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: Users 2259 not found.
Date Deposited: 12 Jun 2014 13:50
Last Modified: 12 Jun 2014 13:50


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