The pursuit of optimizing soft contact lens performance has been extensive, given that approximately over 140 million contact lens wearers globally seek the convenience and visual acuity they offer. However, a persistent challenge is the prevalence of ocular dryness and discomfort experienced by almost half of these wearers, particularly towards the end of the day. The occurrence of these symptoms is primarily attributed to diminished compatibility between the contact lens and the ocular surface leading to contact lens discontinuation. A promising method to improve overall contact lens properties is to incorporate novel monomers with unique functionalities during the initial manufacturing stage. Monomers bearing ionic functional groups have been extensively explored to improve bulk and surface properties of biomaterials. The incorporation of cationic and zwitterionic monomers in the fabrication of hydrogel materials has shown to have anti-fouling and anti-bacterial properties and improved surface wetting. In this work, a series of novel materials using cationic and zwitterionic monomers were prepared and their impact on bulk and surface properties of contact lens materials were assessed. Furthermore, the impact of a novel hydrophilic silicone-based monomer bearing zwitterionic phosphocholine was investigated for water-based extraction, physiochemical and structural stability in candidate contact lens materials. In Chapter 2, a library of eleven positively charged (cationic) and electrically neutral with both positive and negative charges (zwitterionic) functional methacrylate ester monomers was produced through the reaction of 2-(dimethylamino) ethyl methacrylate (DMAEMA) with different alkyl halides. The Menshutkin reaction was carried out with a high level of success, resulting in moderate to high yields of the desired monomers. The monomers were purified and characterized using analytical techniques, including 1H-NMR (proton nuclear magnetic resonance), 13C-NMR (carbon-13 nuclear magnetic resonance), LCMS (liquid chromatography-mass spectrometry), and XRD (X-ray diffraction). Six monomers were chosen based on controlled end group hydrophilicity and chain length to investigate the relationship between chemical structure and overall performance in hydrogel and silicone hydrogel systems. In Chapters 3 and 4, model hydrogel and silicone hydrogel systems via UV free-radical polymerization at increasing input concentrations (10 and 20 wt%) were manufactured using the monomers and HEMA (hydrogel) or HEMA + SIGMA (silicone hydrogel). The novel materials demonstrated an increase in bulk equilibrium water content, reduced contact angle and nonspecific lysozyme and albumin adsorption, while maintaining optical transparency at higher than 90%. In vitro studies demonstrated the ionically charged hydrogel materials did not show any toxicity to human corneal epithelial cells. In Chapter 5, a super hydrophilic silicone-based SIGMAPC monomer was synthesized using the siloxane functional monomer (SIGMA) as the main building block. The introduction of the novel hydrophilic SIGMAPC monomer led to significant improvements in the silicone materials. The hydrogels showed increased water content and reduced water contact angles, indicating their superior hydrophilicity. Moreover, the rate of dehydration was decreased, and the nonspecific deposition of lysozyme and albumin was minimized. Importantly, the optical transparency of the hydrogel silicone remained above 90%. Based on these findings, it can be concluded that the siloxane-based monomer bearing a zwitterionic phosphocholine has great potential for applications in contact lenses, given its desirable properties and biocompatibility. Furthermore, in Chapter 6, 31P-NMR and weight extraction analysis showed model contact lens materials made with SIGMAPC were effectively extracted in aqueous media at elevated temperature. Candidate materials showed good dimensional and optical stability pre- and post-thermal sterilization and over 6-month storage period. / Thesis / Doctor of Philosophy (PhD)

The wettability of contact lenses has become an area of intense research, with the belief that the more "hydrophilic" or wettable the lens surface is, the more comfortable the lens may be, as the posterior surface of the eyelid will move more smoothly over it, hence increasing comfort. <br /><br /> There are many ways to assess the wettability of a given material, namely sessile drop,¹ captive bubble ² or Wilhelmy plate. ³ This thesis used the sessile drop method to determine the surface wettability of various hydrogel contact lens materials, by measuring the advancing contact angle made between the lens surface and a pre-determined volume of HPLC-grade water. This was followed by measuring the surface wettability following periods in which the lens materials were soaked in various contact lens care regimens. Further studies determined wettability of lens materials after various periods of in-eye wear and finally a study was undertaken to evaluate if a novel biological technique could be used to differentiate proteins that deposit on hydrogel lens materials that may affect wettability and cause discomfort. <br /><br /> A variety of hydrogel lenses, taken directly from their packaging and after soaking in various care regimens, were analyzed to determine their sessile drop advancing contact angles, in vitro. These studies indicated that poly-2-hydroxyethylmethacrylate (pHEMA)-based lenses are inherently more wettable than silicone-based lenses, unless they have a surface treatment that completely covers the hydrophobic siloxane groups. Additionally, certain combinations of lens materials and care regimens produce inherently more wettable surfaces when measured in vitro. <br /><br /> Suitable methods to assess contact lens wettability ex vivo, or after subjects had worn lenses for set periods of time, were developed. It was determined that using latex gloves to remove lenses had no impact upon the lens surface wettability and that rinsing of the lens surface after removal from the eye was required to determine the wettability of the underlying polymer. <br /><br /> The final wettability studies involved an analysis of various lens materials from clinical studies conducted within the Centre for Contact Lens Research (CCLR). These studies investigated differences in wettability between silicone hydrogel lenses manufactured from differing polymers and variations in ex vivo wettability of several combinations of lens materials and solutions, worn for varying periods of time. <br /><br /> A novel method to investigate proteins extracted from lenses using 2D-Difference in Gel Electrophoresis (DIGE) found that this technique could be used to analyze proteins extracted from contact lenses. The data obtained showed that there was no difference between a group of subjects who were symptomatic of lens-induced dryness or a control group, and that care solutions had a minimal influence on the pattern of deposition seen. <br /><br /> The overall conclusion of these studies is that hydrogel lens wettability is affected by the polymer composition and that care regimen components can modify the surface wettability.

The wettability of contact lenses has become an area of intense research, with the belief that the more "hydrophilic" or wettable the lens surface is, the more comfortable the lens may be, as the posterior surface of the eyelid will move more smoothly over it, hence increasing comfort. <br /><br /> There are many ways to assess the wettability of a given material, namely sessile drop,¹ captive bubble ² or Wilhelmy plate. ³ This thesis used the sessile drop method to determine the surface wettability of various hydrogel contact lens materials, by measuring the advancing contact angle made between the lens surface and a pre-determined volume of HPLC-grade water. This was followed by measuring the surface wettability following periods in which the lens materials were soaked in various contact lens care regimens. Further studies determined wettability of lens materials after various periods of in-eye wear and finally a study was undertaken to evaluate if a novel biological technique could be used to differentiate proteins that deposit on hydrogel lens materials that may affect wettability and cause discomfort. <br /><br /> A variety of hydrogel lenses, taken directly from their packaging and after soaking in various care regimens, were analyzed to determine their sessile drop advancing contact angles, in vitro. These studies indicated that poly-2-hydroxyethylmethacrylate (pHEMA)-based lenses are inherently more wettable than silicone-based lenses, unless they have a surface treatment that completely covers the hydrophobic siloxane groups. Additionally, certain combinations of lens materials and care regimens produce inherently more wettable surfaces when measured in vitro. <br /><br /> Suitable methods to assess contact lens wettability ex vivo, or after subjects had worn lenses for set periods of time, were developed. It was determined that using latex gloves to remove lenses had no impact upon the lens surface wettability and that rinsing of the lens surface after removal from the eye was required to determine the wettability of the underlying polymer. <br /><br /> The final wettability studies involved an analysis of various lens materials from clinical studies conducted within the Centre for Contact Lens Research (CCLR). These studies investigated differences in wettability between silicone hydrogel lenses manufactured from differing polymers and variations in ex vivo wettability of several combinations of lens materials and solutions, worn for varying periods of time. <br /><br /> A novel method to investigate proteins extracted from lenses using 2D-Difference in Gel Electrophoresis (DIGE) found that this technique could be used to analyze proteins extracted from contact lenses. The data obtained showed that there was no difference between a group of subjects who were symptomatic of lens-induced dryness or a control group, and that care solutions had a minimal influence on the pattern of deposition seen. <br /><br /> The overall conclusion of these studies is that hydrogel lens wettability is affected by the polymer composition and that care regimen components can modify the surface wettability.

<p>While eye drops are a well-accepted and convenient method for ocular drug delivery, they exhibit significant limitations such as poor drug bioavailability, low ocular residence time, pulsatile delivery profiles in the tear fluid as well as the need for patient compliance. Silicone hydrogel (SH) contact lenses have been proposed as alternative ocular drug delivery systems due to their potential for targeted delivery to the corneal surface and high oxygen permeability. The ability of novel hyaluronic acid (HA)-containing silicone hydrogel materials to release timolol maleate (TM), an antiglaucoma drug, or ketotifen fumarate (KF), an anti-histamine administered for ocular allergies, was examined.</p> <p>The releasable wetting and the therapeutic agent were added to the pre-polymer mixture of the SH during synthesis through direct entrapment, while the reaction was performed by UV induced free-radical. The impact of the wetting agent on the swellability, surface wettability, optical transparency and <em>in vitro </em>drug release was studied.</p> <p>Simultaneous drug and wetting agent incorporation resulted in modified SH materials with slightly increased water content and significantly improved surface wettability. In addition, the optical transparency of these materials was not affected by drug loading. However, direct entrapment of HA decreased their optical clarity. <em>In vitro</em> release showed that TM was released over a 14 day period, whereas KF release lasted up to 36 days. For both therapeutic agents used in the current research, non-covalent entrapment of wetting agent and its MW did not significantly change the release kinetics, however the release rate of TM was slowed and controlled by the release of the HA, due to electrostatic interactions between the protonated TM and the anionic HA.</p> <p>The development of SH materials capable of simultaneously releasing a therapeutic and a wetting agent for an extended period of time and in a sustained manner can have a significant potential as extended drug delivery systems for the treatment of front of the eye diseases while also possibly providing comfort during wear.</p> / Master of Applied Science (MASc)