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

Abstract

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.

Indomethacin-loaded lipid-core nanocapsules reduce the damage triggered by A&beta;1-42 in Alzheimer&rsquo;s disease models

“…This method of drug delivery has been shown to decrease gastrointestinal side effects and increase the brain biodistribution of IndOH. 19,46 In the present study, we reported that by using LNCs, even low concentrations of IndOH (such as 50 µM) were able to protect against cell death induced by Aβ1-42 exposure in organotypic culture. Possible mechanisms underlying the similar effects observed with both concentrations of IndOH-LNCs in the present study may include the NC uptake endocytosis by the cells achieved through endocytosis.…”

“…Our previous work has shown that this formulation increased the levels of IL-10 in peripheral inflammation models. 46 Here, we noticed that treatment with IndOH-LNCs increased levels of IL-10 in the presence or absence of Aβ. In this way, our data demonstrate that IndOH was able to break the inflammatory response induced by Aβ, culminating in the protective effect on cell death, as observed by PI incorporation.…”

“…Our previous work has shown that treatment of rats with the same dose of IndOH-LNCs used in the present study induced a marked protective effect on the gastrointestinal mucosa compared with the ulcerative effect observed with the treatment with IndOH. 46 Additionally, neither free nor nanoencapsulated IndOH, altered hepatic function or hematological parameters in our experimental conditions. Development of combined treatments using compounds with different bioavailability, pharmacokinetics, and metabolism is challenging.…”

Development of noncytotoxic PLGA nanoparticles to improve the effect of a new inhibitor of p53–MDM2 interaction

“…Nanocapsules containing compound 1 were prepared by the SD previously described method (Bernardi et al, 2009;Zili et al, 2005), as described in Table 1 (formulations VII-VIII). Concisely, an acetonic solution of PLGA containing or not the lipophilic surfactant Span ® 80 was prepared.…”

Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in&nbsp;synovial cells and a chronic arthritis model

“…The capacity of the LNC to increase the drug's action on the reduction of proinflammatory cytokines has also been demonstrated in a rat arthritis model, in which LNC that contained indomethacin (IndOH-LNC) reduced cytokines; however, there was no significant effect for the drug in solution. 43 Finally, resistance to MTX is another current issue in the treatment of RA because it compromises clinical responsiveness to the drug. Resistance to MTX occurs because of a wide range of mechanisms, including MTX uptake by a reduced folate carrier, an increase of MTX efflux, a decrease of MTX polyglutamation, and an overexpression of dihydrofolate reductase.…”