title: Vaccine-like controlled-release delivery of an immunomodulating peptide to treat experimental autoimmune encephalomyelitis.
abstract: The objective of this work is to use colloidal gel from alginate-chitosan-PLGA complex to deliver Ac-PLP-BPI-NH₂-2 peptide in a controlled-release manner as a vaccine-like therapeutic to suppress experimental autoimmune encephalomyelitis (EAE) in the mouse model. Oppositely charged PLGA nanoparticles were prepared by a solvent diffusion method. The carboxyl group of the alginate and the amine group of the chitosan coated the nanoparticles with negative and positive charges, respectively. The peptide (Ac-PLP-BPI-NH₂-2), designed to bind to MHC-II and ICAM-1 simultaneously, was formulated into the colloidal gel by physical mixture. Vaccine-like administration of the peptide-loaded colloidal gel (Ac-PLP-BPI-NH₂-2-NP) was achieved by subcutaneous (sc) injection to EAE mice. Disease severity was measured using clinical scoring and percent change in body weight. Cytokine production was determined using the splenocytes from Ac-PLP-BPI-NH₂-2-NP-treated mice and compared to that of controls. Ac-PLP-BPI-NH₂-2-NP suppressed and delayed the onset of EAE as well as Ac-PLP-BPI-NH₂-2 when delivered in a vaccine-like manner. IL-6 and IL-17 levels were significantly lower in the Ac-PLP-BPI-NH₂-2-NP-treated mice compared to the mouse group treated with blank colloidal gel, suggesting that the mechanism of suppression of EAE is due to a shift in the immune response away from Th17 production. The results of this study suggest that a one-time sc administration of Ac-PLP-BPI-NH₂-2 formulated in a colloidal gel can produce long-term suppression of EAE by reducing Th17 proliferation.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas , Lawrence, Kansas, USA.
authors.forename: Barlas
authors.initials: B
authors.lastname: Büyüktimkin
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Kiptoo
authors.forename: John M
authors.initials: JM
authors.lastname: Stewart
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D007155:Immunologic Factors / Q000627:therapeutic use*; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D010455:Peptides / Q000627:therapeutic use*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D007155:Immunologic Factors; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid