In this thesis, glucose responsive hydrogels based on cross-linked dextran molecules were studied to determine the diffusion rate of an insulin analogue. Investigations of the interaction between concanavalin A and dextran, both in free solution and in the form of glucose responsive hydrogels were conducted. The free solution results have shown that there is an increase of association constant between concanavalin A and dextran when the molecular mass of the dextran is increased. Free solution viscometric tests have shown that increasing the molecular mass or the concentration of the dextran increases the viscosity. The hydrogels have been shown to form for dextrans of molecular mass 43kD or greater. Smaller molecular mass dextrans were found to coalesce into small beads which appeared to prevent hydrogel formation with these materials. Experiments conducted with hydrogel membranes in a diffusion cell have shown that the batch to batch reproducibility of hydrogel transport properties is low. This is partly due to the weak mechanical nature of the hydrogel and partly due to the heterogeneous nature of the precursor dextrans. However, clear evidence of glucose enhanced transport was obtained and these results were compared with predictions obtained from a theoretical model of gel permeability that accounts for competitive displacement of affinity cross links. Oscillatory rheological tests of gelation mixtures which showed an increase in complex viscosity at the gel point with increasing molecular mass of dextran were in agreement with empirical observations that gels formed from the highest molecular mass dextrans were more physically robust and easier to handle. Swelling rate experiments have shown that the rate of hydration of a hydrogel in the presence of glucose is decreased due to the osmotic pressure of the glucose. This work has shown that the multivalent nature of concanavalin A may not be a necessary pre-requisite for this type of hydrogel due to spatial constraints decreasing the number of potential affinity bonds per tetramer. In-house production of more tightly defined dextrans (molecular mass and branching ratio) might be expected to reduce heterogeneity and improve the reproducibility of this type of hydrogel membrane.
|Date of Award||1 Jan 2009|
|Sponsors||Engineering and Physical Sciences Research Council|
|Supervisor||John Hubble (Supervisor)|
- gel swelling