Murdan, Sudaxshina; (1998) Non-ionic surfactant-based organogels: Their structures and potential as vaccine adjuvants. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The research described in this thesis was undertaken to investigate firstly, the gelation of certain organic solvents by the non-ionic surfactant, sorbitan monostearate, and secondly, to investigate the immunoadjuvanticity of multi-component vesicle-in- water-in-oil (v/w/o) organic gels. Sorbitan monostearate causes the gelation of a number of organic solvents, for example hexadecane and isopropyl myristate, to produce opaque, semi-solid, thermoreversible, physical organic gels (organogels). The organogel's microstructure is a 3-dimensional network of tubules dispersed in the organic fluid phase. Gelation of organic solvents occurs on cooling a hot (60°C) solution/suspension of the gelator. Cooling results in reduced solvent-surfactant affinities and consequent surfactant self-assembly into tubules which interact and form the 3-dimensional network. Inclusion of a second surfactant, such as the hydrophilic polysorbate 20, in hexadecane gels increases the solubility of sorbitan monostearate in the solvent, enhances gel stability and results in star-shaped cluster arrangements, presumably of the surfactant tubules. An aqueous phase, water itself or a niosome suspension containing entrapped antigens, can be added to the organogel to produce the multi-component systems, water-in-oil (w/o) and vesicle-in-water-in-oil (v/w/o) gels respectively. The aqueous phase is located within the hydrophilic surfactant tubules and consequently, aqueous electroconductive channels are established in the organic gel. A v/w/o gel entrapping antigen was investigated for its immunoadjuvant properties. In vivo clearance studies in mice showed the v/w/o gel acts as an antigenic depot at the site of injection after intramuscular injection and releases the model antigen, bovine serum albumin, over a period of days. Immunogenicity studies using the influenza virus haemagglutinin (HA) subunit as the antigen, showed that w/o and v/w/o organogels significantly enhance the primary and secondary anti-HA antibody titres compared to aqueous and niosome suspensions. However, when a lower antigen dose is used, the v/w/o gel does not show immunoadjuvant abilities. This reflects the need for a minimum antigen load per vesicle for adjuvanticity.

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