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Over 60 proteins have been detected in the tear film and among these lysozyme has attracted the greatest attention. Several techniques for elucidating the identity, quantity and conformation of lysozyme deposited on soft contact lenses have been developed. Lysozyme also deposits on the newly introduced silicone hydrogel (SH) lens materials, but in extremely low levels compared to conventional hydrogel lenses. Hence, a major analytical complication with the study of the SH contact lens materials relates to the minute quantity of deposited lysozyme. The first project of this thesis involved the development of a method whereby lysozyme mass extracted from SH lens materials would be preserved over time and would be compatible with an optimized Western blotting procedure. This methodological development was incorporated into a clinical study (CLENS-100?? and Silicone Hydrogels ? CLASH study) wherein the difference in the degree of total protein, the difference in lysozyme deposition and activity recovered from lotrafilcon A SH lens material when subjects used surfactant containing rewetting drops (CLENS-100??) versus control saline was investigated. The remaining experiments were in vitro experiments wherein the lenses were doped in artificial lysozyme solution containing ¹²⁵I-labeled lysozyme. These experiments were performed to gain insight into the kinetics of lysozyme deposition on SH lens materials and also the efficacy of a reagent in extracting lysozyme from SH lens materials. A protocol was developed whereby the percentage loss of lysozyme mass found on lotrafilcon A SH lenses was reduced from approximately 33% to <1% (p<0. 001), following extraction and resuspension. The results from the CLASH study demonstrated that when subjects used a surfactant containing rewetting drop instead of a control saline drop total protein deposition (1. 2??0. 7 ??g/lens versus 1. 9??0. 8 ??g/lens, p<0. 001), lysozyme deposition (0. 7??0. 5 ??g/lens versus 1. 1??0. 7 ??g/lens, p<0. 001) and percentage lysozyme denaturation (76??10% versus 85??7%, p=0. 002) were all reduced. The results from the kinetics study demonstrated that lysozyme accumulated rapidly on etafilcon A lenses (1 hr, 98??8 ??g/lens), reached a maximum on the 7th day (1386??21 ??g/lens) and then reached a plateau (p=NS). Lysozyme accumulation on FDA Group II and SH lenses continued to increase across all time periods, with no plateau being observed (p<0. 001). The results from the extraction efficiency study showed that 0. 2% trifluoroacetic acid/ acetonitrile was 98. 3??1. 1% and 91. 4??1. 4% efficient in extracting lysozyme deposited on etafilcon A and galyfilcon lenses, while the lysozyme extraction efficiency was 66. 3??5. 3 % and 56. 7??3. 8% for lotrafilcon A and balafilcon lens materials (p<0. 001). The results from these studies re-emphasize that novel SH lens materials are highly resistant to protein deposition and demonstrate high levels of biocompatibility.

The primary objective of this study was to quantify and characterise lipid deposition on soft (hydrogel) contact lenses, particularly those containing siloxane components. Studies involving a variety of <em>in vitro</em> doping and <em>in vivo</em> worn contact lenses were undertaken, in which lipid deposition was analyzed by either TLC or HPLC. Specific experiments were completed to optimize a method to extract the lipid from the lens materials, to compare the total lipid deposition on nine different hydrogel lenses and to analyze the effect that lipid deposition had on wettability. A method for extracting lipid from contact lenses using 2:1 chloroform: methanol was developed. This study also showed that siloxane-containing contact lens materials differ in the degree to which they deposit lipid, which is dependent upon their chemical composition. Small differences in lipid deposition that occur due to using variations in cleaning regimens were not identifiable through TLC, and required more sophisticated analysis using HPLC. Contact lens material wettability was found to be influenced by <em>in vitro</em> lipid deposition. Specifically, conventional hydrogels and plasma surface-treated silicone-hydrogel materials experienced enhanced wettability with lipid deposition. Reverse-phase HPLC techniques were able to quantify lipid deposits with increased sensitivity and accuracy. From the HPLC studies it was found that contact lens material, concentration of the lipid doping solution, and the composition of the lipid doping solution in <em>in vitro</em> deposition studies influenced the ultimate amount and composition of lipid deposits. <em>In vivo</em> HPLC studies showed that the final lipid deposition pattern was influenced by the interaction between the composition of the tear film and the various silicone hydrogel contact lens materials. In conclusion, HPLC analysis methods were more sensitive and quantitative than TLC. Lipid deposition was ultimately influenced by the concentration and composition of the lipid in the tear film and the contact lens material. Contact lens wettability was influenced by the presence and deposition of lipid onto the contact lens surfaces. Finally, this reverse-phase HPLC lipid analysis protocol was not the most sensitive, robust, or accurate. In the future, other methods of analysis should be explored.

Introduction Contact lenses suffer from the same problems of deposition that other biomaterials exhibit, being rapidly coated with a variety of proteins, lipids and mucins. The first event observed at the interface between a contact lens and tear fluid is protein adsorption. Protein deposits on contact lenses are associated with diminished visual acuity, dryness and discomfort and lid-related inflammatory changes. The aim of this thesis was to determine the quantity and the conformational state of lysozyme deposited on contact lens materials over various time periods and also to determine the clinical relevance of protein deposits on contact lenses. The specific aims of each chapter of this thesis were as follows: • Chapter 4: To determine the total lysozyme deposition on conventional and silicone hydrogel contact lens materials as a function of time by artificially doping lenses with 125I-labeled lysozyme. • Chapter 5: To determine the conformational state of lysozyme deposited on conventional and silicone hydrogel contact lens materials as a function of time using an in vitro model. • Chapter 6: To quantify the total protein, total lysozyme and the conformational state of lysozyme deposited on a novel, lathe-cut silicone hydrogel contact lens material after three-months of wear. • Chapter 7: To determine the relationship between protein deposition and clinical signs & symptoms after one-day wear of etafilcon lenses in a group of symptomatic and asymptomatic lens wearers. • Chapter 8: To determine the influence of individual tear proteins (lysozyme, lactoferrin and albumin) on the adhesion of Gram positive and Gram negative bacteria to conventional and silicone hydrogel contact lens materials. Methods • Chapter 4: Conventional hydrogel FDA group I (polymacon), group II (alphafilcon A and omafilcon A), group IV (etafilcon A and vifilcon A), polymethyl methacrylate and silicone hydrogel lens materials (lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A and senofilcon A) were incubated in a lysozyme solution containing 125I-labeled lysozyme for time periods ranging from 1 hour to 28 days. After each time period, lysozyme deposited on contact lens materials was determined using a Gamma Counter. • Chapter 5: Conventional hydrogel FDA groups I, II, IV and silicone hydrogel lens materials were incubated in lysozyme solution for time periods ranging from 1 hour to 28 days. After each time period, the lysozyme deposited on the lenses was extracted and the sample extracts were assessed for lysozyme activity and total lysozyme. • Chapter 6: 24 subjects completed a prospective, bilateral, daily-wear, nine month clinical evaluation in which the subjects were fitted with a novel, custom-made, lathe-cut silicone hydrogel lens material (sifilcon A). After 3 months of wear, the lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 7: 30 adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon lenses. Objective measures and subjective symptoms were assessed at baseline and after hours 2, 4, 6 and 8. After 2, 4, 6 and 8 hour time points, lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 8: Three silicone hydrogel (balafilcon A, lotrafilcon B & senofilcon A) and one conventional hydrogel (etafilcon A) lens materials were coated with lysozyme, lactoferrin and albumin. Uncoated and protein-coated contact lens samples were incubated in a bacterial suspension of Staphylococcus aureus 31 and two strains of Pseudomonas aeruginosa (6294 & 6206). The total counts and the viable counts of the adhered bacteria were assayed. Results • Chapter 4: Lysozyme accumulated rapidly on conventional hydrogel FDA group IV lenses, reached a maximum on day 7 and then plateaued with no further increase. PMMA showed a deposition pattern similar to that seen on lotrafilcon A and lotrafilcon B silicone hydrogel lenses. After 28 days, conventional hydrogel FDA group IV lenses deposited the most lysozyme. • Chapter 5: After 28 days, lysozyme deposited on group IV lenses exhibited the greatest activity. Lysozyme deposited on polymacon, lotrafilcon A and lotrafilcon B exhibited the lowest activity. Lysozyme deposited on omafilcon, galyfilcon, senofilcon, and balafilcon exhibited intermediate activity. • Chapter 6: The total protein recovered from the custom-made lenses was 5.3±2.3 µg/lens and the total lysozyme was 2.4±1.2 µg/lens. The denatured lysozyme found on the lenses was 1.9±1.0 µg/lens and the percentage of lysozyme denatured was 80±10%. • Chapter 7: Correlations between subjective symptoms and protein deposition showed poor correlations for total protein/ lysozyme and any subjective factor, and only weak correlations between dryness and active lysozyme. However, stronger correlations were found between active lysozyme and subjective comfort. • Chapter 8: Different tear proteins had varying effects on the adhesion of bacteria to contact lens materials. Lysozyme deposits on contact lenses increased the adhesion of Gram positive Staphyloccocus aureus 31 strain, while albumin deposits increased the adhesion of both the Gram positive Staphyloccocus aureus and Gram negative Pseudomonas aeruginosa 6206 & 6294 strains. Lactoferrin deposits increased the total counts of both the Gram positive and Gram negative strains, while they reduce the viable counts of the Gram negative strains. Conclusions • Chapter 4: Lysozyme deposition is driven by both the bulk chemistry and also the surface properties of conventional and silicone hydrogel contact lens materials. The surface modification processes or surface-active monomers on silicone hydrogel lens materials also play a significant role in lysozyme deposition. • Chapter 5: The reduction in the activity of lysozyme deposited on contact lens materials is time dependent and the rate of reduction varies between lens materials. This variation in activity recovered from lenses could be due to the differences in surface/ bulk material properties or the location of lysozyme on these lenses. • Chapter 6: Even after three-months of wear, the quantity of protein and the conformational state of lysozyme deposited on these novel lens materials was very similar to that found on similar surface-coated silicone hydrogel lenses after two to four weeks of wear. These results indicate that extended use of the sifilcon A material is not deleterious in terms of the quantity and quality of protein deposited on the lens. • Chapter 7: In addition to investigating the total protein deposited on contact lenses, it is of significant clinical relevance to determine the conformational state of the deposited protein. • Chapter 8: Uncoated silicone hydrogel lens materials bind more Gram positive and Gram negative bacteria than uncoated conventional hydrogel lens materials. Lysozyme deposited on contact lens materials does not possess antibacterial activity against all bacterial strains tested, while lactoferrin possess an antibacterial effect against certain Gram negative strains tested in this study. This thesis has provided hitherto unavailable information on contact lens deposition and its influence on subjective symptoms and bacterial binding. These results suggest that protein deposition has a significant potential to cause problems. Therefore, it is important that practitioners advise their patients regarding the importance of lens disinfection and cleaning and appropriate lens replacement schedules. These results will also be useful for the contact lens industry and the general field of biomaterials research.

Over 60 proteins have been detected in the tear film and among these lysozyme has attracted the greatest attention. Several techniques for elucidating the identity, quantity and conformation of lysozyme deposited on soft contact lenses have been developed. Lysozyme also deposits on the newly introduced silicone hydrogel (SH) lens materials, but in extremely low levels compared to conventional hydrogel lenses. Hence, a major analytical complication with the study of the SH contact lens materials relates to the minute quantity of deposited lysozyme. The first project of this thesis involved the development of a method whereby lysozyme mass extracted from SH lens materials would be preserved over time and would be compatible with an optimized Western blotting procedure. This methodological development was incorporated into a clinical study (CLENS-100® and Silicone Hydrogels ? CLASH study) wherein the difference in the degree of total protein, the difference in lysozyme deposition and activity recovered from lotrafilcon A SH lens material when subjects used surfactant containing rewetting drops (CLENS-100®) versus control saline was investigated. The remaining experiments were in vitro experiments wherein the lenses were doped in artificial lysozyme solution containing ¹²⁵I-labeled lysozyme. These experiments were performed to gain insight into the kinetics of lysozyme deposition on SH lens materials and also the efficacy of a reagent in extracting lysozyme from SH lens materials. A protocol was developed whereby the percentage loss of lysozyme mass found on lotrafilcon A SH lenses was reduced from approximately 33% to <1% (p<0. 001), following extraction and resuspension. The results from the CLASH study demonstrated that when subjects used a surfactant containing rewetting drop instead of a control saline drop total protein deposition (1. 2±0. 7 µg/lens versus 1. 9±0. 8 µg/lens, p<0. 001), lysozyme deposition (0. 7±0. 5 µg/lens versus 1. 1±0. 7 µg/lens, p<0. 001) and percentage lysozyme denaturation (76±10% versus 85±7%, p=0. 002) were all reduced. The results from the kinetics study demonstrated that lysozyme accumulated rapidly on etafilcon A lenses (1 hr, 98±8 µg/lens), reached a maximum on the 7th day (1386±21 µg/lens) and then reached a plateau (p=NS). Lysozyme accumulation on FDA Group II and SH lenses continued to increase across all time periods, with no plateau being observed (p<0. 001). The results from the extraction efficiency study showed that 0. 2% trifluoroacetic acid/ acetonitrile was 98. 3±1. 1% and 91. 4±1. 4% efficient in extracting lysozyme deposited on etafilcon A and galyfilcon lenses, while the lysozyme extraction efficiency was 66. 3±5. 3 % and 56. 7±3. 8% for lotrafilcon A and balafilcon lens materials (p<0. 001). The results from these studies re-emphasize that novel SH lens materials are highly resistant to protein deposition and demonstrate high levels of biocompatibility.

The primary objective of this study was to quantify and characterise lipid deposition on soft (hydrogel) contact lenses, particularly those containing siloxane components. Studies involving a variety of <em>in vitro</em> doping and <em>in vivo</em> worn contact lenses were undertaken, in which lipid deposition was analyzed by either TLC or HPLC. Specific experiments were completed to optimize a method to extract the lipid from the lens materials, to compare the total lipid deposition on nine different hydrogel lenses and to analyze the effect that lipid deposition had on wettability. A method for extracting lipid from contact lenses using 2:1 chloroform: methanol was developed. This study also showed that siloxane-containing contact lens materials differ in the degree to which they deposit lipid, which is dependent upon their chemical composition. Small differences in lipid deposition that occur due to using variations in cleaning regimens were not identifiable through TLC, and required more sophisticated analysis using HPLC. Contact lens material wettability was found to be influenced by <em>in vitro</em> lipid deposition. Specifically, conventional hydrogels and plasma surface-treated silicone-hydrogel materials experienced enhanced wettability with lipid deposition. Reverse-phase HPLC techniques were able to quantify lipid deposits with increased sensitivity and accuracy. From the HPLC studies it was found that contact lens material, concentration of the lipid doping solution, and the composition of the lipid doping solution in <em>in vitro</em> deposition studies influenced the ultimate amount and composition of lipid deposits. <em>In vivo</em> HPLC studies showed that the final lipid deposition pattern was influenced by the interaction between the composition of the tear film and the various silicone hydrogel contact lens materials. In conclusion, HPLC analysis methods were more sensitive and quantitative than TLC. Lipid deposition was ultimately influenced by the concentration and composition of the lipid in the tear film and the contact lens material. Contact lens wettability was influenced by the presence and deposition of lipid onto the contact lens surfaces. Finally, this reverse-phase HPLC lipid analysis protocol was not the most sensitive, robust, or accurate. In the future, other methods of analysis should be explored.

Introduction Contact lenses suffer from the same problems of deposition that other biomaterials exhibit, being rapidly coated with a variety of proteins, lipids and mucins. The first event observed at the interface between a contact lens and tear fluid is protein adsorption. Protein deposits on contact lenses are associated with diminished visual acuity, dryness and discomfort and lid-related inflammatory changes. The aim of this thesis was to determine the quantity and the conformational state of lysozyme deposited on contact lens materials over various time periods and also to determine the clinical relevance of protein deposits on contact lenses. The specific aims of each chapter of this thesis were as follows: • Chapter 4: To determine the total lysozyme deposition on conventional and silicone hydrogel contact lens materials as a function of time by artificially doping lenses with 125I-labeled lysozyme. • Chapter 5: To determine the conformational state of lysozyme deposited on conventional and silicone hydrogel contact lens materials as a function of time using an in vitro model. • Chapter 6: To quantify the total protein, total lysozyme and the conformational state of lysozyme deposited on a novel, lathe-cut silicone hydrogel contact lens material after three-months of wear. • Chapter 7: To determine the relationship between protein deposition and clinical signs & symptoms after one-day wear of etafilcon lenses in a group of symptomatic and asymptomatic lens wearers. • Chapter 8: To determine the influence of individual tear proteins (lysozyme, lactoferrin and albumin) on the adhesion of Gram positive and Gram negative bacteria to conventional and silicone hydrogel contact lens materials. Methods • Chapter 4: Conventional hydrogel FDA group I (polymacon), group II (alphafilcon A and omafilcon A), group IV (etafilcon A and vifilcon A), polymethyl methacrylate and silicone hydrogel lens materials (lotrafilcon A, lotrafilcon B, balafilcon A, galyfilcon A and senofilcon A) were incubated in a lysozyme solution containing 125I-labeled lysozyme for time periods ranging from 1 hour to 28 days. After each time period, lysozyme deposited on contact lens materials was determined using a Gamma Counter. • Chapter 5: Conventional hydrogel FDA groups I, II, IV and silicone hydrogel lens materials were incubated in lysozyme solution for time periods ranging from 1 hour to 28 days. After each time period, the lysozyme deposited on the lenses was extracted and the sample extracts were assessed for lysozyme activity and total lysozyme. • Chapter 6: 24 subjects completed a prospective, bilateral, daily-wear, nine month clinical evaluation in which the subjects were fitted with a novel, custom-made, lathe-cut silicone hydrogel lens material (sifilcon A). After 3 months of wear, the lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 7: 30 adapted soft contact lens wearers (16 symptomatic and 14 asymptomatic) were fitted with etafilcon lenses. Objective measures and subjective symptoms were assessed at baseline and after hours 2, 4, 6 and 8. After 2, 4, 6 and 8 hour time points, lenses were collected and total protein, total lysozyme and active lysozyme deposition were assessed. • Chapter 8: Three silicone hydrogel (balafilcon A, lotrafilcon B & senofilcon A) and one conventional hydrogel (etafilcon A) lens materials were coated with lysozyme, lactoferrin and albumin. Uncoated and protein-coated contact lens samples were incubated in a bacterial suspension of Staphylococcus aureus 31 and two strains of Pseudomonas aeruginosa (6294 & 6206). The total counts and the viable counts of the adhered bacteria were assayed. Results • Chapter 4: Lysozyme accumulated rapidly on conventional hydrogel FDA group IV lenses, reached a maximum on day 7 and then plateaued with no further increase. PMMA showed a deposition pattern similar to that seen on lotrafilcon A and lotrafilcon B silicone hydrogel lenses. After 28 days, conventional hydrogel FDA group IV lenses deposited the most lysozyme. • Chapter 5: After 28 days, lysozyme deposited on group IV lenses exhibited the greatest activity. Lysozyme deposited on polymacon, lotrafilcon A and lotrafilcon B exhibited the lowest activity. Lysozyme deposited on omafilcon, galyfilcon, senofilcon, and balafilcon exhibited intermediate activity. • Chapter 6: The total protein recovered from the custom-made lenses was 5.3±2.3 µg/lens and the total lysozyme was 2.4±1.2 µg/lens. The denatured lysozyme found on the lenses was 1.9±1.0 µg/lens and the percentage of lysozyme denatured was 80±10%. • Chapter 7: Correlations between subjective symptoms and protein deposition showed poor correlations for total protein/ lysozyme and any subjective factor, and only weak correlations between dryness and active lysozyme. However, stronger correlations were found between active lysozyme and subjective comfort. • Chapter 8: Different tear proteins had varying effects on the adhesion of bacteria to contact lens materials. Lysozyme deposits on contact lenses increased the adhesion of Gram positive Staphyloccocus aureus 31 strain, while albumin deposits increased the adhesion of both the Gram positive Staphyloccocus aureus and Gram negative Pseudomonas aeruginosa 6206 & 6294 strains. Lactoferrin deposits increased the total counts of both the Gram positive and Gram negative strains, while they reduce the viable counts of the Gram negative strains. Conclusions • Chapter 4: Lysozyme deposition is driven by both the bulk chemistry and also the surface properties of conventional and silicone hydrogel contact lens materials. The surface modification processes or surface-active monomers on silicone hydrogel lens materials also play a significant role in lysozyme deposition. • Chapter 5: The reduction in the activity of lysozyme deposited on contact lens materials is time dependent and the rate of reduction varies between lens materials. This variation in activity recovered from lenses could be due to the differences in surface/ bulk material properties or the location of lysozyme on these lenses. • Chapter 6: Even after three-months of wear, the quantity of protein and the conformational state of lysozyme deposited on these novel lens materials was very similar to that found on similar surface-coated silicone hydrogel lenses after two to four weeks of wear. These results indicate that extended use of the sifilcon A material is not deleterious in terms of the quantity and quality of protein deposited on the lens. • Chapter 7: In addition to investigating the total protein deposited on contact lenses, it is of significant clinical relevance to determine the conformational state of the deposited protein. • Chapter 8: Uncoated silicone hydrogel lens materials bind more Gram positive and Gram negative bacteria than uncoated conventional hydrogel lens materials. Lysozyme deposited on contact lens materials does not possess antibacterial activity against all bacterial strains tested, while lactoferrin possess an antibacterial effect against certain Gram negative strains tested in this study. This thesis has provided hitherto unavailable information on contact lens deposition and its influence on subjective symptoms and bacterial binding. These results suggest that protein deposition has a significant potential to cause problems. Therefore, it is important that practitioners advise their patients regarding the importance of lens disinfection and cleaning and appropriate lens replacement schedules. These results will also be useful for the contact lens industry and the general field of biomaterials research.

The challenge of demolding during the cast molding process of silicone hydrogel contact lenses can be addressed with the application of hydrophobic coatings on the surface of lens mold. In particular, the adhesion between silicone hydrogel and silicate substrates was minimized by applying silane modification on the surface of silicate substrates. Peel tests were conducted to measure the adhesive strengths between silicone hydrogel and surface modified glass substrates. Water contact angle measurement and X-ray photoelectron spectroscopy (XPS) were utilized to characterize the surface properties of silane treated glass substrates.Silicone hydrogel was obtained by curing macromer mixture under UV for 6 minutes, with UV intensity of 95.0 mW/cm2. The obtained silicone hydrogel had a modulus of 0.87±0.09 MPa, within the same range of commercial contact lenses. And the hydrogel with a UV curing time of 6 minutes was unable to be peeled off from clean glass substrates. The effects of silane type and concentration on coating effectiveness were investigated and the most effective types of silane were found to be triethoxyphenylsilane (TEPhS) and octyltriethoxysilane (OTES), with an optimal concentration of 5 wt%. The peel strength between silicone hydrogel and silicate substrates was reduced to below 15.5 N/m with the application of TEPhS and OTES coatings. However, these silane coatings were not durable enough. Silane coupling agents need to be reapplied before each curing process of silicone hydrogel. / Thesis / Master of Applied Science (MASc)

Polymeric biomaterials have created significant advances in the field of biomedical engineering, however, very few polymeric drug delivery devices have achieved clinical and commercial success. Thus, the motivation for this thesis was to encourage long-term success of materials through expanding the fundamental understanding of polymer properties. Poly(ethylene glycol) was specifically chosen for study as its polyether backbone provides it with many unique properties that are still not fully understood, and are not seen with other similar polymers. PEG has been shown to exhibit amphiphilic character, due to its high conformational freedom, and the ability to hydrogen-bond 2-3 water molecules for each ethylene oxide subunit, creating a very structured water shell and large hydrodynamic radius. Together, the properties formed the hypothesis for the possibility for PEG to control drug release and its environment, expanding its potential in biomedical applications. This hypothesis was investigated with PEG in three states – free PEG, conjugated and blended. Free PEG was determined to inhibit melanoma cell viability by activating apoptosis via PEG effects on the osmolality of the cell medium (Chapter 3). Novel silicone hydrogels incorporating methacrylated PEG as the sole hydrophilic component showed advantageous properties for biomedical applications across a range of formulations (such as low contact angle and protein deposition), as well as altering the release of highly hydrophilic antibiotics from the materials, presumably via PEG-drug hydrogen bonding (Chapter 4). Novel siloxane-PEG blended materials were shown to have the ability to influence drug release of hydrophilic, hydrophobic and drug salts through the structure of PEG (Chapter 5). Overall, the work within this thesis expanded understanding of the abilities and limitations of PEG based on its distinct structure, and expanded the potential for PEG in biomedical applications to more than being used as simply a hydrophilic additive. / Thesis / Doctor of Philosophy (PhD) / Polymeric biomaterials have created significant advances in the field of biomedical engineering, however, very few polymeric drug delivery devices have achieved clinical and commercial success. Thus, the motivation for this thesis was to encourage long-term success of materials through expanding the fundamental understanding of polymer properties. Poly(ethylene glycol) was specifically chosen for study due to its unique exhibition of amphiphilic character and the ability to hydrogen-bond multiple water molecules, that together suggest the possibility for PEG to control drug release and its environment. Through strategic experimental designs, greater understanding of the abilities and limitations of PEG was established and shown to be the result of the distinct structure of PEG. Specifically, two novel drug delivery systems were developed with demonstrated understanding of the structure-function relationship between polymers and drugs, and the activity of PEG as a melanoma cell viability inhibitor was discovered and found correlated to the PEG structure. Overall the work within this thesis expanded the potential for PEG in biomedical applications to more than being used as simply a hydrophilic additive.

Currently, most contact lenses are made with a silicone hydrogel (Si-Hy) blend that provides softness for comfort as well as high oxygen permeability. Silicone hydrogel lenses have both hydrophilic and hydrophobic areas, and the natural hydrophobicity of the material contributes to biofouling, which is the adsorption of proteins and lipids from the tear film of the eye. Published in vitro investigations into the quantity and spatial distribution of lipids deposited on contact lenses usually involve the use of artificial tear fluid (ATF) that is not changed or replenished over the course of the experiments. Yet, the natural tear film is constantly replenished by the meibomian and lacrimal glands. The intent of this study was to investigate the significance of replenishing the ATF over the study period on lipid absorption profiles and quantities. In part one, fluorescence confocal microscopy was used to observe the penetration profiles of lipids into nine different Si-Hy lenses. In part two, radiolabeling was used to quantify the amount of lipid absorbed by nine different Si-Hy lenses. Using a non-static exposure method was found to allow more absorption of cholesterol than the static method. The non-static method also provided more differentiation between lens types and brands in lipid absorption profiles and amounts than the static method. / acase@tulane.edu