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.
Subject(s)
Alzheimer Disease/immunology , Amyloid beta-Peptides/immunology , Delayed-Action Preparations/chemistry , Peptide Fragments/immunology , Polyglactin 910/chemistry , Administration, Oral , Alzheimer Disease/therapy , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , Animals , Antibodies/blood , Delayed-Action Preparations/metabolism , Drug Compounding , Epitopes, B-Lymphocyte/immunology , Epitopes, T-Lymphocyte/immunology , Humans , Immunization , Immunotherapy , Mice , Mice, Inbred BALB C , Particle Size , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Polyglactin 910/metabolism , Random Allocation , Surface PropertiesABSTRACT
Oral hepatitis B vaccine formulation was prepared by successful encapsulation of immunogenic peptide representing residues 127-145 of the immunodominant B-cell epitope of hepatitis B surface antigen (HBsAg) in poly(D,L-lactide co-glycolide) (PLG) microparticles. The smooth, spherical PLG microparticles with a diameter of around 10 microm was prepared by using W/O/W double emulsion solvent evaporation method. The entrapment efficiency of B-cell epitope peptide (BCEP) into PLG microparticles was 64%. In vitro studies showed B-cell epitope loaded PLG microparticles (BCEM) released the peptide in sustained profile and reached 64.9% efficiency by Day 25. Single oral immunization of mice with BCEM led to the significant induction of specific serum IgG and IgM anti-HB antibodies. After the termination of antibody induction, the orally immunized mice were infected with HBsAg, which resulted in the rapid production of antibodies against HBsAg as a result of secondary immune response. PLG microparticles formulation approach may have potential in increasing the efficacy of microparticulate systems for the oral administration of hepatitis B vaccine.
