目的制备粒径均一的利福布丁聚乳酸-羟基乙酸共聚物微球，并对其进行表征。方法分别采用快速膜乳化及均质乳化法制备微球，并对2种制备方法所得微球的粒径均一性进行了比较。通过正交设计优化制备条件，得到快速膜乳化制备的最优处方，并对其载药量、包封率、体外释放进行了考察。结果均质乳化法制备的微球的平均粒径为(4242±175.6)nm，PDI为0.330。而快速膜乳化法制备的微球平均粒径为(1330±64)nm，多分散系数(PDI)为0.168，且微球形态光滑圆整、粒径均一。通过处方优化，快速膜乳化制备微球的载药量为(46.83±0.29)%，包封率为(93.66±0.58)%，体外15d累积释药率约为66%。结论快速膜乳化法制备的利福布丁微球粒径均一可控，且具有较高的包封率和载药量，在体外能缓慢释放无突释，是一种较好的制备聚乳酸-羟基乙酸共聚物微球的方法。
Abstract
OBJECTIVE To prepare uniform-sized rifabutin-loaded PLGA microspheres and evaluate the characteristics of the microspheres. METHODS The particle size uniformity of the microspheres prepared by premix membrane emulsification method and homogenization method was compared. Preparation technology was optimized by orthogonal design. Then the drug loading, entrapment efficiency and in vitro drug release were studied. RESULTS The average particle size and PDI of the microspheres prepared by homogenization method were (4 242?175.6) nm and 0.330. The microspheres prepared by premix membrane emulsification method were round, complete and smooth, and their particle sizes were well-distributed with mean value of (1 330?64) nm and PDI of 0.168. Besides, the drug loading was (46.83?0.29)% and the entrapment efficiency was (93.66?0.58)%. Accumulative drug release rate was 66% in 15 d. CONCLUSION The rifabutin-loaded PLGA microspheres prepared by premix membrane emulsification method have narrow particle size distribution, high drug loading, high entrapment efficiency, and ideal in vitro sustained-release effect.
关键词
利福布丁 /
快速膜乳化 /
聚乳酸-羟基乙酸共聚物微球
{{custom_keyword}} /
Key words
rifabutin /
premix membrane emulsification /
PLGA microsphere
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] OHASHI K, KABASAWA T, OZEKI T, et al. One step preparation of rifampicin/poly( lactic-co-glycolicacid) nanoparticle containing mannitol microspheres using a four fluid nozzle spray drier for inhalation therapy of tuberculosis . J Controlled Release, 2009, 135(1): 19-24.
[2] SHI R R, GAO F X,WANG J D, et al. A preliminary investigation of rifampin liposome in treatment of tuberculosis in mice . J Med Res(医学研究杂志), 2008,37(5): 42-43.
[3] ZHANG W G, JIANG X T, ZHU C J, et al. The study of RFP-PLA-microspheres for lung targe . Acta Pharm Sin(药学学报), 1998, 33(1): 57-66.
[4] ROLEE S, AWADH B Y, PAVAN M, et al. Inhalable microparticles modify cytokinesecretion by lungmacrophages of infected mice . Tuberculosis, 2011, 91 (1):107-110.
[5] HU C H, FENG H Z, ZHU C Y. Preparation and characterization of rifampicin-PLGA microspheres/sodium alginate in situ gel combination delivery system . Colloids Surf B Biointerfaces, 2012, 15(95):162-169.
[6] JOSEPH S, BUNJES H. Preparation of nanoemulsions and solid lipid nanoparticles by premix membrane emulsification . Pharm Sci, 2012, 101(7):2479-2489.
[7] WEI Q, WEI W, TIAN R, et al. Preparation of uniform-sized PELA microspheres with high encapsulation efficiency of antigen by premix membrane emulsification . Colloid Interface Sci, 2008, 323(2):267-273.
[8] WEI Q, WEI W, LAI B, et al. Uniform-sized PLA nanoparticles: Preparation by premix membrane emulsification . Int J Pharm, 2008, 359(1-2):294-297.
[9] BARLUENGA J, AZNAR F, GARC A AB, et al. New rifabutin analogs: Synthesis and biological activity against Mycobacterium tuberculosis . Bioorg Med Chem Lett, 2006, 16(22): 5717-5722.
MCGREGOR M M, OLLIARO P, WOLMARANS L, et al. Efficacy and safety of rifabutin in the treatment of patients with newly diagnosed pulmonary tuberculosis . Am J Respir Crit Care Med, 1996, 154(5): 1462-1467.
GISBERT J P, CASTRO-FERNANDEZ M, PEREZ-AISA A, et al. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures . Aliment Pharmacol Ther, 2012, 35(8):941-947.
HAN X Q, HUANG H R, LI Y J, et al. Analysis of the antimycobacterial activities of rifabutin and the relationship between drug-resistance and rpoB mutations of Mycobacterium tuberculosis . Chin J Tubercul Resirat Dis(中华结核和呼吸杂志), 2011,34(10):762-765.
USP32-NF27 (美国药典32版-国家处方集27版) . 2009:3499-3500.
FENG H Z,ZHANG L M,ZHU C Y. Genipin crosslinked ethyl cellulose-chitosan complex microspheres for anti-tuberculosis delivery . Colloids and Surfaces B: Biointerfaces,2013,103:530-537.
TIAN R, WANG L Y, WU J, et al. Preparation of uniform size PLGA microparticles and microcapsules by premix membrane emulsification . Chin J Process Eng(过程工程学报),2009,9(4):754-762.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家科技重大专项(2012ZX10003009-001-002)
{{custom_fund}}
PDF(927 KB)
