紫杉醇纳米粒-微球系统的研制

Preparation of taxol nanoparticals-in-microsphere system

目的制备紫杉醇纳米粒-微球系统(taxol nanoparticals-in-microsphere system,TAX-NiMS),并考察其体外释放特性。方法以聚乳酸-羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)为载体,采用乳化溶剂挥发法制备紫杉醇纳米粒(taxol nanoparticals,TAX-NPs)。以包封率、载药量及粒径为考察指标,采用单因素试验法优化处方。采用内源乳化凝胶法,以海藻酸钙为包裹材料,制备包覆TAX-NPs的微球系统。在扫描电镜和透射电镜下观察TAX-NiMS的表面和内部形态,并测定其粒径及体外释放特性。结果纳米粒优化处方:PLGA质量浓度为100 g·L-1,聚乙烯醇质量浓度为10 g·L-1,油相与水相体积比为1∶10,超声功率为300 W。微球优化处方:海藻酸钠(NaALG)质量浓度为15 g·L-1,Span-80质量浓度为10 g·L-1,Ca CO3与Na ALG质量比为1∶3,油相与水相体积比为1∶5。此条件下制备的TAX-NiMS的包封率、载药量和平均粒径分别为(84.33±1.11)%、(1.12±0.15)%和(2.678±0.014)μm。TAX-NiMS的12h释放量仅达到16.51%。结论 TAX-NiMS的制备方法稳定可控,且突释效应显著减小,为药物新剂型的开发提供了思路。

Objective To prepare taxol nanoparticals-microsphere system（TAX-NiMS） and evaluate its drug release characteristics in vitro.Methods TAX nanoparticals（TAX-NPs） were prepared by emulsion solvent evaporation method with poly（lactic-co-glycolic acid）（PLGA） as carrier.Single factor test was used to optimize the formulation of TAX-NPs,which took the encapsulation efficiency,drug loading and particle size as evaluation parameters.TAX-NiMS were prepared cladding TAX-NPs with calcium alginate as carriers by emulsification/internal gelation.TAX-NiMS external and internal morphology were observed by SEMand TEM,and particle sizes and the release characteristics in vitro were evaluated.Results The optimized formulation of TAX-NPs was as follows： PLGA was 100 g·L^-1,PVA was 10 g·L^-1,O /W was 1∶10（V∶ V）,and ultrasonic power was 300 W.The optimized formulation of microspheres was as follows： Na ALG was15 g·L^-1,Span-80 was 10 g·L^-1,Ca CO3/ Na ALG was 1∶ 3（m∶ m）,and O/W was 1∶ 5（V ∶ V）.The encapsulation yield,drug loading and mean particle size of TAX-NiMS prepared in these conditions were（84.33 ±1.11） %,（1.12 ± 0.15） %,and（2.678 ± 0.014）μm,respectively.The accumu-lative drug release amount in 12 h was 16.51%.Conclusions The preparation method of TAX-NiMS is stable and reliable,and the burst release of TAX-NiMS is evidently decreased,which provides a newway to develop newdosage form.