title: Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles.
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.
authors: Department of Pharmaceutics, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors: Adeline
authors: A
authors: Siew
authors: Hang
authors: H
authors: Le
authors: Marion
authors: M
authors: Thiovolet
authors: Paul
authors: P
authors: Gellert
authors: Andreas
authors: A
authors: Schatzlein
authors: Ijeoma
authors: I
authors: Uchegbu
mesh_terms: D000268:Adhesiveness; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D006118:Griseofulvin / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015255:Idarubicin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D011899:Ranitidine / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000897:Anti-Ulcer Agents; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D004337:Drug Carriers; D000644:Quaternary Ammonium Compounds; C114305:palmitoyl glycol chitosan; D006118:Griseofulvin; D016572:Cyclosporine; D011899:Ranitidine; D048271:Chitosan; D015255:Idarubicin