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

Alzheimer's disease (AD) is caused by the deposition of β-amyloid (Aβ) protein in brain. The current AD immunotherapy aims to prevent Aβ plaque deposition and enhance its degradation in the brain. In this work, the peptides B-cell epitope Aβ(1–12), T-cell epitope Aβ(29–40) and full-length Aβ(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 Aβ PLG microparticles were smooth, spherical, individual, and nonporous in nature with diameters ranging from 2 to 12 µm. The cumulative in vitro release profiles of Aβ(1–12), Aβ(29–40), and Aβ(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 Aβ peptides loaded microparticles in mice elicited stronger immune response by inducing anti-Aβ antibodies for prolonged time (24weeks). The physicochemical characterization and immunogenic potency of Aβ peptides incorporated PLG microparticles suggest that the microparticles formulation of Aβ can be a potential oral AD vaccine. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2027–2039, 2009