Development and physical characterisation of polyethylene glycol glycerides-based gel formulations for macromolecule delivery

Codoni, D (2013) Development and physical characterisation of polyethylene glycol glycerides-based gel formulations for macromolecule delivery. Doctoral thesis, University of East Anglia.

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    Lipid-based delivery systems offer many advantages on enhancing the bioavailability of
    protein/peptides. Gelucire 50/13 is a complex mixture of glycerides and PEG. It is mainly
    used in solid oral formulations for delivering small molecular weight drugs. The purpose of
    this project was to develop novel uses of Gelucire as a liquid crystalline-based gel-forming
    material for protein/peptide delivery. A thorough physical and mechanical characterisation of
    the gels (with and without lysozyme as a model protein) was conducted using a combination
    of analytical techniques including ATR-FTIR, DSC, relaxometry NMR, rheological and
    texture analyser, and imaging analyses (SEM, AFM, and cryo-TEM). The results
    demonstrated the sophisticated microstructures of the gels due to the formation of various
    liquid crystalline phases that change with the gel water content. The gels with low water
    contents are characterised by highly restricted diffusion of water molecules in the gels, while
    water-rich and lipid-rich phases are present in the gels with medium to high water contents.
    The ordered liquid crystalline structures with lipid-rich and water-rich domains provide
    excellent carrier properties for hosting proteins/peptides. The effect of water content on the
    microstructure, physical properties and in vitro performance of the gels prevails on other
    effects such as gel preparation method and protein incorporation. The wide range of
    microstructures of the gels enables the mucoadhesive properties and release profiles of
    lysozyme from the gels to be controlled. Highly stable disc-shaped nanoparticles were
    produced from the Gelucire gels using a single-step and solvent-free method without the
    addition of stabilisers. In vitro cell culture studies revealed high tolerance to and rapid uptake
    of the gel nanoparticles by Caco-2 cells. The good protein encapsulation efficiency and the
    retained biological activity of lysozyme indicates considerable potential for these
    nanoparticles to be a new class of safe, low-cost and effective carriers for protein/peptide

    Item Type: Thesis (Doctoral)
    Faculty \ School: Faculty of Science > School of Pharmacy
    Depositing User: Mia Reeves
    Date Deposited: 12 Jun 2014 14:50
    Last Modified: 12 Jun 2014 14:50

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