<p> Photoresponsive polymers can act as controllable drug delivery systems that may
revolutionize ophthalmic drug delivery for disease treatment in the posterior segment of
the eye. Localized, controlled drug delivery devices have significant therapeutic
advantages for treating diseases of back of the eye by increasing patient compliance and
maintaining therapeutic levels of drug in the tissue. Sustained-release delivery systems
that respond to light/laser stimuli are under development to control the rate of delivery
resulting in a tuneable treatment profile ideal for retinal diseases. The use of light as a
crosslinking mechanism has the potential to create unique materials with controllable
swelling, degradation and diffusion properties. </p> <p> This thesis investigates the synthesis and development of universal, graftable
PEG-anthracene molecules and their applications in photosensitive alginate and
hyaluronate (HA) "photogels". Anthracene undergoes reversible dimerization with
wavelengths above 300 nm and de-dimerization/dissociation below 300 nm; due to its
well-understood chemistry and symmetry, it was used as a starting point and proof-ofconcept
for the synthesis of reversible dimerizing crosslinkers that may be generically
grafted to different polymers to cause crosslinking/decrosslinking. After synthesis, watersoluble
PEG-anthracene macromolecules were grafting via carbodiimide chemistry to the
carboxyl groups along the polymer backbone of alginate and HA at various densities to
create viscous liquids or gels with good handling properties. </p> <p> Light irradiation can be used to control the swelling and effective crosslinking
density of the photogels which in tum can control drug delivery from photocrosslinked hydro gels as illustrated through the decrease or increase in the delivery of a variety of low
molecular weight (<1000 Da) and high molecular weight (>10,000 Da) model drug
compounds from both alginate and HA photogels with various light treatments. Novel
loading mechanisms were developed through the loading of compounds into
uncrosslinked gels followed by crosslinking 365 nm exposures to "lock" in the model
drug compounds. Diffusion coefficients effectively compared the different systems
showing increase exposures of 365 nm resulted in greater decrease in release of
compounds demonstrating the ability to fine-tune release rates. Different formulations
and control gels demonstrate a variety of different release profiles. The photogels were
valuable long-term controlled release systems (>80 days) that also demonstrate high
cytocompatibility when grown with ophthalmic cell lines. </p> <p> Novel photoresponsive biomaterials for smart delivery of therapeutics which use
light-controlled crosslinking and decrosslinking mechanisms have been developed. The
PEG-anthracene graftable photocrosslinkers show the ability to introduce photocontrolled
crosslinking into hydrogel systems. While anthracene as the photodimerizer
and alginate and HA as the bulk materials are used as a proof-of-concept in this work, this
grafting system can be further manipulated to include new photosensitive dimerizers and
other applicable polymers. The ability to use light stimuli to control release rates in a
continual fashion, rather than having delivery that is strictly on or off, is a valuable
finding that may lead to the development of drug delivery systems that can be catered
towards individuals and the progression of their disease. </p> / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/19447 |
| Date | 11 1900 |
| Creators | Wells, Laura |
| Contributors | Sheardown, Heather, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
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