title: Effectiveness of submicronized chitosan-coated liposomes in oral absorption of indomethacin.
abstract: The plasma profile of indomethacin (IMC) after oral administration of IMC-loaded submicronized chitosan-coated liposomes (ssCS-Lip) was evaluated to reveal the effectiveness of the mucoadhesive function for improving the absorption of this poorly absorbable drug. The stomach and small intestine were removed from rats after 1, 2, and 4 hours of oral administration of submicron-sized liposomes (ssLip) or ssCS-Lip containing fluorescent dye, and the retentive properties were confirmed by measuring the amount of dye in each part of the gastrointestinal (GI) tract. Results showed that ssCS-Lip tended to be better retained in the upper part of the GI tract, compared with ssLip, at 1, 2, and 4 hours after administration, and was significantly better retained in the small intestine at 4 hours. The plasma profile and bioavailability of IMC after oral administration of both types of liposomes were improved, compared with oral administration of IMC solution. The maximum residence time of ssCS-Lip was significantly longer than those of ssLip. The extended plasma profile of ssCS-Lip was attributed to its prolonged retention in the upper region of the GI tract, and its delayed migration to the lower part of the intestine, the neutral pH of which is more soluble for IMC, an acidic drug. Therefore, the chitosan-coated ssLip, with its higher retention in the GI tract, is a promising drug carrier for the oral administration of poorly absorbed compounds.
authors.affiliation: Gifu Pharmaceutical University, Laboratory of Pharmaceutical Engineering, Department of Drug Delivery Technology and Sciences, Gifu, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugihara
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000097:blood / Q000737:chemistry*; D007213:Indomethacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008081:Liposomes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D013997:Time Factors
chemical_list: D008081:Liposomes; D048271:Chitosan; D007213:Indomethacin