title: Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs.
abstract: The aim of this work was to investigate if the indomethacin ethyl ester (IndOEt) released from lipid-core nanocapsules (NC) is converted into indomethacin (IndOH) in the intestine lumen, intestine wall or after the particles reach the blood stream. NC-IndOEt had monomodal size distribution (242 nm; PDI 0.2) and zeta potential of -11 mV. The everted rat gut sac model showed IndOEt passage of 0.16 micromol m(-2) through the serosal fluid (30 min). From 15 to 120 min, the IndOEt concentrations in the tissue increased from 6.13 to 27.47 micromol m(-2). No IndOH was formed ex vivo. A fluorescent-NC formulation was used to determine the copolymer bioadhesion (0.012 micromol m(-2)). After NC-IndOEt oral administration to rats, IndOEt and IndOH were detected in the gastrointestinal tract (contents and tissues). In the tissues, the IndOEt concentrations decreased from 459 to 5 microg g(-1) after scrapping, demonstrating the NC mucoadhesion. In plasma (peripheric and portal vein), in spleen and liver, exclusively IndOH was detected. In conclusion, after oral dosing of NC-IndOEt, IndOEt is converted into IndOH in the intestinal lumen and wall before reaching the blood stream. The complexity of a living system was not predicted by the ex vivo gut sac model.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Vitória Berg
authors.initials: VB
authors.lastname: Cattani
authors.forename: Luana Almeida
authors.initials: LA
authors.lastname: Fiel
authors.forename: Alessandro
authors.initials: A
authors.lastname: Jäger
authors.forename: Eliézer
authors.initials: E
authors.lastname: Jäger
authors.forename: Letícia Marques
authors.initials: LM
authors.lastname: Colomé
authors.forename: Flavia
authors.initials: F
authors.lastname: Uchoa
authors.forename: Valter
authors.initials: V
authors.lastname: Stefani
authors.forename: Teresa
authors.initials: T
authors.lastname: Dalla Costa
authors.forename: Sivia Stanisçuaski
authors.initials: SS
authors.lastname: Guterres
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006868:Hydrolysis; D007213:Indomethacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D014014:Tissue Adhesives / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005456:Fluorescent Dyes; D053769:Nanocapsules; D014014:Tissue Adhesives; C507313:indomethacin ethyl ester; D007213:Indomethacin