Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens?
Multi-component organogels formed using the non-ionic surfactant sorbitan monostearate as gelator have been formulated to contain niosomes. The purpose of this study was to evaluate the potential of these vesicle-in-water-in-oil (v/w/o) gels as delivery vehicles for vaccines. Bovine serum albumin (BSA) and haemagglutinin (HA) were used as model antigens in depot and immunogenicity studies respectively. The complex gels were prepared by the addition of a hot (60 degrees C) aqueous niosome suspension (v/w) to the sol phase (o, an organic solution of the gelator); a vesicle-in-water-in-oil (v/w/o) emulsion was produced which cools to an opaque, semi-solid, thermoreversible v/w/o gel. Light microscopy of the organogel revealed that the microstructure consists of a tubular network of surfactant aggregates in the organic medium, the niosome suspension being dispersed in these surfactant tubules. Therefore, in such gels, the vaccine is thought to be entrapped in the niosomes, themselves located within the sorbitan monostearate tubular network in the organic medium. In vivo, a depot effect was observed following intramuscular administration of the gel containing the entrapped bovine serum albumin, cleared from the injection site over a period of days. The relatively short-lived nature of the depot was thought to arise due to interactions between the gel and the local interstitial fluid which results in gel disintegration in situ. Thus, the niosomes containing antigens are believed to be released from the organic gel. Immunogenicity studies showed that the v/w/o gel as well as one of the controls, the water-in-oil (w/o) gel, possess immunoadjuvant properties and enhance the primary and secondary antibody titres (of total IgG, IgG1, IgG2a and IgG2b) to haemagglutinin antigen. As far as humoral immunity is concerned, the w/o gel showed stronger immunoadjuvant properties compared to the v/w/o gel, being effective at a lower antigen dose i.e 0.1 microg HA.
Murdan
S
S
Centre for Drug Delivery Research, School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Gregoriadis
G
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Florence
A T
AT
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients; D005782:Gels; D006388:Hemagglutinins / Q000008:administration & dosage / Q000276:immunology; D006601:Hexoses; D009980:Influenza A virus / Q000276:immunology; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011136:Polysorbates; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013501:Surface-Active Agents
D000276:Adjuvants, Immunologic; D000941:Antigens; D000956:Antigens, Viral; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D006388:Hemagglutinins; D006601:Hexoses; D011136:Polysorbates; D013501:Surface-Active Agents; D012710:Serum Albumin, Bovine; C009298:sorbitan monostearate