Meloxicam-loaded nanocapsules as an alternative to improve memory decline in an Alzheimer's disease model in mice: involvement of Na(+), K(+)-ATPase

Metab Brain Dis. 2016 Aug;31(4):793-802. doi: 10.1007/s11011-016-9812-3. Epub 2016 Feb 27.

Abstract

The objective of this study was to investigate the effect of meloxicam-loaded nanocapsules (M-NC) on the treatment of the memory impairment induced by amyloid β-peptide (aβ) in mice. The involvement of Na(+), K(+)-ATPase and cyclooxygenase-2 (COX-2) activities in the hippocampus and cerebral cortex was also evaluated. Mice received aβ (3 nmol/ 3 μl/ per site, intracerebroventricular) or vehicle (3 μl/ per site, i.c.v.). The next day, the animals were treated with blank nanocapsules (17 mL/kg) or M-NC (5 mg/kg) or free meloxicam (M-F) (5 mg/kg). Treatments were performed every other day, until the twelfth day. Animals were submitted to the behavioral tasks (open-field, object recognition, Y-maze and step-down inhibitory avoidance tasks) from the twelfth day. Na(+), K(+)-ATPase and COX-2 activities were performed in hippocampus and cerebral cortex. aβ caused a memory deficit, an inhibition of the hippocampal Na(+), K(+)-ATPase activity and an increase in the hippocampal COX-2 activity. M-NC were effective against all behavioral and biochemical alterations, while M-F restored only the COX-2 activity. In conclusion, M-NC were able to reverse the memory impairment induced by aβ, and Na(+), K(+)-ATPase is involved in the effect of M-NC.

Keywords: Amyloid-β; Cyclooxygenase; Drug-delivery; Meloxicam; Nanoparticles.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Meloxicam
  • Memory / drug effects
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Mice
  • Nanocapsules / administration & dosage*
  • Sodium-Potassium-Exchanging ATPase / metabolism*
  • Thiazines / administration & dosage
  • Thiazines / therapeutic use*
  • Thiazoles / administration & dosage
  • Thiazoles / therapeutic use*

Substances

  • Nanocapsules
  • Thiazines
  • Thiazoles
  • Cyclooxygenase 2
  • Sodium-Potassium-Exchanging ATPase
  • Meloxicam