title: Chitosan hydrogels containing liposomes and cubosomes as particulate sustained release vaccine delivery systems.
abstract: Sustained release depot systems have been widely investigated for their potential to improve the efficacy of subunit vaccines and reduce the requirement for boosting. The present study aimed to further enhance the immunogenicity of a sustained release vaccine by combining a depot formulation with a particulate antigen delivery system. Sustained release of the model subunit antigen, ovalbumin (OVA), was observed in vivo from chitosan thermogel-based formulations containing cationic, nanosized liposomes loaded with OVA and the immunopotentiator, Quil A (QA). Such formulations demonstrated the ability to induce cluster of differentiation (CD)8(+) and CD4(+) T-cell proliferation and interferon (IFN)-γ production, as well as the production of OVA-specific antibody. However, gel-incorporated liposomes showed evidence of instability and similar in vivo immune responses to liposomes in gel formulations were induced by gel-based systems loaded with soluble OVA and QA. The immunogenicity of chitosan thermogels containing cubosomes, a more stable lipidic particulate system, was therefore examined. Similarly, all gel-based formulations produced comparable effector immune responses in experimental mice, irrespective of whether the antigen and immunopotentiator were present in gels within cubosomes or in a soluble form. This work demonstrates the potential for sustained release thermogelling systems and highlights the importance of matching the physicochemical and immunological properties of the particulate system to that of the depot.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Sarah
authors.initials: S
authors.lastname: Gordon
authors.forename: Katherine
authors.initials: K
authors.lastname: Young
authors.forename: Rachel
authors.initials: R
authors.lastname: Wilson
authors.forename: Shakila
authors.initials: S
authors.lastname: Rizwan
authors.forename: Roslyn
authors.initials: R
authors.lastname: Kemp
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004355:Drug Stability; D005434:Flow Cytometry; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry*; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D008081:Liposomes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010316:Particle Size; D062605:Quillaja Saponins; D012503:Saponins / Q000008:administration & dosage; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D020100:Hydrogels; D008081:Liposomes; D062605:Quillaja Saponins; D012503:Saponins; D014612:Vaccines; C046386:Quil A; D007371:Interferon-gamma; D010047:Ovalbumin; D048271:Chitosan