspheres were 3.83% and 86.78%, respectively, which were significantly greater than PLGA-5-Fu microspheres. After initial burst, composite microspheres released more slowly than PLGA microspheres alone. At day 27, the cumulative release rate of composite microspheres and PLGA microspheres alone were 84.87% and 99.87%, respectively. CONCLUSION: Because nHA has a strong adsorption with 5-Fu, PLGA/nHA-5-Fu composite microspheres compared to PLGA-5-Fu microspheres alone enhances drug loading and encapsulation efficiency, and has a better drug delivery effect.