Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.614512
Title: Development and physical characterisation of polyethylene glycol glycerides-based gel formulations for macromolecule delivery
Author: Codoni, D.
Awarding Body: University of East Anglia
Current Institution: University of East Anglia
Date of Award: 2013
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Abstract:
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 delivery.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.614512  DOI: Not available
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