Microgels, colloidal networks of crosslinked water-soluble polymers with dimensions < 1 μm, have been demonstrated to be useful materials in a wide range of biomedical and environmental applications. In particular, temperature-responsive microgels based on poly(N- isopropylacrylamide) (PNIPAM) have attracted significant research interest in drug delivery applications. However, conventional precipitation-based PNIPAM microgels are functionally non-degradable, problematic for biomedical applications. To resolve this issue, a thermally- driven self-assembly approach based on hydrazide and aldehyde functionalized PNIPAM oligomers to form an acid-labile hydrazone bond was developed in the Hoare Lab to produce thermoresponsive, colloidally stable, monodisperse and degradable microgels.
In this thesis, the internal structure of these self-assembled microgels was investigated using small and ultra-small angle neutron scattering and surface force experiments. Contrary to expectations based on the assembly technique, all these characterization strategies suggested that self-assembled microgels have a homogeneously cross-linked internal structure. It is anticipated that these well-defined degradable and homogeneous nanoscale gel networks offer opportunities for addressing challenges in drug delivery, biosensing, and optics by exploiting the predictable diffusive and refractive properties of the homogeneous microgel networks. In addition, the co-self-assembly of a moderately hydrophobic anti-inflammatory drug (dexamethasone) during the microgel self-assembly process was demonstrated to enable five-fold higher drug encapsulation (75-80%) relative to the conventional partition/diffusion- based drug loading processes. This result addresses a key challenge in delivering hydrophobic drugs using conventional precipitation-based microgel systems due to the inherent hydrophilicity of the crosslinked network.
The potential of the self-assembly approach to fabricate multi-responsive smart microgels was demonstrated by incorporating pH-ionizable functional groups (via the copolymerization of acrylic acid and 2-dimethylaminoethylmethacrylate to introduce anionic and cationic charges respectively) into the hydrazide and aldehyde-functionalized precursor polymers prior to self-assembly. The self-assembled charged microgels showed the same pH- responsive swelling behaviours of conventional microgels, including amphoteric microgels that can be formed at any desired cationic:anionic charge density by simply mixing different ratios of cationic and anionic precursor polymers. Such microgels offer significant potential to improve the performance of microgels in applications demanding dual pH/temperature specific drug delivery. / Thesis / Master of Applied Science (MASc) / Medications can exist in many different forms. From pills to injections, existing drug delivery systems require a high frequency of drug administration and often result in low efficacy of drug once administered to the human body. Polymer-based drug delivery systems have the potential to improve this delivery. In particular, microgels, water-filled crosslinked polymer networks with a size less than one micron, offer promise as a drug delivery vehicle. The size and chemical composition of microgels can be tailored to enable their use in a wide array of drug delivery applications. In addition, microgels can be loaded with a therapeutic agent and transported in the blood stream to deliver drug at a rate and/or location tunable based on the internal structure of the microgel. “Smart” microgels have the particularly attractive ability to change their properties in response to certain environmental stimuli (i.e. temperature or pH). However, current smart microgel systems are non-degradable and would accumulate in the body, causing undesired side-effects. In this thesis, a new self-assembly approach has been used to produce degradable microgels with the potential to switch properties in response to both temperature and pH. Water-insoluble drugs can be encapsulated more efficiently with this method, and the dual-responsive behaviour is expected to improve our capacity to deliver drug at the rate and location desired in the body.
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23386 |
| Date | January 2018 |
| Creators | Mueller, Eva |
| Contributors | Hoare, Todd, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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