Sarah, Duggan (2015) The synthesis and characterisation of mucoadhesive polymeric systems using synthetic and natural polymers. PhD thesis, Waterford Institute of Technology.
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Abstract
Mucoadhesion is the binding of a material to a mucosal surface. The mucosal surface has a rate of absorption of up to four times that of the skin and, therefore, has great potential as a route of drug administration. Mucoadhesive polymeric drug delivery devices have been designed to allow for the slow and controlled release of a drug to a specific site, with fewer side effects and greater bioavailability in comparison to other methods of administration. In this project, mucoadhesive polymers were developed by modification through thiolation. Thiolation can increase mucoadhesive properties by up to 140-fold through the formation of disulphide bonds between the polymer and the mucosal layer. Three different polymers were thiolated to create these mucoadhesive systems: the synthetic polymers polyacrylic acid (PAA) and polyallylamine (PAAm), and the natural polymer gelatin. PAA was thiolated by reaction with L-cysteine and the crosslinker EDC. A novel method of regulating the thiol content of PAA by controlling the pH of the thiolation reaction was achieved which resulted in a range of thiolated polymers with varying degrees of thiolation. Gelatin was thiolated using a novel two-step reaction process whereby gelatin was initially aminated by reaction with EDC and ethylene diamine. This aminated gelatin was then thiolated with Traut’s reagent, creating a highly thiolated gelatin product. Finally, PAAm was directly thiolated with Traut’s reagent. Neither thiolated gelatin nor thiolated PAAm have been fully characterised for their mucoadhesive properties previous to this study. All thiolated polymers displayed improved cohesive and mucoadhesive properties in comparison to their unmodified counterparts. Thiol content altered the swelling ability, drug release profiles and thermal properties of the samples. The molecular weight of both PAA and gelatin were proven to have a marked impact on mucoadhesive properties. The potential toxicity of PAAm was lessened by thiolation. Thiolated polymers, both synthetic and natural, with varying degrees of thiolation, and differing swelling ability and drug release profiles were created, allowing for the design of a tailor-made mucoadhesive drug delivery system.
| Item Type: | Thesis (PhD) |
|---|---|
| Uncontrolled Keywords: | Mucoadhesive polymeric systems |
| Departments or Groups: | *NONE OF THESE* |
| Divisions: | School of Science > Department of Chemical and Life Sciences |
| Depositing User: | Derek Langford |
| Date Deposited: | 02 Oct 2015 13:21 |
| Last Modified: | 22 Aug 2016 10:27 |
| URI: | http://repository-testing.wit.ie/id/eprint/3109 |
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