Journal
PHARMACEUTICAL RESEARCH
Volume 25, Issue 7, Pages 1723-1729Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-008-9572-9
Keywords
camptothecin; oral drug delivery; PAMAM dendrimer; SN-38
Funding
- NIBIB NIH HHS [R01 EB007470-02, R01 EB007470-01A2, R01 EB007470-03, R01EB07470, R01 EB007470] Funding Source: Medline
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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.
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