Impact of Air Exposure Time on the Water Contact Angles of Daily Disposable Silicone Hydrogels.

The wettability of silicone hydrogel (SiHy) contact lens (CLs) is crucial for the pre-lens tear film stability throughout the day. Therefore, sessile drop and captive bubble setups were used to study the advancing and receding water contact angles (CA) of four SiHy materials: narafilcon A (TE), senofilcon A (AOD), stenfilcon A (MD), and delefilcon A (DT). TE and AOD have 48% and 38% water content, respectively, and no surface coating. MD (54% water) implements "smart chemistry" with just 4.4% bulk silicone content, while DT has >80% water at its surface. These SiHy were subjected to continuous blink-like air exposure (10 s)/rehydration (1s) cycles for 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, and 16 h. The advancing CA, which measures the rehydration propensity of the CL surface, proved to be the most sensitive parameter to discriminate between the samples. The order of performance for the entire time scale was DT > MD >> AOD ≥ TE. The extended desiccation/rehydration cycling increased the differences between the CA of DT and MD compared to AOD and TE. This suggests that the low Si surface content and the high surface hydration are major determinants of SiHy wettability.

Contact lens to measure individual ion concentrations in tears and applications to dry eye disease.

Dry eye disease (DED) affects millions of individuals in the United States and worldwide, and the incidence is increasing with an aging population. There is widespread agreement that the measurement of total tear osmolarity is the most reliable test, but this procedure provides only the total ionic strength and does not provide the concentration of each ionic species in tears. Here, we describe an approach to determine the individual ion concentrations in tears using modern silicone hydrogel (SiHG) contact lenses. We made pH (or H3O+, hydronium cation,/OH-, hydroxyl ion) and chloride ion (two of the important electrolytes in tear fluid) sensitive SiHG contact lenses. We attached hydrophobic C18 chains to water-soluble fluorescent probes for pH and chloride. The resulting hydrophobic ion sensitive fluorophores (H-ISF) bind strongly to SiHG lenses and could not be washed out with aqueous solutions. Both H-ISFs provide measurements which are independent of total intensity by use of wavelength-ratiometric measurements for pH or lifetime-based sensing for chloride. Our approach can be extended to fabricate a contact lens which provides measurements of the six dominant ionic species in tears. This capability will be valuable for research into the biochemical processes causing DED, which may improve the ability to diagnose the various types of DED.

Enhanced plasmid loss in bacterial populations exposed to the antimicrobial compound irgasan delivered from interpenetrating polymer network silicone hydrogels.

The spread of antimicrobial resistance, usually mediated by horizontal transfer of plasmids, limits the options of treating bacterial infections and thereby poses a crucial human health problem. The disturbance of plasmid stability within bacterial species in clinical environments serves as a novel strategy to reduce the development and dissemination of antibiotic resistance. We tested the ability of irgasan to destabilize plasmids from Escherichia coli K-12 cells when added directly into liquid growth medium at concentrations below levels of marked bacterial growth inhibition, or when released into liquid growth medium from irgasan-impregnated Interpenetrating Polymer Network (IPN) silicone hydrogel objects, a novel technology developed as drug-delivery platform. IPN-mediated irgasan-release was indirectly monitored as the extent of plasmid loss from bacterial cells during a 24-hour period or during repeated exposure to new irgasan-loaded IPN devices every 24h for a total of 10days. The cells were genetically modified so that plasmid loss could be quantified by applying a combination of fluorescence-based reporter gene technology and flow cytometry. When exposing bacterial cells to the irgasan-impregnated IPNs for 24h, we observed a modest (2.8-4.7%), but significant (P<0.05), plasmid loss as well as an inhibition of bacterial growth, both gradually increasing with increasing impregnation concentration. Repeated exposure to irgasan-impregnated IPNs drastically increased the plasmid loss of up to 83%, but cells adapted over time, which indicated the limitations of this specific drug for future medical applications. This study, however, illustrates the ability of IPNs to release an impregnated compound into a liquid suspension to induce a significant biological impact on growing bacterial cells.

Inorganic-Organic Interpenetrating Network Hydrogels as Tissue-Integrating Luminescent Implants: Physicochemical Characterization and Preclinical Evaluation.

Sensors capable of accurate, continuous monitoring of biochemistry are crucial to the realization of personalized medicine on a large scale. Great strides have been made to enhance tissue compatibility of long-term in vivo biosensors using biomaterials strategies such as tissue-integrating hydrogels. However, the low level of oxygen in tissue presents a challenge for implanted devices, especially when the biosensing function relies on oxygen as a measure-either as a primary analyte or as an indirect marker to transduce levels of other biomolecules. This work presents a method of fabricating inorganic-organic interpenetrating network (IPN) hydrogels to optimize the oxygen transport through injectable biosensors. Capitalizing on the synergy between the two networks, various physicochemical properties (e.g., swelling, glass transition temperature, and mechanical properties) are shown to be independently adjustable while maintaining a 250% increase in oxygen permeability relative to poly(2-hydroxyethyl methacrylate) controls. Finally, these gels, when functionalized with a Pd(II) benzoporphyrin phosphor, track tissue oxygen in real time for 76 days as subcutaneous implants in a porcine model while promoting tissue ingrowth and minimizing fibrosis around the implant. These findings support IPN networks for fine-tuned design of implantable biomaterials in personalized medicine and other biomedical applications.

In vitro affinity for nicotine of soft contact lenses of different materials.

Smoking is a risk factor for the development of microbial keratitis and corneal infiltrates in contact lens (CL) wearers. It is still unknown if this risk is directly associated with the presence of nicotine in the eye and if adherence of nicotine on the CL can enhance these effects. A better understanding of the interaction between nicotine and CL materials could offer insights to explain this risk associated with smoking. The aim of this work was to compare the affinity of nicotine to different soft CL materials. CLs from FDA groups I, II, IV, and V were incubated in a 2-mM nicotine solution for 24 h and then in a 0.9% saline solution for the next 24 h. The amount of absorbed and released nicotine per CL was deduced as a function of time (t) by ultraviolet (UV) spectrophotometry and normalised to the mass of the hydrated CL. The data were described by the equation y = b -a t-1, where a and b are constants, and b represents the mass reached at the plateau after ~ 10 min of exposure. Groups IV and V displayed the highest (0.80 ± 0.09 µg) and lowest (0.27 ± 0.08 µg) nicotine absorption per mg of hydrated CL, respectively. The CL affinity for nicotine could be ascribed to the interaction between the positive charge of nicotine pyrrolidine nitrogen and the negative charges of the CLs, especially for the ionic IV group.

The influence of structure and morphology on ion permeation in commercial silicone hydrogel contact lenses.

The importance of the microstzructure of silicone hydrogels is widely appreciated but is poorly understood and minimally investigated. To ensure comfort and eye health, these materials must simultaneously exhibit both high oxygen and high water permeability. In contrast with most conventional hydrogels, the water content and water structuring within silicone hydrogels cannot be solely used to predict permeability. The materials achieve these opposing requirements based on a composite of nanoscale domains of oxygen-permeable (silicone) and water-permeable hydrophilic components. This study correlated characteristic ion permeation coefficients of a selection of commercially available silicone hydrogel contact lenses with their morphological structure and chemical composition. Differential scanning calorimetry measured the water structuring properties through subdivision of the freezing water component into polymer-associated water (loosely bound to the polymer matrix) and ice-like water (unimpeded with a melting point close to that of pure water). Small-angle x-ray scattering, and environmental scanning electron microscopy techniques were used to investigate the structural morphology of the materials over a range of length scales. Significant, and previously unrecognized, differences in morphology between individual materials at nanometer length scales were determined; this will aid the design and performance of the next generation of ocular biomaterials, capable of maintaining ocular homeostasis.

Relationships between the material properties of silicone hydrogels: Desiccation, wettability and lubricity.

Silicone hydrogels (SiHy), represent composite matrices composed of hydrophobic gas permeable silicone (Si) rich core and a surface enriched with hydrophilic polymer moieties. Their utilization in contact lens design requires number of SiHy properties (hydration, wettability, lubricity) to be optimized for the challenging conditions at the ocular surface. Typical limitations in literature are that (i) these properties are studied in isolation, monitoring only one parameter but not the rest of them, and (ii) measurements are performed with hydrated samples immediately after removal from storage solutions. Here we study the simultaneous evolution of critical material properties (evaporative loss of water, water contact angle, coefficient of friction) of different SiHy subjected to continuous blink-like desiccation/rehydration cycling. SiHy with wetting agents incorporated in their core (narafilcon A, senofilcon A) were particularly susceptible to extended desiccation. Stenfilcon A, a material with only 3% bulk Si content maintained its performance for 4 h of cycling, and delefilcon A (80% surface water content) resisted extended 8 h of desiccation/rehydration runs. Strong correlation exists between the evolution of SiHy wettability and lubricity at ≥4 h of blink-like cycling. Understanding the interplay between SiHy properties bears insights for knowledge based design of novel ophthalmic materials.

Altering the release of tobramycin by incorporating poly(ethylene glycol) into model silicone hydrogel contact lens materials.

Delivery of drugs from contact lens materials is attractive for a number of reasons. However, the controlled delivery of hydrophilic drugs can be difficult to achieve due to the burst release of drug that is associated with materials of high water content, such as hydrogels. Silicone hydrogels have significant potential for drug delivery due to their increased hydrophobicity and the tortuous nature of the pores, overcoming some of the limitations associated with conventional hydrogel materials. The aim of this study was to examine the potential of model poly(ethylene glycol) (PEG) containing silicone hydrogels for delivery of hydrophilic aminoglycoside antibiotics. It was hypothesized that PEG, a polymer that has seen extensive use in biomedical applications, will provide in addition to hydrophilicity and protein repulsion, a mechanism for controlling the delivery of this hydrophilic antibiotic. PEG was combined with the macromer TRIS to create the model silicone hydrogel materials. The optical and physical properties of the novel TRIS-co-PEG silicone hydrogels exhibited excellent transparency, appropriate refractive index and high transmittance indicating minimal phase separation. Desirable properties such as wettability and protein repulsion were maintained across a wide range of formulations. The water content was found to be highly correlated with the ethylene oxide content. Drug release could be influenced through PEG content and was found to fit Higuchi-like kinetics. Overall, the study demonstrates that incorporation of PEG into a model silicone hydrogel could be used to control the release of a hydrophilic compound. Data suggests this is related to the unique structure and properties of PEG, which alter the types of water found in each formulation and the water content.

Epalrestat-loaded silicone hydrogels as contact lenses to address diabetic-eye complications.

Most treatments for diabetic eye conditions rely on systemic (oral) or intravitreal administration, and there is still a demand of efficient and comfortable ocular dosage forms. Our purpose was to design contact lenses (CLs) suitable for local prophylaxis/treatment of diabetes-related ocular pathologies, by means of the incorporation of bioinspired functional groups that can reversibly interact with epalrestat, an aldose reductase inhibitor. Several sets of silicone hydrogels were synthesized varying the contents in 2-hydroxyethyl methacrylate (HEMA), monomethacryloxypropyl-sym-polydimethylsiloxane hydroxypropyl terminated (MCS-MC12), and aminopropyl methacrylamide (APMA). Epalrestat was incorporated before or after polymerization, and loading and release profiles compared. All sets were evaluated regarding optical properties, oxygen permeability, swelling, cytocompatibility, ocular irritation, and corneal drug penetration (using a drug solution as reference). Designed silicone hydrogels showed adequate properties to be used as CLs. Affinity for epalrestat strongly depended on the content in APMA, which endowed the hydrogels with prolonged release in 0.9% NaCl for one week, both after synthesis and after being re-loaded. Bovine corneal permeability tests demonstrated that epalrestat released from the hydrogels can efficiently accumulate into the cornea in spite the concentrations provided on cornea surface were lower than those attained after instillation of concentrated eyedrops. Epalrestat-loaded hydrogels also demonstrated anti-cataract activity in an in vitro model of diabetic eye. Overall, silicone hydrogel CLs functionalized with bioinspired chemical groups represent a first attempt to design CLs adapted to the needs of diabetic eyes, acting as controlled release platforms of epalrestat, promoting drug accumulation and diffusion through cornea.

Sagittal height differences of frequent replacement silicone hydrogel contact lenses.

PURPOSE: This study aims to evaluate the sagittal height differences among a selection of commercially available monthly or two weekly replacement silicone hydrogel soft lenses. METHODS: The sagittal height (CL-SAG) of four frequent replacement silicone hydrogel lenses (lotrafilcon B, balafilcon A, comfilcon A and senofilcon A) was measured for all base curve radius manufactured in spherical (-3.00D and +3.00D) and toric (=C-0.75×180°) designs (11 spherical and 8 toric lenses in total). Two different lenses of each lens type were evaluated (the intra CL-SAG) using the SHSOphthalmic omniSpect by Optocraft. RESULTS: The intra CL-SAG difference (the difference between two identical lenses from the same batch) was 11±SD 2µm. The CL-SAG of all minus lenses ranged from 3454 to 3765µm (an inter CL-SAG difference of 311µm), while the plus spherical lenses ranged from 3493 to 3757µm (inter CL-SAG difference 264µm). In the toric lens group, the range in toric minus lenses was 3495-3953µm (inter CL-SAG difference 458µm) and 3493-3980µm in the plus group (inter CL-SAG difference 487µm). The inter CL-SAG difference between the spherical and the toric lenses was statistically significant (p=0.03). CONCLUSION: Marked differences in sagittal height among different commercially available frequent replacement silicone hydrogel lenses exist. Different lenses with the same package base curve value had marked differences in CL-SAG, with potential clinical significance on-eye in terms of lens behavior. The inter CL-SAG variance in the spherical lens group was smaller than in the toric lens group.