Enhanced Oral Absorption of Hydrophobic and Hydrophilic Drugs Using Quaternary Ammonium Palmitoyl Glycol Chitosan Nanoparticles

Siew, A., Leake, H., Thiovolet, M., Gellert, P., Schatzlein, A.G. and Uchegbu, I.F. (2012) Enhanced Oral Absorption of Hydrophobic and Hydrophilic Drugs Using Quaternary Ammonium Palmitoyl Glycol Chitosan Nanoparticles. Molecular Pharmaceutics, 9 (1). pp. 14-28. 10.1021/mp200469a.

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DOI: 10.1021/mp200469a

Abstract

As 95% of all prescriptions are for orally administered drugs, the issue of oral absorption is central to the development of pharmaceuticals. Oral absorption is limited by a high molecular weight (>500 Da), a high log P value (>2.0) and low gastrointestinal permeability. We have designed a triple action nanomedicine from a chitosan amphiphile: quaternary ammonium palmitoyl glycol chitosan (GCPQ), which significantly enhances the oral absorption of hydrophobic drugs (e.g., griseofulvin and cyclosporin A) and, to a lesser extent, the absorption of hydrophilic drugs (e.g., ranitidine). The griseofulvin and cyclosporin A C max was increased 6- and 5-fold respectively with this new nanomedicine. Hydrophobic drug absorption is facilitated by the nanomedicine: (a) increasing the dissolution rate of hydrophobic molecules, (b) adhering to and penetrating the mucus layer and thus enabling intimate contact between the drug and the gastrointestinal epithelium absorptive cells, and (c) enhancing the transcellular transport of hydrophobic compounds. Although the C max of ranitidine was enhanced by 80% with the nanomedicine, there was no appreciable opening of tight junctions by the polymer particles.

Item Type:Article
Uncontrolled Keywords:chitosan amphiphiles; cyclosporin A; griseofulvin; hydrophilic drugs; hydrophobic drugs; idarubicin; mucoadhesion; oral absorption; ranitidine; transcellular transport
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2795
Journal or Publication Title:Molecular Pharmaceutics
Deposited By:Library Staff
Deposited On:10 Feb 2012 11:05
Last Modified:24 Feb 2012 17:25

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