Background and purpose:The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. Experimental approach: The following models of inflammation were employed: carrageenan-induced acute oedema (measured between 30 min and 4 h), sub-chronic oedema induced by complete Freund's adjuvant (CFA) (determined between 2 h and 72 h), and CFA-induced arthritis (oedema measured between 14 and 21 days). Key results: IndOH or IndOH-NC produced equal inhibition of carrageenan-elicited oedema. However, IndOH-NC was more effective in both the sub-chronic (33 Ϯ 4% inhibition) and the arthritis (35 Ϯ 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 Ϯ 2% and 14 Ϯ 3% inhibition respectively) (P < 0.01). In the CFA arthritis model, treatment with IndOH-NC markedly inhibited the serum levels of the pro-inflammatory cytokines tumour necrosis factor a and IL-6 (by 83 Ϯ 8% and 84 Ϯ 11% respectively), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased (196 Ϯ 55%). The indices of gastrointestinal damage in IndOH-NC-treated animals were significantly less that those after IndOH treatment (58 Ϯ 16%, 72 Ϯ 6% and 69 Ϯ 2%, for duodenum, jejunum and ileum respectively). Conclusions and implications: IndOH-NC produced an increased anti-inflammatory efficacy in long-term models of inflammation, allied to an improved gastrointestinal safety. This formulation might represent a promising alternative for treating chronic inflammatory diseases, with reduced undesirable effects.
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