Indomethacin-loaded poly ( d,l-lactide) nanocapsules protection from gastrointestinal ulcerations and anti-inflammatory activity evaluation in rats

Abstract

Indomethacin-loaded nanocapsules were prepared by deposition of poly ( d,l-lactide) polymer (PLA) at the oil/water interface following acetone displacement from the oily nanodroplets. Rapid in-vitro release profiles of indomethacin from PLA nanocapsules were observed at pH above 7·0 Nanoencapsulation of indomethacin induced a marked protective effect on the gastro-intestinal tissues as compared to the ulcerative effect observed with the aqueous solution of the drug following three consecutive oral daily doses of 10 mg/kg. It was shown that the induced protective effect displayed by the PLA nanocapsules was rather associated with low tissue concentration than with high plasma concentration. The incorporation of indomethacin in the PLA nanocapsules did not alter the pharmacological activity of the drug, since similar edema inhibition profiles were observed for the aqueous solution and for the PLA nanocapsules using the carrageenininduced edema test in the hind paw of rats. Furthermore, the anti-inflammatory activity of indomethacin was enhanced following incorporation in the PLA nanocapsules. Two possible explanations were proposed for the overall result interpretations.