Encapsulation of Aβ(1-15) in PLGA microparticles enhances serum antibody response in mice immunized by subcutaneous and intranasal routes

Eur J Pharm Sci. 2011 Oct 9;44(3):200-6. doi: 10.1016/j.ejps.2011.07.010. Epub 2011 Jul 27.

Abstract

The aim of the present work was to develop an easy, safe and effective vaccine in Balb/c mice using the Aβ(1-15) peptide as immunogen entrapped in PLGA microparticles to reduce the risk of an adverse T cell-mediated response. Aβ(1-15,) which contains the N-terminal antibody epitope of the full Aβ(1-42) peptide was encapsulated in PLGA by a modified solvent evaporation/extraction technique using a double emulsion system. Microparticles were characterized in terms of size distribution (1.22±0.28 μm), encapsulation efficiency (75.05±4.17%), surface associated peptide (59.81±0.96%) and "in vitro" release profile. Balb/c mice were immunized by subcutaneous and intranasal routes with three 30 μg doses of the peptide microencapsulated in PLGA. A solution of the peptide alone and an emulsion in the Freund's adjuvant were administered subcutaneously as control groups. Antibody levels elicited against the toxic Aβ(1-40) fraction in the serum of PLGA microparticles treated groups were higher than that of the peptide alone groups. Our initial results indicate that immunotherapy with Aβ(1-15) loaded PLGA microparticles could be a promising approach for the future development of a safe vaccine against Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Alzheimer Disease / immunology
  • Alzheimer Disease / therapy*
  • Alzheimer Vaccines / administration & dosage
  • Alzheimer Vaccines / immunology*
  • Alzheimer Vaccines / therapeutic use
  • Amyloid beta-Peptides / administration & dosage
  • Amyloid beta-Peptides / immunology*
  • Amyloid beta-Peptides / therapeutic use
  • Animals
  • Drug Administration Schedule
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, B-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Immunoglobulin G / blood*
  • Injections, Subcutaneous
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Particle Size
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology*
  • Peptide Fragments / therapeutic use
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Surface Properties

Substances

  • Alzheimer Vaccines
  • Amyloid beta-Peptides
  • Drug Carriers
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Immunoglobulin G
  • Peptide Fragments
  • amyloid beta-protein (1-15)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid