Abstract
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.
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