摘要
目的制备乙二醇壳聚糖-胆固醇接枝物(CHGC)载多柔比星(DOX)自聚集纳米粒,并考察其在大鼠体内的药动学行为。方法采用透析法制备乙二醇壳聚糖-胆固醇接枝物载多柔比星纳米粒(DCN);应用动态光散射粒度仪和原子力显微镜测定载药纳米粒的Zeta电位、粒径与形态,考察DCN的稳定性;以pH(5.5,6.5,7.4)磷酸盐缓冲溶液(PBS)作为释放介质,考察DCN的体外释放行为;采用HPLC测定多柔比星在大鼠血浆中的药物浓度。结果随着投药量的增加,DCN的载药量、Ze-ta电位和粒径增大;粒子形态呈球形;体外释放实验结果表明,释放介质的pH值越低,药物释放越快,且释放速率随着纳米粒载药量的增大而降低;大鼠体内药动学实验结果表明,DCN-10组的AUC(0-∞)是游离DOX组的5.84倍(P<0.01);DCN-10组的MRT0-∞是DOX组的21.90倍(P<0.01)。结论CHGC作为高分子药物载体材料,载多柔比星纳米粒的体外释放行为具有缓释和pH依赖特征;DCN能够在血液中长时间滞留,明显提高DOX的生物利用度,结果表明,以CHGC纳米粒作为抗肿瘤药物载体具有较好的应用前景。
OBJECTIVE To prepare doxorubicin（DOX） loaded self-aggregated nanoparticles based on cholesterol-modified glycol chitosan conjugate（CHGC）and study its pharmacokinetics in rats. METHODS DOX was physically entrapped into the CHGC nanoparticles by a dialysis method. The characteristics of DOX-loaded CHGC （DCN） nanoparticles were analyzed using dynamic lightscattering（DLS） and atomic force microscope （AFM）. The stabihty of DCN nanoparticles was investigated at 37 ℃in phosphate buffered （PBS） at pH 7.4. The release of DOX from the DCN nanoparticles was studied in vitro by a dialysis method in PBS （ pH 5. 5, 6. 5 and 7.4 ）. The concentration of DOX in rats plasma was determined by high-performance liquid chromatography （HPLC）. RESULTS The DCN nanoparticles were almost spherical in shape. Their size and Zeta potential were increased with the increase of DOX-loading content. The in vitro release behavior of DOX from the DCN nanoparticles was pH-dependent. DOX release from the low drug-loading nanoparticles was also much faster than drug release from higher drug-loading nanoparticales. In rat pharmacokinetic study, the AUC（0-∞）of DCN -10 was 5.84 times as the value of DOX（P 〈 0. 01 ）. Moreover, MRT0-∞ of DCN-10 was increased by 20. 90 times than that of DOX（P 〈 0.01 ）. CONCLUSION CHGC nanoparticles could be used as a drug carrier. The drug release from the DCN nanoparticles was in sustained and pH-dependent manner. Moreover, DCN delayed release compared with free DOX. These results showed that DCN could improve the bioavailability of DOX significantly. Therefore, CHGC has a good prospect of application in drug delivery system for cancer therapy.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第4期277-282,共6页
Chinese Pharmaceutical Journal
关键词
乙二醇壳聚糖-胆固醇接枝物
多柔比星
自聚集纳米粒
药动学
cholesterol-modified glycol chitosan conjugate
doxorubicin
self-aggregated nanoparticles
pharmacokinetics
