Natural polymers such as polysaccharides have been used as self-assembled matrices for drug delivery. Modified high amylose starch tablets swell to a limit when submerged in water, yielding a hydrogel with quasi-reversible viscoelastic properties. Such tablets display slow-release properties with a near zero-order drug delivery kinetics. Mechanical properties, electron microscopy imaging and swelling behavior have been investigated. Results from the foregoing investigations and from 13C CP/MAS NMR studies, which showed a clear transition from amorphous to crystalline organization upon wetting, were used to propose a model. The latter proposes that the viscoelastic hydrogel is formed due to the propensity of amylopectin and amylose, the two components of starch, to organize into double helices. The so formed pseudo-crosslinks, as water penetrates the dry tablet, explain the shape retention (limited swelling). This model was tested using Curdlan, a beta-1,3-glucan that is known to crystallize as triple helices. Studies on Curdlan tablets demonstrated limited swelling and shape retention, but unsuitable mechanical properties. This supported the model and added a feature that takes into account the heterogeneous nature of starch as an important factor in the obtention of a good viscoelastic hydrogel. / Because hydrophobic drugs are difficult to release by diffusion through matrices of hydrophilic polysaccharides, synthesis of compatibilizers was undertaken. Using a natural hydrophobic polyester: poly([R]-3-hydroxybutyric acid), PHB, possessing a high enthalpy of crystallization, a self-assembly amphiphilic system was created. Diblock copolymers of monomethoxy poly(ethylene glycol), mPEG and PHB were synthesized in a one-step, solvent-free, transesterification reaction. The resulting diblock copolymers were used to form colloidal suspensions of nanoparticles that are potential drug carriers and compatibilizers.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.84422 |
| Date | January 2002 |
| Creators | Ravenelle, François |
| Contributors | Marchessault, Robert H. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001983431, proquestno: AAINQ88566, Theses scanned by UMI/ProQuest. |
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