Intranasal administration of diphtheria toxoid. Selecting antibody isotypes using formulations having various lipophilic characteristics

Abstract

Non-ionic excipients, having different lipophilicity, were compared for their selection of immunological response in different organs and biological fluids. In order to express the lipophilicity of the formulation, the balance between the size and strength of the hydrophilic and lipophilic groups was used, called the hydrophile-lipophile balance (HLB) value. Mice were immunized and boosted intranasally with diphtheria toxoid, and samples were taken from the blood, spleen, nasal wash, lungs, saliva, stomach, duodenum, jejunum and the skin. In general, formulations which were highly hydrophilic and highly lipophilic were not able to augment the immunological response markedly (except for IgA). Formulations having intermediate HLB values, e.g. around 9.0, stimulated both IgG 1 and IgG 2a production, where the HLB = 5.5 formulation seemed to stimulate mainly IgG 2b and IgG 3 antibody production. On the other hand, comparing the IgA concentration in various samples with respective IgG level, increasing HLB value seems to augment the production of mainly IgA antibodies. The results indicate that the antibody isotypes may be controlled, using variations in the hydrophile-lipophile balance value.