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Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers

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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.

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Acknowledgments

The authors appreciate the efforts of Dr. Kelly Hom for assisting with NMR studies. Financial support was provided by the Department of Defense multidisciplinary postdoctoral fellowship award (W81XWH-06-1-0698) to Rohit Kolhatkar, a University System of Maryland Integrated Nanobio seed grant through the Maryland Department of Business and Economic Development and NIH R01EB07470.

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Author notes

  1. Hamidreza Ghandehari

    Present address: Departments of Pharmaceutics and Pharmaceutical Chemistry and Bioengineering, University of Utah, 383 Colorow Road, Room 343, Salt Lake City, Utah, 84108, USA

Authors and Affiliations

  1. Center for Nanomedicine and Cellular Delivery, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Baltimore, Maryland, USA

    Rohit B. Kolhatkar, Peter Swaan & Hamidreza Ghandehari

Authors
  1. Rohit B. Kolhatkar
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  2. Peter Swaan
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  3. Hamidreza Ghandehari
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Correspondence to Hamidreza Ghandehari.

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Kolhatkar, R.B., Swaan, P. & Ghandehari, H. Potential Oral Delivery of 7-Ethyl-10-Hydroxy-Camptothecin (SN-38) using Poly(amidoamine) Dendrimers. Pharm Res 25, 1723–1729 (2008). https://doi.org/10.1007/s11095-008-9572-9

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  • DOI: https://doi.org/10.1007/s11095-008-9572-9

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