Owen R Davies

University of Nottingham, Nottingham, ENG, United Kingdom

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Publications (7)39.29 Total impact

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    ABSTRACT: Single shot vaccines of tetanus toxoid (TT) were manufactured using the NanoMix process - a low temperature solvent free encapsulation technology using supercritical fluids. The formulations were injected into mice, and compared to multiple injections of a commercially available alum adsorbed TT vaccine. After 5 months the antibody titres were found to be similar for both the alum adsorbed and microparticle formulations, demonstrating for the first time the potential of formulating antigens in PLA microparticles using the supercritical fluid (NanoMix) technique to produce single shot vaccines. The results are likely to be due to the maintenance of toxoid bioactivity and some degree of sustained release of the encapsulated antigens, resulting in repeated stimulation of antigen presenting cells eliminating the need for multiple immunisations. This demonstrates the potential of this supercritical fluid processing technique to reduce the need for booster doses in a vaccine regimen.
    International Journal of Pharmaceutics 07/2011; 413(1-2):147-54. DOI:10.1016/j.ijpharm.2011.04.053 · 3.65 Impact Factor
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    ABSTRACT: In this paper, we describe surface modification of poly( D,L-lactide- co-glycolide) (PLG) microspheres, intended for DNA vaccine application, with two functionalities: a steric stabilizing component, provided by poly(vinyl alcohol) (PVA) and a cationic component, aimed at subsequent DNA surface loading. The cationic functionality arises from polycations, such as PEI, poly( L-lysine), trimethyl chitosan, and (dimethylamino)ethyl methacrylate, introduced into the water phase of classical oil-in-water (o/w) solvent evaporation method of PLG microsphere fabrication. By systematic evaluation of production variables, a system was produced with balanced properties in terms of microsphere size appropriate for uptake by antigen presenting (e.g., dendritic) cells, colloidal stability, and relatively high DNA loading. The polycation (PEI) molecular weight and preparation concentration were both found to increase the surface polycation content and DNA binding capacity; however, they lead to an increased tendency for aggregation, particularly when the microsphere size was decreased. DNA loading of almost 100% efficiency was achieved under optimized conditions in physiologically acceptable buffers, resulting in a surface DNA loading appropriate for vaccine purposes. A further increase in surface DNA loading was however associated with an increase in the particles negative potential, indicating the surface presence of DNA charges not neutralized by the polycation and hence potentially not protected from in vivo enzymatic degradation. The internalization of surface-loaded DNA into the target cells was confirmed by monitoring fluorescent DNA after the microspheres were endocytosed by the cells in culture.
    Langmuir 08/2008; 24(14):7138-46. DOI:10.1021/la703735n · 4.46 Impact Factor
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    ABSTRACT: Supercritical CO(2) has the potential to be an excellent environment within which controlled release polymers and dry composites may be formed. The low temperature and dry conditions within the fluid offer obvious advantages in the processing of water, solvent or heat labile molecules. The low viscosity and high diffusivity of scCO(2) offer the possibility of novel processing routes for polymer drug composites, but there are still technical challenges to overcome. Moreover, the low solubility of most drug molecules in scCO(2) presents both challenges and advantages. This review explores the current methods that use high pressure and scCO(2) for the production of drug delivery systems and the more specialized application of the fluid in the formation of highly porous tissue engineering scaffolds.
    Advanced Drug Delivery Reviews 03/2008; 60(3):373-87. DOI:10.1016/j.addr.2006.12.001 · 15.04 Impact Factor
  • Owen R. Davies · Maria Marlow · Snow Stolnik ·
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    ABSTRACT: Novel macroporous and surface functionalized polymeric microparticles were prepared using a modified emulsion technique. The microparticles were able to surface load DNA and have a range of potential applications in drug delivery of biologics and tissue engineering.
    Soft Matter 01/2008; 4(8). DOI:10.1039/b805421e · 4.03 Impact Factor
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    J A Winter · O R Davies · A P Brown · M C Garnett · S Stolnik · D I Pritchard ·
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    ABSTRACT: A vaccine against the human hookworm Necator americanus is urgently required to reduce hookworm-induced morbidity in endemic areas. In the present study, recombinant hookworm calreticulin, a nominated vaccine candidate, has been tested in mice. Mice given calreticulin had 43-49% fewer worms in their lungs, compared to non-vaccinated controls, following challenge infection with infective hookworm larvae. These levels of protection were achieved in the absence of adjuvant following intraperitoneal administration of three doses of 15 microg antigen. Antigen was also encapsulated in PLG microparticles. Encapsulated calreticulin elicited higher levels of anti-calreticulin IgG1 than free antigen but failed to induce protective immunity. The protection induced by free calreticulin was associated with low levels of serum IgE and moderate lung eosinophilia whilst administration of calreticulin-loaded microparticles was associated with high levels of serum IgE and higher lung eosinophil activity, suggesting that the classical Th2 phenotype may not always be associated with protective immunity, albeit in experimental necatoriasis.
    Parasite Immunology 05/2005; 27(4):139-46. DOI:10.1111/j.1365-3024.2005.00756.x · 2.14 Impact Factor
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    ABSTRACT: In this study, we use supercritical carbon dioxide as a processing medium for the fabrication of poly(DL-lactic acid) P(DLLA) microparticles that encapsulate a protein material. We have previously demonstrated that this polymer and a dry powder of a protein can be mixed under supercritical carbon dioxide conditions (above 31.1 degrees C and 73.8 bar) and that the protein component retains its biological activity. In this paper, we progress the work to demonstrate that the plasticized polymer and dry powder protein mixture can be sprayed to form solid polymer particles that encapsulate the protein. Particle size range is between 10 and 300 microm after spraying. Ribonuclease A and lysozyme were encapsulated in the polymer without significant loss of enzymatic activity. Biological assays of insulin and calcitonin confirm retention of activity after fabrication of the microparticles and release of the peptides/proteins.
    Journal of Controlled Release 02/2005; 101(1-3):85-92. DOI:10.1016/j.jconrel.2004.07.017 · 7.71 Impact Factor
  • O. R. Davies · D. Armitage · P. Williams · A. Brindley · M. Marlow · S. Stolnik ·
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    ABSTRACT: Science Proceedings of the British Pharmaceutical Conference
    Journal of Pharmacy and Pharmacology 01/2003; 55:S.47-S.47. · 2.26 Impact Factor