Preparation, Physiochemical Characterization, and Oral Immunogenicity of A beta(1-12), A beta(29-40), and A beta(1-42) Loaded PLG Microparticles Formulations

作者：Rajkannan R; Arul V; Malar E J Padma; Jayakumar R^*

来源：Journal of Pharmaceutical Sciences, 2009, 98(6): 2027-2039.

DOI：10.1002/jps.21600

• oral AD vaccine
• A beta PLG microparticles oral vaccine
• B-cell epitope A beta(1-12)
• T-cell epitope A beta(29-40)
• Anti-A beta antibodies
• mucosal immunization
• peptide delivery
• vaccine adjuvants
• biodegradable polymers
• microparticles

Alzheimer's disease (AD) is caused by the deposition of beta-anlyloid (A beta) protein in brain. The current AD immunotherapy aims to prevent A beta plaque deposition and enhance its degradation in the brain. In this work, the peptides B-cell epitope A beta(1-12), T-cell epitope A beta(29-40) and full-length A beta(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 A beta PLG microparticles were smooth, spherical, individual, and nonporous in nature with diameters ranging from 2 to 12 mu m. The cumulative in vitro release profiles of A beta(1-12), A beta(29-40), and A beta(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 A beta peptides loaded microparticles in mice elicited stronger immune response by inducing anti-A beta antibodies for prolonged time (24 weeks). The physicochemical characterization and immunogenic potency of A beta peptides incorporated PLG microparticles suggest that the microparticles formulation of A beta can be a potential oral AD vaccine.

• 出版日期2009-6