摘要
目的制备石杉碱甲聚乳酸-乳酸羟基共聚物微球,并评价其在大鼠体内的缓释效果。方法采用紫外分光光度法测定微球的包封率和载药量,采用透析袋法测定微球体外释放度。通过扫描电镜和显微镜观察微球的外观和表面形态,运用高效液相色谱法测定血浆浓度,采用微量羟胺法测定大鼠脑内乙酰胆碱酯酶的活性。结果微球外观圆整表面光滑。微球的粒径为63.08μm,跨距为0.73,包封率为78.08%,载药量为3.80%。石杉碱甲微球在体外可缓释21d,主要通过扩散控释机制释药,释药曲线符合Higuchi方程。大鼠肌注2.1mg微球后的最大血药浓度出现在给药后第2天,ρ_(max)为(51.47±4.70)μg·L^(-1),AUC_(0→∞)为326.11μg·d·L^(-1),MRT为8.7d。微球对大鼠皮层、纹状体和海马部位AchE活性的抑制作用可持续至给药后的第14天。石杉碱甲微球对上述3个部位AchE活性的抑制率与血浆浓度之间的关系符合Hill方程,血浓-药效的经时轨迹呈逆时针走向。结论石杉碱甲微球制备工艺简单,重现性好,体内外具有良好的缓释效果。
OBJECTIVE To prepare huperzine-A-loaded PIGA microspheres and evaluate its prolonged-release efficiency in rats. METHODS The encapsulation efficiency and drug loading were determined by UV spectrophotometer. The dialysis method was used for release analysis. The morphology of the microspheres was observed by scanning electron microscopy and microscopy. The distribution of huperzine-A within microspheres was observed by confocal laser seanning microscope. HPLC was used to determine drug plasma concentration. Microcolorimetric was used to assay acetylcholinesterase activity. RESULTS Huperzine-A microspheres possessed a smooth and round appearance. Particle diameter was 63.08 tan, span was 0.73. The encapsulation efficiency and drug loading was 78.08 % and 3.80 %, respectively. Huperzine-A-loaded PLGA microspheres controlled release for 21 d or so. Drug released from microspheres in vitro was mainly through diffusion mechanism. Release profiles conformed to Higuchi equation（ r = 0.999 7, P 〈 0.001 ）. A maximum plasma concentration of （51.47±4.70）μg·L^-1 was obtained at day 2 after microspheres were intramuscularly injected at 2.1 mg eq huperzine-A in rats. AUC0→∞ and MRT was 326.11μg·d·L^-1 and 8.7 d, respectively. Anticholinesterase effect of microspheres in rat＇s cortex, hippocampus and striatum was sustained for about 14 d. The correlation of AchE activity inhibition percentage and plasma concentration conformed to Hill equation. The relationship between pharmacokinetics and pharmacodynamics was counterclockwise hysteresis. CONCLUSION The preparation technique of huperzine-A microspheres is simple and has a good repreductivity. Microspheres have a good prolonged release effect in vitro and in vivo.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2005年第19期1496-1499,共4页
Chinese Pharmaceutical Journal
