载异烟肼利福平聚乳酸纳米粒的制备及体外释药

背景:微载体药物因具有靶向性、控释性、稳定性、更好的安全性备受关注.目的:观察载异烟肼利福平两种抗结核药于同一聚乳酸纳米粒的给药系统及体外释放特性.方法:采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,亚微粒径分析仪测定纳米粒粒径及分布,透射电镜观察其形态;高效液相色谱仪建立测定异烟肼、利福平的载药量和包封率;以磷酸盐缓冲液为释放介质,观察载异烟肼和利福平纳米粒的体外释药特性.结果与结论:载利福平和异烟肼纳米粒表面完整光滑,无明显粘连现象,纳米粒均匀度好.亚微粒径分析仪测定纳米粒平均粒径80.4 nm.异烟肼载药量为(15.95±1.34)%,包封率为(5.01±0.17)%;利福平载药量为(4.66±0.97)%,包封率为(4.05±0.18)%.体外释药结果显示纳米粒的体外释药过程较平稳.突释期纳米粒中异烟肼释放度为15.22%,到3 d累积释放度可达95.6%;利福平释放度为9.26%,到3 d累积释放度可达90.3%.提示采用改良的自乳化二元溶剂扩散法制备载异烟肼和利福平纳米粒,所得载药纳米粒的粒径小且较均匀.纳米粒体外释药过程较平稳,无明显突释现象.

Preparation and in vitro release of polylactic acid nanoparticles loaded with isoniazid and rifampicin

BACKGROUND: Micro-carrier drugs receive much concern based on their targeting, controlled-release, stability and good safety. OBJECTIVE: To study release characteristics of polylactic acid nanoparticles loaded with isoniazid and rifampicin (INH-RFP-PLA-NPs) in vitro. METHODS: INH-RFP-PLA-NPs were prepared with pusing modified spontaneous emulsification solvent diffusion method. The submicron particle size analyzer was used to detect the nanoparticle size and its distribution of INH-RFP-PLA-NPs. Observation of the morphology of INH-RFP-PLA-NPs was performed with transmission electron microscope. High performance liquid chromatography was used to detect drug loading and encapsulation efficiency. Phosphate buffer solution was used as a release medium to study the in vitro release characteristics of INH-RFP-PLA-NPs. RESULTS AND CONCLUSION: The INH-RFP-PLA-NPs were smooth and uniform without obvious adhesion. The submicron particle size analyzer showed the mean diameter was 80.4 nm. The drug loading and entrapment efficiency of isoniazid were (15.95±1.34)% and (5.01±0.17)% resectively, and those of rifampicin were (4.66±0.97)% and (4.05±0.18)% respectively. Release in vitro of INH-RFP-PLA-NPs was stable. Release rate of isoniazid was 15.22% in burst release phrase, and rose to 95.6% after 3 days; release rate of rifampicin was 9.26% and rose to 90.3% after 3 days. INH-RFP-PLA-NPs prepared by modified spontaneous binary solvent diffusion method have small and uniform mean diameter. Release in vitro of INH-RFP-PLA-NPs is stable without obvious burst release.