Encapsulation of indomethacin in liposomes provides protection against both gastric and intestinal ulceration when orally administered to rats

Abstract

Encapsulation of indomethacin into egg phosphatidylcholine (EPC) monophasic vesicles (MPV) or into stable plurilamellar vesicles (SPLV) before oral administration to rats substantially reduced or eliminated the gastric and intestinal ulceration normally associated with ingestion of this drug. Ulcers were assessed by the 4-hour single-dose gastric ulceration model and the 4-or 14-day repeated-dose intestinal ulceration model, using microscopic/planimetric quantitation. Oral dosages of up to 10 mg/kg of indomethacin in polyethylene glycol400 resulted in substantial gastric ulceration, but not when given in methylcellulose suspension or as EPCMPV. Severe intestinal ulcers resulted following oral administration of indomethacin in either vehicle at daily 3-4-mg/kg doses, but did not result from EPCMPV formulations, whether dosed for 4 days or 14 days. Oral administration of pH-sensitive indomethacin liposomes constructed from cholesterol hemisuccinate resulted in loss of the protective action. Indomethacin-MPV showed both comparable bioactivity and comparable blood levels of the drug when contrasted with free drug in vehicles. Biodistribution studies demonstrated that when delivered from liposomes, drug and phospholipid are rapidly cleared through the stomach but then are differentially absorbed. Empty EPCMPV given by

Mechanical properties of polycarbonate/modified acrylonitrile‐styrene‐acrylate terpolymer blend

“…In this case the number of hemorrhage point, the number of ulceration and average trauma degree was 16.12 ± 2.93, 2.75 ± 1.39 and 3.25 ± 0.43 respectively, while the corresponding values were significantly lower for micelles treated groups at doses of 0.5 mg kg −1 (0, 0, and 0), 1.5 mg kg −1 (0.25 ± 0.43, 0 and 0.25 ± 0.43), and 4.5 mg kg −1 (0.50 ± 0.71, 0 and 0.38 ± 0.48). This result further suggests that intra‐articular injection of IND‐loaded micelles could alleviate the significant gastrointestinal stimulation that frequently observed for oral administration and subcutaneous injection in abdomen as well, as reported by Soehngen et al45…”

Physicochemical characterization, in vitro, and in vivo evaluation of indomethacin‐loaded nanocarriers self‐assembled by amphiphilic polyphosphazene

“…In this case the number of hemorrhage point, the number of ulceration and average trauma degree was 16.12 6 2.93, 2.75 6 1.39 and 3.25 6 0.43 respectively, while the corresponding values were significantly lower for micelles treated groups at doses of 0.5 mg kg À1 (0, 0, and 0), 1.5 mg kg À1 (0.25 6 0.43, 0 and 0.25 6 0.43), and 4.5 mg kg À1 (0.50 6 0.71, 0 and 0.38 6 0.48). This result further suggests that intra-articular injection of IND-loaded micelles could alleviate the significant gastrointestinal stimulation that frequently observed for oral administration and subcutaneous injection in abdomen as well, as reported by Soehngen et al 45 Additionally, in combination with our previous result based on polyphosphazenes with PNIPAAm and ethyl tryptophan (EtTrp) as substitutes, 26 we can conclude that the hydrophobic group has no significant effect on the in vivo therapeutic efficacy. However, detailed in vivo evaluation still needs to be carried out to address the effect of copolymer composition on the local tissue reaction, such as stimulation, inflammation, toxicity, and so forth.…”

Phospholipids and Lipid-Based Formulations in Oral Drug Delivery

“…Various publications also show for orally administered indomethacin in a DPPC/ tripalmitine microemulsion (53) or indomethacin in liposomes (EPC/ DPPC; Soehngen (89)) that the use of phospholipids reduces the gastrointestinal side effects.…”