Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles.

TitleEnhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles.
Publication TypeJournal Article
Year of Publication2012
AuthorsSiew A, Le H, Thiovolet M, Gellert P, Schätzlein A, Uchegbu I
JournalMol Pharm
Volume9
Issue1
Pagination14-28
Date Published2012 Jan 1
ISSN1543-8392
KeywordsAdhesiveness, Animals, Anti-Ulcer Agents, Antibiotics, Antineoplastic, Antifungal Agents, Caco-2 Cells, Chitosan, Cyclosporine, Drug Carriers, Griseofulvin, Humans, Hydrophobic and Hydrophilic Interactions, Idarubicin, Intestinal Absorption, Intestinal Mucosa, Intestine, Small, Male, Nanoparticles, Quaternary Ammonium Compounds, Ranitidine, Rats, Rats, Wistar
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.

DOI10.1021/mp200469a
Alternate JournalMol. Pharm.
PubMed ID22047066