TY - JOUR

T1 - Chitosan hydrogels containing liposomes and cubosomes as particulate sustained release vaccine delivery systems

AU - Gordon, Sarah

AU - Young, Katherine

AU - Wilson, Rachel

AU - Rizwan, Shakila

AU - Kemp, Roslyn

AU - Rades, Thomas

AU - Hook, Sarah

N1 - Funding Information: This research was financially supported by the University of Otago. S.G. gratefully acknowledges the University of Otago and the National School of Pharmacy for the provision of a University of Otago Postgraduate Scholarship and a Ph.D. stipend, respectively.

PY - 2012/9

Y1 - 2012/9

N2 - 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.

AB - 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.

KW - Immune response

KW - Particulate delivery systems

KW - Sustained release delivery systems

KW - Thermosensitive hydrogel

UR - http://www.scopus.com/inward/record.url?scp=84865225071&partnerID=8YFLogxK

U2 - 10.3109/08982104.2011.637502

DO - 10.3109/08982104.2011.637502

M3 - Journal article

C2 - 22188610

AN - SCOPUS:84865225071

VL - 22

SP - 193

EP - 204

JO - Journal of Liposome Research

JF - Journal of Liposome Research

SN - 0898-2104

IS - 3

ER -