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 ± 4% inhibition) and the arthritis (35 ± 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 ± 2% and 14 ± 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 α and IL‐6 (by 83 ± 8% and 84 ± 11% respectively), while the levels of the anti‐inflammatory cytokine IL‐10 were significantly increased (196 ± 55%). The indices of gastrointestinal damage in IndOH‐NC‐treated animals were significantly less that those after IndOH treatment (58 ± 16%, 72 ± 6% and 69 ± 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.

This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009