Preparation, physiochemical characterization, and oral immunogenicity of Aβ(1–12), Aβ(29–40), and Aβ(1–42) loaded PLG microparticles formulations

Abstract

Alzheimer's disease (AD) is caused by the deposition of beta-amyloid (Abeta) protein in brain. The current AD immunotherapy aims to prevent Abeta plaque deposition and enhance its degradation in the brain. In this work, the peptides B-cell epitope Abeta(1-12), T-cell epitope Abeta(29-40) and full-length Abeta(1-42) were loaded separately to the poly (D,L-lactide co-glycolide) (PLG) microparticles by using W/O/W double emulsion solvent evaporation method with entrapment efficacy of 70.46%, 60.93%, and 65.98%, respectively. The prepared Abeta PLG microparticles were smooth, spherical, individual, and nonporous in nature with diameters ranging from 2 to 12 microm. The cumulative in vitro release profiles of Abeta(1-12), Abeta(29-40), and Abeta(1-42) from PLG microparticles sustained for long periods and progressively reached to 73.89%, 69.29%, and 70.08% by week 15. In vitro degradation studies showed that the PLG microparticles maintained the surface integrity up to week 8 and eroded completely by week 16. Oral immunization of Abeta peptides loaded microparticles in mice elicited stronger immune response by inducing anti-Abeta antibodies for prolonged time (24 weeks). The physicochemical characterization and immunogenic potency of Abeta peptides incorporated PLG microparticles suggest that the microparticles formulation of Abeta can be a potential oral AD vaccine.