title: Chemically modified inulin microparticles serving dual function as a protein antigen delivery vehicle and immunostimulatory adjuvant.
abstract: To develop a new subunit vaccine adjuvant, we chemically modified a naturally-occurring, immunostimulatory inulin polysaccharide to produce an acid-sensitive biopolymer (acetalated inulin, Ace-IN). Various hydrophobic Ace-IN polymers were formed into microparticles (MPs) by oil-in-water emulsions followed by solvent evaporation These Ace-IN MPs possessed tunable degradation characteristics that, unlike polyesters used in FDA-approved microparticulate formulations, had only pH-neutral hydrolytic byproducts. Macrophages were passively targeted with cytocompatible Ace-IN MPs. TNF-α production by macrophages treated with Ace-IN MPs could be altered by adjusting the polymers' chemistry. Mice immunized with Ace-IN MPs encapsulating a model ovalbumin (OVA) antigen showed higher production of anti-OVA IgG antibody levels relative to soluble antigen. The antibody titers were also comparable to an alum-based formulation. This proof-of-concept establishes the potential for chemically-modified inulin MPs to simultaneously enable dual functionality as a stimuli-controlled antigen delivery vehicle and immunostimulatory adjuvant.
authors.affiliation: Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Gallovic
authors.affiliation: Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Montjoy
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. ainsliek@email.unc.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Collier
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Clement
authors.initials: C
authors.lastname: Do
authors.affiliation: Department of Chemical and Biomolecular Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA and Department of Chemistry and Biochemistry, College of Arts and Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Wyslouzil
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. ainsliek@email.unc.edu.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. ainsliek@email.unc.edu.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Ainslie
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic; D000818:Animals; D000941:Antigens / Q000737:chemistry* / Q000276:immunology; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D006863:Hydrogen-Ion Concentration; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007444:Inulin / Q000138:chemical synthesis* / Q000737:chemistry; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry*; D011134:Polysaccharides / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D000277:Adjuvants, Pharmaceutic; D000941:Antigens; D005079:Excipients; D007074:Immunoglobulin G; D011134:Polysaccharides; D007444:Inulin; D010047:Ovalbumin