Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-β-cyclodextrin on β-Amyloid (1-42)–Induced Toxicity

Abstract

β-Amyloid (Aβ) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and Aβ aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after Aβ(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. Aβ(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against Aβ(1-42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against Aβ(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spray-dried HP-CD microspheres are able to provide protection against Aβ(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus.