Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system

✍ Scribed by Weilun Ke; Yansong Zhao; Rongqin Huang; Chen Jiang; Yuanying Pei

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 271 KB
• Volume: 97
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.21155

✦ Synopsis

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.