利福平乙基纤维素微球在小鼠体内的组织分布

Distribution of Rifampicin Ethylcellulose Microcapsules in Various Tissues of Mice

以有机相分散、溶媒扩散二步法制备了利福平乙基纤维素微球 ,粒径范围 2 .5～ 12 .5 μm,其中粒径 2 .5～ 5 .0 μm的约占 6 3%。采用微生物测定法研究了利福平乙基纤维素微球静脉给药后 ,利福平在小鼠体内的组织分布 ,且与游离利福平在小鼠体内组织分布进行了比较。小鼠单剂量静脉注射游离利福平或利福平乙基纤维素微球 (相当于利福平原药 ) 10 mg/ kg,测定 0 .5、1、3、7、12、2 4、48、72、12 0、16 8h共 10个时间点各组织中的药物浓度。结果表明 ,游离利福平给药组和利福平乙基纤维素微球给药组在 12 h内均以肝脏中药物浓度为最高 ,为 9.96～ 2 2 .41μg/ g,在 3h内微球给药组高于游离药物给药组 ,7、12 h微球给药组的药物浓度迅速下降 ,低于游离药物给药组 ;肾脏的药物浓度在 12 h内微球给药组明显低于游离药物给药组 ,2 4～ 16 8h微球给药组的药物浓度下降迟缓 ,显著高于游离药物给药组 ;肺脏的药物浓度始终是微球给药组高于游离药物给药组 ,12 h游离药物给药组已不能检出药物含量 ,而微球给药组直到16 8h仍维持在 5 .44μg/ g,接近游离药物给药组的最高峰值 ;血清中利福平浓度在 48h已不能检出 ,而微球给药组在16 8h为 1.33mg/ L;心脏、脾脏微球给药组和游离药物给药组的药物浓度变化无统计学意?

Ethylcellulose microcapsules containing rifampicin were prepared by the two-step method.Diameter of the microcapsules ranged from 2.5 to 12.5 μm,and the microcapsules with diameters of 2.5-5.0 μm were 63%.The levels and distribution of rifampicin ethylcellulose microcapsules were investigated in various tissues of mice by microbiological assay after iv 10 μg/g dose of free RFP of RFP encapsuled by ethylcellulose microcapsules at 0.5,1,3,7,12,24,48,72,120,168 h.The results showed that there was the highest RFP concentration in liver for the both groups within 12 hours.At 0.5,1,3 h,RFP concentration of microcapsules group in liver was higher than that of free group and at 7,12 h,RFP concentration of microcapsules group decreased quickly,less than that of free group;Within 12 h,RFP concentration of microcapsules group in kidney was clearly less than that of free group and declined slowly from 24 h to 168 h,higher notablly than free group;During all the experimental period,RFP encapsuled by ethylcellulose microcapsules had higher concentration in lung than that of free drug.RFP concentration of ethylcellulose microcapsule group in lung maintained 168 hours,whereas free RFP group maintained only 12 hours.Ethylcellulose microcapsules not only changed in vivo distribution of free RFP but also prolonged its half-life.It is concluded that RFP ethylcellulose microcapsules possess dual properties of sustained-release and targeting action.