title: Novel polymer-grafted starch microparticles for mucosal delivery of vaccines.
abstract: Recent studies have demonstrated that systemic and mucosal administration of soluble antigens in biodegradable microparticles can potentiate antigen-specific humoral and cellular immune responses. However, current microparticle formulations are not adequate for all vaccine antigens, necessitating the further development of microparticle carrier systems. In this study, we developed a novel microparticle fabrication technique in which human serum albumin (HSA) was entrapped in starch microparticles grafted with 3-(triethoxysilyl)-propyl-terminated polydimethylsiloxane (TS-PDMS), a biocompatible silicone polymer. The immunogenicity of HSA was preserved during the microparticle fabrication process. Following intraperitoneal immunization of mice, TS-PDMS-grafted microparticles (MP) dramatically enhanced serum IgG responses compared with ungrafted MP and soluble HSA alone (P < 0.001). When delivered orally, both TS-PDMS-grafted and ungrafted microparticles elicited HSA-specific IgA responses in gut secretions, in contrast to orally administered soluble antigen. Indeed, TS-PDMS-grafted microparticles stimulated significantly stronger serum IgG (P < 0.005) and IgA (P < 0.001) responses compared with those elicited by ungrafted microparticles. These findings indicate that TS-PDMS-grafted starch microparticles have potential as systemic and mucosal vaccine delivery vehicles.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: P L
authors.initials: PL
authors.lastname: Heritage
authors.forename: L M
authors.initials: LM
authors.lastname: Loomes
authors.forename: J
authors.initials: J
authors.lastname: Jianxiong
authors.forename: M A
authors.initials: MA
authors.lastname: Brook
authors.forename: B J
authors.initials: BJ
authors.lastname: Underdown
authors.forename: M R
authors.initials: MR
authors.lastname: McDermott
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001673:Biodegradation, Environmental; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D012709:Serum Albumin / Q000008:administration & dosage* / Q000276:immunology; D012828:Silicones; D013213:Starch
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012709:Serum Albumin; D012828:Silicones; D013213:Starch