Potential oral delivery of 7-ethyl-10-hydroxy-camptothecin (SN-38) using poly(amidoamine) dendrimers.
OBJECTIVE
To investigate potential application of poly(amidoamine) (PAMAM) dendrimers for improving the delivery of SN-38.


METHODS
Complexes of SN-38 with generation 4 amine terminated PAMAM dendrimers were synthesized with varying amounts of drug. Stability of the complexes as well as influence of complexation on permeability across and cellular uptake by Caco-2 cells was evaluated.


RESULTS
The complexes were stable at pH 7.4 and drug was released at pH 5. A tenfold increase in permeability and more than hundredfold increase in cellular uptake of the complexes with respect to free SN-38 was observed.


CONCLUSIONS
Studies suggest that complexation with PAMAM dendrimers has the potential to improve the oral bioavailability of SN-38.
Kolhatkar
Rohit B
RB
Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Baltimore, Maryland, USA.
Swaan
Peter
P
Ghandehari
Hamidreza
H
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D050091:Dendrimers; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D000077146:Irinotecan; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy; D011073:Polyamines
D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011073:Polyamines; D000077146:Irinotecan; D002166:Camptothecin