Ke Weilun, Zhao Yansong, Huang Rongqin, Jiang Chen, Pei Yuanying
Department of Pharmaceutics, School of Pharmacy, Fudan University, P.O. Box 130, Shanghai 200032, People's Republic of China.
J Pharm Sci. 2008 Jun;97(6):2208-16. doi: 10.1002/jps.21155.
PAMAM dendrimers can permeate across intestinal epithelial barriers suggesting their potential as oral drug carriers. In the present study, we have developed a drug-PAMAM complex for oral administration. The loading of a model drug, doxorubicin into PAMAM, the cellular uptake and pharmacokinetics of the doxorubicin-PAMAM complex were studied. As the results, the cellular uptake of doxorubicin in Caco-2 cells treated with the doxorubicin-PAMAM complex was increased significantly with an increase in concentration and time, as compared to that treated with free doxorubicin. And the transport efficiency of the doxorubicin-PAMAM complex from the mucosal side to the serosal side was 4-7 times higher than that of free doxorubicin in different segments of small intestines of rat. The doxorubicin-PAMAM complex led to the bioavailability that was more than 200-fold higher than that of free doxorubicin after oral administration. These results indicate that PAMAM dendrimer is a promising novel carrier to enhance the oral bioavailability of drug, especially for the P-glycoprotein (P-gp) substrates.
聚酰胺-胺（PAMAM）树枝状大分子能够穿透肠道上皮屏障，这表明它们作为口服药物载体具有潜力。在本研究中，我们开发了一种用于口服给药的药物-PAMAM复合物。研究了模型药物阿霉素在PAMAM中的负载情况、阿霉素-PAMAM复合物的细胞摄取和药代动力学。结果显示，与用游离阿霉素处理的细胞相比，用阿霉素-PAMAM复合物处理的Caco-2细胞中阿霉素的细胞摄取量随着浓度和时间的增加而显著增加。并且在大鼠小肠的不同节段中，阿霉素-PAMAM复合物从黏膜侧向浆膜侧的转运效率比游离阿霉素高4至7倍。口服给药后，阿霉素-PAMAM复合物的生物利用度比游离阿霉素高200多倍。这些结果表明，PAMAM树枝状大分子是一种有前景的新型载体，可提高药物的口服生物利用度，特别是对于P-糖蛋白（P-gp）底物。
