Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs.
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.
Cattani
Vitória Berg
VB
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.
Fiel
Luana Almeida
LA
Jäger
Alessandro
A
Jäger
Eliézer
E
Colomé
Letícia Marques
LM
Uchoa
Flavia
F
Stefani
Valter
V
Dalla Costa
Teresa
T
Guterres
Sivia Stanisçuaski
SS
Pohlmann
Adriana Raffin
AR
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005456:Fluorescent Dyes; D053769:Nanocapsules; D014014:Tissue Adhesives; C507313:indomethacin ethyl ester; D007213:Indomethacin