Thesis
Surface modification and in vitro evaluation of protein microspheres
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 1993
- Thesis identifier
- T7851
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- The Malvern 2600C laser droplet and particle sizer was used to assess the in vitro behaviour of various microspherical preparations, predominantly albumin, when suspended in a solutions of proteases. Proteolytic degradation of microspheres was assessed by comparing the T₁ and T₅₀ values assigned to a typical measured volume concentration versus time profile obtained from each experiment. Statistical evaluation of the data showed a positive correlation between the amount of glutaraldehyde used during preparation and the resistance of the microspheres to proteolytic degradation. Evaluation of the data also showed that in vitro degradation was independent of the size of the microspheres in suspension. A water soluble carbodiimide, 1-ethyl-3-[3- dimethylamino-propyl] carbodiimide (EDC), was used to effect modification of -COOH groups on human serum albumin microspheres such that the covalent attachment of a non-ionic surfactant could be facilitated. Initially it was attempted to optimise the process by means of an assay method for EDC. This ultimately proved inadequate and was replaced by using ¹⁴C-glycine ethylester as a model nucleophile, allowing the quantitative evaluation and optimisation of the proposed processes. It was found that the covalent attachment of ¹⁴C-glycine ethyl ester was augmented by the pre-treatment of HSA microspheres with succinic anhydride. The non-ionic surfactant, methoxypolyethyleneglycol-amine (mPEG- amine) , replaced the model nucleophile under the optimum conditions in an attempt to modify the surface properties of HAS microspheres. Each stage of the modification process was assessed in vitro using the Malvern technique. It was shown that EDC increased the resistance of HSA microspheres to proteolytic degradation probably due to intraparticulate bonding. The addition of succinic anhydride decreased the resistance of HSA microspheres to proteolytic degradation. This may have been due to the displacement effects of the succinic anhydride at the complex formed between glutaraldehyde and amine residues during microsphere preparation. Modification of HSA microspheres with mPEG amine increased the resistance of the microspheres to proteolytic degradation compared with the relevant controls. Further evidence for the presence of the polymer on the surface was obtained by static secondary ion mass spectroscopy of the modified HSA microspheres.
- Advisor / supervisor
- Willmott, Nigel
- Halbert, Gavin W.
- Resource Type
- DOI
- EThOS ID
- uk.bl.ethos.881233
- Funder
- Embargo Note
Relations
Items
| Thumbnail | Title | Date Uploaded | Visibility | Actions |
|---|---|---|---|---|
|
|
File | 2025-08-05 | Private |