摘要
目的:制备一种可用于关节腔注射的甲氨蝶呤(methotrexate,MTX)聚乳酸-聚羟基乙酸共聚物(PL-GA)缓释微球,并研究其体内外释药规律。方法:应用O/W溶剂挥发法制备MTX-PLGA微球,对其表面形态、粒径分布进行表征并测定其包封率、载药量和体内外释药谱;采用HPLC法分析药物含量;体内释放采用大鼠皮下气囊模型。结果:微球表面光滑圆整,平均粒径为(38.47±1.32)μm,包封率和载药量分别为(62.71±0.84)%和(3.23±0.13)%。体外释放t50为20 d,体外释放速率常数Kr=0.038μg.mL-1.d-1。体内试验显示,在气囊中的释放速率常数KR=0.12μg.mL-1.d-1。结论:采用本法制备的MTX-PLGA微球具有明显的缓释作用,有望成为一种有效的治疗类风湿关节炎的制剂。
Objective ： To prepare methotrexate （MTX） loaded poly （DL-lactide-co-glycolide） （PLGA） microspheres for intra-articular administration and investigate their release profiles. Methods： Microspheres were prepared by oil-in-water emulsion solvent evaporation method. The surface morphology, size distribution, drug loading content and the encapsulation efficiency of microspheres were examined. The in vitro drug release profiles of the microspheres were measured in phosphate buffer saline （PBS, pH 7.40） , and a rat air-pouch model was utilized to determine the in vivo drug release properties. The drug concentration was assayed by high performance liquid chromatography （ HPLC）. Results： The MTX loaded microspheres had smooth surface with narrow size distribution and the average particle size was （38. 47 ± 1. 32 ）μm. The drug loading content and encapsulation efficiency were （3. 23±0. 13） % and （62.71 ± 0.84） % , respectively. The drug release rate constant of microspheres in vitro and in vivo were 0. 038/μg· mL^-1· d^-1 and 0.12/μg· mL^-1· d^-1, respectively. Conclusion： The MTX-PLGA microspheres show evidently sustained release effect and may be used as a potential drug delivery sys- tem for treatment rheumatoid arthritis.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第15期1187-1191,共5页
Chinese Journal of New Drugs
基金
国家重点科学研究计划项目(2006CB933300)
博士点基金(96002323)
厦门市科技计划项目(3502Z20055007)
