An efficient delivery system and patient compliance are two of the most important factors for any drug delivery system design to be successful. The current standard, particularly to the ocular anterior segment, are topical applications including eye drops. However, due to ocular physical barriers including blinking, the varying tear film layers, and the structure of the corneal epithelium, less that 5% of drug reach the target tissue from a single eye drop dose. While most treatment regiments combat this with increased frequency of dosage and higher than needed concentrations, the need for a more efficient and controlled system has been recognized to reduce the risk of possible side effects. Contact lenses (CL) have been a widely discussed potential drug delivery device given their accepted use in the population, their ability to hold drug, as well as their placement on the ocular surface.
The current work focuses on testing a novel delivery system using CLs with the incorporation of drug specific oligonucleotide chains known as aptamers on the surface of the lenses. This application of contact lenses is aimed at capitalizing on the strong affinity of aptamers to hold drug on the surface of the lenses until they are applied to the eyes. The aptamers were covalently attached to the surface via the activation of the hydroxyl groups on pHEMA as a model lens material using 1’1-carbonyldiimidazone CDI chemistry and subsequent reaction with the amine group on the 5' end of the aptamer. The presence of aptamers was confirmed using 6-carbofluorescein (6-FAM) fluorescence detection and x-ray photoelectron spectroscopy (XPS). The release of kanamycin B in comparison to regular pHEMA gels using a soaking uptake method was assessed.
In this work, aptamers were confirmed through fluorescence to have been successfully reacted onto the surface, however XPS was not able to confirm a consistent reading. This may have been due to low initial amounts of aptamer or uneven distributions along the surface. The efficiency of the aptamer reaction was not tested and would need to be further investigated. The contact angle had a significant change with increased hydrophilicity at 60.7 ± 1.55° compared to 66.6 ± 0.67°, however physically it should not affect wettability. The lower aptamer amounts resulted in no significant difference during drug release. Kanamycin B was detected using liquid chromatography mass spectroscopy (LCMS) with a reverse phase method using a C18 column however quite a few errors in the methodology led to the conclusion that this method of drug release requires further investigation. It is recommended an aptamer-surface reaction efficiency be determined with the use of a much larger starting aptamer amount, as well as a follow up drug release. / Thesis / Master of Applied Science (MASc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/25890 |
| Date | January 2020 |
| Creators | Shaw, Aakash |
| Contributors | Sheardown, Heather, Chemical Engineering |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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