Abstract
Purpose:
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Antineoplastic Agents, Phytogenic / administration & dosage*
-
Antineoplastic Agents, Phytogenic / pharmacokinetics
-
Antineoplastic Agents, Phytogenic / pharmacology
-
Caco-2 Cells
-
Camptothecin / administration & dosage
-
Camptothecin / analogs & derivatives*
-
Camptothecin / pharmacokinetics
-
Camptothecin / pharmacology
-
Cell Survival / drug effects
-
Chemical Phenomena
-
Chemistry, Physical
-
Dendrimers
-
Drug Carriers
-
Drug Delivery Systems
-
Epithelium / metabolism
-
Humans
-
Injections, Intravenous
-
Irinotecan
-
Isotope Labeling
-
Magnetic Resonance Spectroscopy
-
Polyamines
Substances
-
Antineoplastic Agents, Phytogenic
-
Dendrimers
-
Drug Carriers
-
PAMAM Starburst
-
Polyamines
-
Irinotecan
-
Camptothecin