Rohit B Kolhatkar1, Peter Swaan, Hamidreza Ghandehari. 1. Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Baltimore, Maryland, USA.
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.
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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