title: Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems.
abstract: Thermoresponsive, particle-loaded, Poloxamer 407 (P407)-Pluronic-R® (25R4) or chitosan-methyl cellulose (MC) formulations were developed as single-dose, sustained release vaccines. The sol-gels, loaded either with a particulate vaccine (cubosomes) or soluble antigen (ovalbumin) and adjuvants (Quil A and monophosphoryl lipid A), were free-flowing liquids at room temperature and formed stable gels at physiological temperatures. Rheological results showed that both systems meet the criteria of being thermoresponsive gels. The P407-25R4 sol-gels did not significantly sustain the release of antigen in vivo while the chitosan-MC sol-gels sustained the release of antigen up to at least 14 days after administration. The chitosan-MC sol-gels stimulated both cellular and humoral responses. The inclusion of cubosomes in the sol-gels did not provide a definitive beneficial effect. Further analysis of the formulations with small-angle X-ray scattering (SAXS) revealed that while cubosomes were stable in chitosan-MC gels they were not stable in P407-25R4 formulations. The reason for the mixed response to cubosome-loaded vehicles requires more investigation, however it appears that the cubosomes did not facilitate synchronous vaccine release and may in fact retard release, reducing efficacy in some cases. From these results, chitosan-MC sol-gels show potential as sustained release vaccine delivery systems, as compared to the P407-25R4 system that had a limited ability to sustain antigen release.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Thunjiradasiree
authors.initials: T
authors.lastname: Kojarunchitt
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark.
authors.forename: Stefania
authors.initials: S
authors.lastname: Baldursdottir
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Australia.
authors.forename: Yao-Da
authors.initials: YD
authors.lastname: Dong
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Australia.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand; Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand. Electronic address: sarah.hook@otago.ac.nz.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hook
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005782:Gels / Q000737:chemistry* / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D008297:Male; D008747:Methylcellulose / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D020442:Poloxamer / Q000737:chemistry* / Q000494:pharmacology; D012212:Rheology; D053838:Scattering, Small Angle; D013696:Temperature; D014612:Vaccines / Q000737:chemistry* / Q000494:pharmacology; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D014612:Vaccines; D020442:Poloxamer; D008747:Methylcellulose; D010047:Ovalbumin; D048271:Chitosan
keywords: Chitosan; Cubosomes; Nanoparticle; Poloxamer 407; Sustained release; Vaccine delivery