Protective effect of meloxicam-loaded nanocapsules against amyloid-β peptide-induced damage in mice

The objective of present study was to investigate the protective effect of M-NC against a beta (25-35) peptide-induced damage in mice, as the first step to evaluate their potential value for the treatment of AD. Moreover, we compared the effects of M-NC with free meloxicam (M-F). Mice were divided into six groups: (I) sham, (II) a beta, (III) M-NC, (IV) M-F, (V) M-NC + a beta and (VI) M-F + a beta. Mice were pre-treated with M-NC (5 mg/kg, by gavage), M-F (5 mg/kg, by gavage) or blank nanocapsules (B-NC). Thirty minutes after treatments, a beta peptide (3 nmol) or filtered water were icy, injected. Learning and memory were assessed with the Morris water maze (MWM) (days 4-7) and step-down-type passive-avoidance (SDPA) (days 7-8) tasks. At the end of the experimental protocol (day 8), animals were euthanized and brains were removed for biochemical determinations (reactive species (RS), non-protein thiols (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST)) and histological examination. Our results confirmed that a beta peptide caused learning and memory deficits in mice. Histological analysis demonstrated neuronal loss, intense cellular accumulation and chromatolysis caused by a beta peptide. Furthermore, this study showed that oxidative stress was increased in mice that received a beta peptide. An important finding of the present study was the protective effect of M-NC in damage induced by a beta peptide. However, M-F did not have protective effect. In summary, the data reported herein clearly demonstrate that meloxicam carried by polymeric nanocapsules protected against learning and memory impairments, loss neuronal and oxidative stress in a mouse model of AD induced by a beta peptide. (C) 2012 Elsevier B.V. All rights reserved.