title: Efficient delivery of the toll-like receptor agonists polyinosinic:polycytidylic acid and CpG to macrophages by acetalated dextran microparticles.
abstract: To enhance the immune activity of vaccine adjuvants polyinosinic:polycytidylic acid (poly I:C) and CpG acetalated dextran (Ac-DEX) microparticles can be used. Ac-DEX is a biodegradable and water-insoluble polymer that degrades significantly faster at pH 5.0 (phagosomal pH) than at pH 7.4 and has tunable degradation rates that can range from hours to months. This is an ideal characteristic for delivery of an antigen and adjuvant within the lysosomal compartment of a phagocytic cell. We evaluated poly I:C and CpG encapsulated in Ac-DEX microparticles using RAW macrophages as a model antigen-presenting cell. These cells were cultured with poly I:C or CpG in their free form, encapsulated in a fast degrading Ac-DEX, in slow degrading Ac-DEX, or in the Food and Drug Administration-approved polymer poly(lactic-co-glycolic acid) (PLGA). Ac-DEX had higher encapsulation efficiencies for both poly I:C and CpG than PLGA. Furthermore, poly I:C or CpG encapsulated in Ac-DEX also showed, in general, a significantly stronger immunostimulatory response than PLGA and unencapsulated CpG or poly I:C, which was indicated by a higher rate of nitric oxide release and increased levels of cytokines such as TNF-α, IL-6, IL-10, and IFN-γ. Overall, we have illustrated a method for enhancing the delivery of these vaccine adjuvants to further enhance the development of Ac-DEX vaccine formulations.
authors.affiliation: Molecular, Cellular and Developmental Biology Graduate Program, ‡Division of Pharmaceutics, College of Pharmacy, §College of Veterinary Medicine, and ∥William G. Lowrie Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Peine
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.forename: Zachary
authors.initials: Z
authors.lastname: Vangundy
authors.forename: Tracy
authors.initials: T
authors.lastname: Papenfuss
authors.forename: Deanna J
authors.initials: DJ
authors.lastname: Brackman
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Gallovic
authors.forename: Kevin
authors.initials: K
authors.lastname: Schully
authors.forename: John
authors.initials: J
authors.lastname: Pesce
authors.forename: Andrea
authors.initials: A
authors.lastname: Keane-Myers
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D000818:Animals; D002460:Cell Line; D003911:Dextrans / Q000737:chemistry; D015226:Dinucleoside Phosphates / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018625:Microscopy, Atomic Force; D011070:Poly I-C / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D003911:Dextrans; D015226:Dinucleoside Phosphates; D011070:Poly I-C; D051193:Toll-Like Receptors; C015772:CpG dinucleotide