2 research outputs found
Enhanced Oral Absorption of Hydrophobic and Hydrophilic Drugs Using Quaternary Ammonium Palmitoyl Glycol Chitosan Nanoparticles
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 <i>P</i> 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 <i>C</i><sub>max</sub> 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 <i>C</i><sub>max</sub> of ranitidine was enhanced by 80% with the
nanomedicine, there was no appreciable opening of tight junctions
by the polymer particles