多柔比星白蛋白微球的生物性质及其在大鼠体内的分布

目的:研究多柔比星(DR)白蛋白微球生物性质及其在大鼠体内的分布。方法:采用胰酶降解法研究微球的生物降解性能并确定交联剂浓度及固化时间与其降解时间的关系;应用透析法研究DR白蛋白微球和DR水溶液的体外溶出/释药性;测定大鼠尾静脉分别注射DR白蛋白微球和DR水溶液2.5 mg·kg~(-1)后体内各组织中分布浓度。结果:降解时间随交联剂浓度和交联时间增加而延长,固化时间以90 min为宜;DR水溶液在6 h内溶出完全,微球混悬液在168 h释放量仅达80%;微球组的DR在肝和脾中分布浓度显著高于水溶液组(P<0.01),其它组织中则低于水溶液组。结论:DR白蛋白微球具有明显的缓释作用,对肝和脾表现出显著靶向性,对心脏具有很低的亲和性。

Biological Property and Tissue Distribution of Doxorubicin Albumin Microspheres in Rats

OBJECTIVE： To investigate the biological property of doxorubicin albumin microspheres （DR-HAS-MS） and its tissue distribution in the rats. METHODS： Pancreatin degradation method was applied to determine the biodegradation property of DR- HAS MS as well as the correlation between the cross linking agent concentration and the degradation time and between the setting time and the degradation time. The dialysis method was applied to study the in vitro drug dissolution/ release characteristics of DR - HAS - MS vs. DR solution. DR concentrations in different tissue of rats at different time following intravenous DR HAS- MS vs. DR solution （at a dose of 2.5 mg · kg^ -1） were determined. RESULTS： The degradation time increased with the increase of cross linking agent concentration and cross - link time. The optimal setting time was 90 min. Within 6 hours the dissolution ratio of DR from DR solution was 100%, while the releasing ratio of DR from DR- HAS- MS suspension was only 80% within 168 hours; DR concentrations in the liver and the spleen in the DR- HAS- MS group were significantly higher than in DR solution group （P 〈 0.01）, while in other tissues, DR concentrations were lower in the DR - HAS - MS group. CONCLUSION ： DR - HAS - MS possess remarkable sustained - release effect and targeted released in liver and spleen but very low affinity to heart.