载多柔比星的胆固醇修饰乙二醇壳聚糖纳米粒在荷S180瘤小鼠的组织分布

Tissue Distribution of Doxorubicin-Loaded Nanoparticles Based on Cholesterol-Modified Glycol Chitosan in S180-Bearing Mice

目的研究载多柔比星(DOX)的胆固醇修饰乙二醇壳聚糖纳米粒(DCN-16)在荷S180瘤小鼠体内的组织分布。方法将多柔比星和DCN-16分别给动物静脉注射给药,用高效液相色谱法测定荷瘤小鼠不同组织中多柔比星的含量,对药物的体内分布特征和靶向性进行评价。结果 DCN-16能够长时间滞留在小鼠血液中,在荷瘤鼠中的心、肺、肾中的血药浓度-时间曲线下面积(AUC0→∞)比多柔比星组显著减小(P<0.05),在肝、脾和肿瘤组织中的AUC0→∞显著增多(P<0.05)。DCN-16在肿瘤中的相对摄取率(Re)为2.56。结论应用胆固醇修饰乙二醇壳聚糖纳米粒负载多柔比星后,能够使药物在血液中长时间循环,增加肿瘤靶向治疗效果和降低心脏的毒副作用。

OBJECTIVE To study the tissue distribution of doxorubicin-loaded cholesterol-modified glycol chitosan nanoparticles （named as DCN-16） in S180-bearing mice. METHODS After intravenous administration of doxorubicin （DOX） or DCN-16, DOX concentrations in plasma and tissues samples which were collected at predetermined time were determined by high performance liquid chromatography （HPLC）. And DOX distribution and targeting performance in vivo were evaluated. RESULTS DCN-16 displayed long circulation time in S180-bearing mice. The area under the curve （AUC0→∞ ） of DCN-16 was lower in heart （P 〈 0. 05 ）, lung （P 〈 0. 05 ） and kidney （P 〈 0. 05 ） than that of free DOX. In addition, compared with free DOX, DCN-16 also produced significantly increased drug accumulation in liver （ P 〈 0. 05 ）, spleen （ P 〈 0. 05 ） and tumor （ P 〈 0. 05 ）. The relative tissue exposure （ Re ） of DCN-16 in tumor was 2. 56-folds of free DOX. CONCLUSION Encapsulating DOX with cholesterol-modified glycol chitosan nanop- articles can prolong the systemic circulation time of DOX, increase its anti-tumor targeting activity and reduce its cardiac toxicity.