Enhanced oral bioavailability of doxorubicin in a dendrimer drug delivery system.
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.
Ke
Weilun
W
Department of Pharmaceutics, School of Pharmacy, Fudan University, P.O. Box 130, Shanghai 200032, People's Republic of China.
Zhao
Yansong
Y
Huang
Rongqin
R
Jiang
Chen
C
Pei
Yuanying
Y
D000284:Administration, Oral; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D018938:Caco-2 Cells; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D050091:Dendrimers; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010539:Permeability; D011073:Polyamines / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011073:Polyamines; D004317:Doxorubicin