Pharmaceutical formulations as immunological adjuvants

O'Hagan, Derek Thomas (1987) Pharmaceutical formulations as immunological adjuvants. PhD thesis, University of Nottingham.

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Abstract

The aim of this work was to enhance the immune responses to ovalbumin (OVA) following its oral administration, by the association of the protein with colloidal carriers, which may protect the protein from degradation in the gastrointestinal tract and/or facilitate its uptake across the intestine.

An enzyme linked immunosorbent assay (ELISA) was established for the determination of rat anti-OVA antibodies and an immunisation protocol was established to induce a statistically significant salivary antibody response to OVA in the rat. A radioimmunoassay for the determination of rat anti-OVA antibodies was also established, to confirm the ELISA results. Methods were established to determine the extent of incorporation or adsorption of OVA into or onto the colloidal carrier formulations.

OVA was incorporated into liposomes and polyacrylamide microparticles, and adsorbed to poly 2-butylcyanoacrylate particles, and gastrically intubated into separate groups of experimental rats. The primary and memory immune responses, both sera and saliva, were compared for each formulation with suitable control and blank groups.

All colloidal carriers induced enhanced immune responses to OVA following oral administration in the rat, when compared with the respective control group responses. However, the enhancement for the liposomal group was not statistically significant when assessed in an Unpaired Student 't' test.

The effect of particle size on the immune responses was assessed by the oral administration of 100 nm and 3pm poly 2-butylcyanoacrylate particles with adsorbed OVA.

An electron microscopy study was undertaken with gold labelled poly 2-butylcyanoacrylate particles in an attempt to demonstrate the uptake of particles by M-cells overlying the Peyers' patches in the rat intestine.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Davis, S.S.
Palin, K.
Subjects: Q Science > QP Physiology > QP1 Physiology (General) including influence of the environment
R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 13211
Depositing User: EP, Services
Date Deposited: 19 Apr 2013 10:18
Last Modified: 16 Sep 2016 18:02
URI: http://eprints.nottingham.ac.uk/id/eprint/13211

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