Potential oral delivery of 7-ethyl-10-hydroxy-camptothecin (SN-38) using poly(amidoamine) dendrimers

Pharm Res. 2008 Jul;25(7):1723-9. doi: 10.1007/s11095-008-9572-9. Epub 2008 Apr 26.

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