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

被引:109
作者
Bernardi, A. [1 ]
Zilberstein, A. C. C. V. [2 ]
Jaeger, E. [4 ]
Campos, M. M. [3 ]
Morrone, F. B. [2 ]
Calixto, J. B. [5 ]
Pohlmann, A. R. [6 ]
Guterres, S. S. [4 ]
Battastini, A. M. O. [1 ]
机构
[1] Univ Fed Rio Grande do Sul, ICBS, Dept Bioquim, BR-90035003 Porto Alegre, RS, Brazil
[2] Pontificia Univ Catolica Rio Grande do Sul, Fac Farm, Porto Alegre, RS, Brazil
[3] Pontificia Univ Catolica Rio Grande do Sul, Fac Odontol, Porto Alegre, RS, Brazil
[4] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, BR-90035003 Porto Alegre, RS, Brazil
[5] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Farmacol, Florianopolis, SC, Brazil
[6] Univ Fed Rio Grande do Sul, Inst Quim, Dept Quim Organ, BR-90035003 Porto Alegre, RS, Brazil
关键词
indomethacin; polymeric nanocapsules; drug delivery; inflammation; gastrointestinal damage; NANOPARTICLES; ARTHRITIS; DELIVERY; INHIBITION; CYTOKINES;
D O I
10.1111/j.1476-5381.2009.00244.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 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 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.
引用
收藏
页码:1104 / 1111
页数:8
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