论文部分内容阅读
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 ethylene glycol chitosan-cholesterol grafts (CHGC) loaded doxorubicin (DOX) self-assembled nanoparticles and study its pharmacokinetics in rats. Methods Ethylene glycol chitosan-cholesterol grafted Doxorubicin nanoparticles (DCN) were prepared by dialysis method. Zeta potential, particle size and morphology of the drug-loaded nanoparticles were determined by dynamic light scattering particle size analyzer and atomic force microscope. The stability of DCN was investigated. The in vitro release of DCN was investigated by using phosphate buffer (PBS) as the release medium. The drug concentration of doxorubicin in rat plasma was determined by HPLC. Results With the increase of dosage, the drug loading of DCN and the potential and diameter of Ze-ta increased, and the shape of the particles was spherical. The results of in vitro release showed that the lower the pH value of the release medium, the faster the drug release and the release The results showed that the AUC (0-∞) in DCN-10 group was 5.84-fold higher than that in free DOX group (P <0.01), while the rate of DCN- MRT0-∞ in group 10 was 21.90 times more than that in DOX group (P <0.01). Conclusion CHGC, as a carrier material for macromolecular drugs, can release sustained release and pH-dependent in vitro release behavior of doxorubicin nanoparticles. DCN can stay in the blood for a long time and significantly improve the bioavailability of DOX. The results show that CHGC Nanoparticles as antitumor drug carrier has a good prospect.