Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats.
OBJECTIVE
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.


METHODS
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).


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 alpha 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
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.
Bernardi
A
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Zilberstein
A C C V
AC
Jäger
E
E
Campos
M M
MM
Morrone
F B
FB
Calixto
J B
JB
Pohlmann
A R
AR
Guterres
S S
SS
Battastini
A M O
AM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D053769:Nanocapsules / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000893:Anti-Inflammatory Agents; D053769:Nanocapsules; D007213:Indomethacin