Preparation, physiochemical characterization, and oral immunogenicity of Abeta(1-12), Abeta(29-40), and Abeta(1-42) loaded PLG microparticles formulations.
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.
Rajkannan
R
R
Bioorganic and Neurochemistry Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, Tamil Nadu, India.
Arul
V
V
Malar
E J Padma
EJ
Jayakumar
R
R
D000284:Administration, Oral; D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000097:blood; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007114:Immunization; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011098:Polyglactin 910 / Q000737:chemistry* / Q000378:metabolism; D011897:Random Allocation; D013499:Surface Properties
D016229:Amyloid beta-Peptides; D000906:Antibodies; D003692:Delayed-Action Preparations; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; C542321:amyloid beta-protein (1-12); C075222:amyloid beta-protein (1-42); C419409:amyloid beta-protein (29-40); D011098:Polyglactin 910