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

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• 作者：Adeline Siew ; Hang Le ; Marion Thiovolet ; Paul Gellert ; Andreas Schatzlein ; Ijeoma Uchegbu
• 刊名：Molecular Pharmaceutics
• 出版年：2012
• 出版时间：January 1, 2012
• 年：2012
• 卷：9
• 期：1
• 页码：14-28
• 全文大小：620K
• 年卷期：v.9,no.1(January 1, 2012)
• ISSN：1543-8392

文摘

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.

Keywords:

oral absorption; chitosan amphiphiles; hydrophobic drugs; hydrophilic drugs; mucoadhesion; transcellular transport; griseofulvin; cyclosporin A; idarubicin; ranitidine