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AbstractAbstract
[en] Polymer microparticles have tremendous potential as the next generation of adjuvant systems to replace the only adjuvant currently widely registered for human use, alum. Based on aluminium salts, alum adjuvants work as short-term depots of adsorbed protein/antigens that slowly 'leak' into the body's immune system, inducing immunity by invoking a humoral response. The main disadvantage of alum adjuvants is that they do not raise sufficient antibody levels to induce long-term immunity. Hence, booster administrations are required. This drawback presents the biggest factor in the failure of many vaccination programmes. Polymer microparticulate systems can be fashioned to deliver sub-unit and peptide antigens in a continuous or controlled rate over a desired period of time, avoiding the need for booster doses. The design of mucosal vaccines is now centred upon the use of these polymeric carriers. The mucosal route for immunisation has many advantages over the more conventional systemic route, the most important of which, is the induction of both humoral and cellular immunity. Polymer microspheres of sizes <10μm are especially good candidates as oral vaccine adjuvants as they are taken up by the M cells of the Peyer's patches in the intestine. Numerous studies have been carried out on microspheres into which antigens have been encapsulated or entrapped. There are, however, problems associated with loss of antigenicity since formulation procedures involve the use of organic solvents and harsh shearing methods. Additionally, these antigens may be further degraded when the polymer material itself degrades in vivo and produces acidic species. A novel adjuvant system that avoids the above problems is currently being evaluated. Poly(l-lactide) (PLLA) polymeric lamellar substrate particles (PLSP) are promising as novel adjuvants for the controlled release of antigens. Reports have shown that the adsorption of antigens onto the surface of these particles can induce cellular immune responses in animal models. The fate and efficiency of the PLSP as adjuvants and antigen carriers in vivo depends on their physicochemical properties. The type of polymer material used, which includes factors such as molecular weight and crystallinity; and the manufacturing processes involved, affect these properties. Therefore it is crucial to determine and control the critical parameters. The surface properties of the PLSP determine their adsorptive, retention and release characteristics; hence it is important that these surfaces are optimally tailored for their specific purposes. In this thesis, process variables such as temperature, polymer molecular weight, polymer concentration, solvent type, pH and mode of non-solvent addition are varied in order to ascertain the critical parameters. The surfaces of PLSP are modified by adsorbing non-ionic, anionic natural, and cationic surfactants and polymers. The efficiency and result of surface modification techniques are then investigated by analysing some of the modified samples using FTIR-ATR and performing protein adsorption studies. Dynamic adsorption studies using surface plasmon resonance (SPR) has helped elucidate the adsorption profiles of unmodified and PEG surface-modified PLSP. (author)
Source
2002; [vp.]; University of Nottingham; Nottingham (United Kingdom); Available from British Library Document Supply Centre- DSC:DXN058968; Country of input: International Atomic Energy Agency (IAEA); Thesis (Ph.D.)
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Miscellaneous
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Thesis/Dissertation
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