Hydrogel-based Contact Lens Research Articles

Formulation development and evaluation of therapeutic contact lens loaded with ganciclovir.

In the present investigation ganciclovir (GAN) loaded microparticles dispersed in hydrogel-based contact lenses were fabricated, characterized and evaluated for eye irritation. GAN-Hydroxy Propyl Methyl Cellulose (HPMC) microparticles were prepared by solvent evaporation method and evaluated for entrapment efficiency, drug content and drug release. The Polyhydroxyethylmethacrylate (pHEMA) contact lenses were synthesized by free radical polymerization reaction using crosslinkers like ethylene glycoldimethacrylate and photoinitiator such as IRGACURE 1173®, in UVB light, λ 365nm. The GAN-HPMC microparticles when incorporated into the premonomer mixture and polymerized together give rise to a particle dispersion system in the hydrogel contact lenses. The contact lenses were studied for surface morphology, transmittance, swelling, drug release, Na+ion permeability and hens egg test chorioallantoic membrane assay (HETCAM). Hydrogel contact lens exhibited satisfactory surface morphology, transmittance, swelling, Na+ion permeability (3.72 × 106 mm2/min) and a release of 48h suggesting a potential for prolonged ocular drug delivery. Furthermore, HETCAM exhibited no signs of ocular irritation. The developed delivery platform is a promising alternative to conventional dosage forms like eye drops, suspensions and ointments due to its increase in the residence time attributed to its prolonged release profile.

Recent Applications of Contact Lenses for Bacterial Corneal Keratitis Therapeutics: A Review.

Corneal keratitis is a common but severe infectious disease; without immediate and efficient treatment, it can lead to vision loss within a few days. With the development of antibiotic resistance, novel approaches have been developed to combat corneal keratitis. Contact lenses were initially developed to correct vision. Although silicon hydrogel-based contact lenses protect the cornea from hypoxic stress from overnight wear, wearing contact lenses was reported as an essential cause of corneal keratitis. With the development of technology, contact lenses are integrated with advanced functions, and functionalized contact lenses are used for killing bacteria and preventing infectious corneal keratitis. In this review, we aim to examine the current applications of contact lenses for anti-corneal keratitis.

Phenylboronic acid modified hydrogel materials and their potential for use in contact lens based drug delivery

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding.

SERS optical accumulators as unified nanoplatforms for tear sampling and sensing in soft contact lenses.

Tear analysis has become an invaluable asset in clinical research in order to identify and quantify novel biomarkers for a wide array of conditions. The present work is intended to take this area of study one step further by implementing an innovative sensing platform through which exploration of low-molecular-weight compounds is conducted outperforming traditional analytical technologies. With this aim, carefully engineered plasmonic nanoassemblies have been synergistically combined with molecular-sieving materials giving rise to size-selective samplers with SERS detection capabilities. These architectures have been then integrated onto hydrogel-based contact lenses and tested in simulated tear fluids in order to evidence their operational features. Through this approach, a prolonged analyte accumulation can be realized, thus providing a competitive advantage in those scenarios where concentration of biomarkers is typically low or minimum sample volumes are not met. Additionally, quenching of metabolic flux and analyte extraction protocols can be circumvented, hence preventing the intrinsic physical and chemical interferences stemming from these procedures. The obtained results render these sensing platforms as promising medical devices, and constitute a great opportunity in order to expand the clinical toolkit in tear analysis.

Steroid-eluting contact lenses for corneal and intraocular inflammation

Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. Statement of SignificanceInflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses.

Femtosecond micro-machining of hydrogels: parametric study and photochemical model including material saturation

We report on the effects of various laser system parameters on the magnitude of phase change induced inside hydrogel-based contact lens materials in the two-photon absorption limit via a laser induced refractive index (LIRIC) technique. In comparison with near infrared writing at 1035 nm where four-photon absorption process dominates, blue writing at 405 nm allows for the achievement of a decent amount of phase change (one wave) with a low power and a fast scan speed due to a more efficient two photon absorption process. Efficacy of the LIRIC process could be further improved by taking advantage of intermediate repetition rate laser pulses instead of high repetition rate (> 60 MHz) pulses or low repetition rate (< 500 KHz) pulses. A generally applicable photochemical model based on multiphoton absorption mechanism and pulse overlapping effect in two dimensions is proposed to predict the scaling behavior of the induced phase change. A modified photochemical model incorporating a saturation factor is developed to account for the behavior at large phase shifts. The modified photochemical model also helps explain the inapparent dependence of the phase change on numerical aperture (NA) at low irradiation doses and the observed sub-linear inverse dependence on scan speed.

Quantitative photochemical scaling model for femtosecond laser micromachining of ophthalmic hydrogel polymers: effect of repetition rate and laser power in the four photon absorption limit

We report on the effect of laser repetition rate on the refractive index (RI) change or phase change induced by the femtosecond micromachining hydrogel-based ophthalmic materials. A repetition rate tunable femtosecond ytterbium (Yb) doped fiber laser was used to study the relation between the laser-induced phase change and the pulse repetition rate in the range of 1 MHz to 60 MHz. We present both the qualitative and quantitative results of the laser-induced phase change obtained in hydrogel-based contact lenses at different repetition rates and discuss the effect of repetition rate on the magnitude of the phase shift, the optical damage threshold and the maximum achievable phase change just below the optically-induced damage threshold. A photochemical model derived in the four photon absorption limit with pulse overlapping is employed to fit the experimental data obtained at four different repetition rates, 5 MHz, 10 MHz, 15 MHz and 60 MHz. This work contributes to the current knowledge of the response of hydrogel polymers to various laser irradiation parameters and the optimization of laser repetition rates enables femtosecond micromachining of ophthalmic materials at a lower average power and a faster writing speed.

Microfluidic Contact Lenses.

Contact lens is a ubiquitous technology used for vision correction and cosmetics. Sensing in contact lenses has emerged as a potential platform for minimally invasive point‐of‐care diagnostics. Here, a microlithography method is developed to fabricate microconcavities and microchannels in a hydrogel‐based contact lens via a combination of laser patterning and embedded templating. Optical microlithography parameters influencing the formation of microconcavities including ablation power (4.3 W) and beam speed (50 mm s−1) are optimized to control the microconcavity depth (100 µm) and diameter (1.5 mm). The fiber templating method allows the production of microchannels having a diameter range of 100–150 µm. Leak‐proof microchannel and microconcavity connections in contact lenses are validated through flow testing of artificial tear containing fluorescent microbeads (Ø = 1–2 µm). The microconcavities of contact lenses are functionalized with multiplexed fluorophores (2 µL) to demonstrate optical excitation and emission capability within the visible spectrum. The fabricated microfluidic contact lenses may have applications in ophthalmic monitoring of metabolic disorders at point‐of‐care settings and controlled drug release for therapeutics.

An Experimental Model to Study the Impact of Lipid Oxidation on Contact Lens Deposition In Vitro

ABSTRACTPurpose: This study was to establish a controlled in vitro test system to study the effect of lipid oxidation on lipid deposition on contact lenses.Methods: Fatty acids with varying degree of unsaturation were oxidized using the Fenton reaction. The degree of lipid oxidation and the lipid moieties formed during the oxidation were identified and estimated by various lipid staining techniques following separation with thin-layer chromatography, and by measuring thiobarbituric acid reactive substances or peroxides in solution. Two different silicone hydrogel-based contact lenses (Balafilcon A and Senofilcon A) were incubated with fatty acids laced with radioactive tracer oxidized to varying degrees, and the amount of lipid deposition was measured using unoxidized lipid samples as controls.Results: The Fenton reaction together with the analytical methods to analyze the lipid oxidation can be used to control oxidation of lipids to a desired amount. In general, saturated fatty acids are not oxidized, the monounsaturated oleic acid produced peroxides while poly-unsaturated lipids initially produced peroxides and then fragmented into reactive aldehydes. Incubation with mildly oxidized lipids (most likely lipid peroxides) resulted in increased lipid deposition on Balafilcon A lenses compared to unoxidized lipids, but this was not observed for Senofilcon A lenses. Further oxidation of the lipids (carbon chain breakup) on the other hand resulted in diminished lipid deposition for both contact lens types.Conclusions: This study provides a method for inducing and controlling lipid oxidation so that the effect of lipid oxidation on contact lens binding can be compared. It could be shown that the degree of lipid oxidation has different effects on the lipid deposition on different contact lens types.

A Hydrogel-Based Hybrid Theranostic Contact Lens for Fungal Keratitis.

Fungal keratitis, a severe ocular disease, is one of the leading causes of ocular morbidity and blindness, yet it is often neglected, especially in developing countries. Therapeutic efficacy of traditional treatment such as eye drops is very limited due to poor bioavailability, whereas intraocular injection might cause serious side effects. Herein, we designed and fabricated a hybrid hydrogel-based contact lens which comprises quaternized chitosan (HTCC), silver nanoparticles, and graphene oxide (GO) with a combination of antibacterial and antifungal functions. The hydrogel is cross-linked through electrostatic interactions between GO and HTCC, resulting in strong mechanical properties. Voriconazole (Vor), an antifungal drug, can be loaded onto GO which retains the drug and promotes its sustained release from the hydrogel-based contact lenses. The contact lenses also exhibited good antimicrobial functions in view of glycidyltrimethylammonium chloride and silver nanoparticles. The results from in vitro and in vivo experiments demonstrate that contact lenses loaded with Vor have excellent efficacy in antifungal activity in vitro and could significantly enhance the therapeutic effects on a fungus-infected mouse model. The results indicate that this hydrogel contact lenses-based drug delivery system might be a promising therapeutic approach for a rapid and effective treatment of fungal keratitis.

Femtosecond laser writing of freeform gradient index microlenses in hydrogel-based contact lenses

Femtosecond lasers can be used to write a variety of gradient index refractive devices. Writing devices with an arbitrary optical profile (i.e., freeform) requires knowing the functional dependence of the phase change that the wavefront will experience when passing through a region written under different exposure parameters. We measured this dependence as a function of writing speed and power in hydrogel-based contact lenses. Regions of constant refractive index change were written under different conditions and then the phase change was measured with a Mach-Zehnder interferometer and a phase retrieval algorithm. This functional dependence was tested by writing arbitrary Zernike polynomials with varying magnitudes.

MICROMECHANICAL CHARACTERIZATION OF HYDROGEL-BASED CONTACT LENS

A new micro-shaft-poking (MSP) apparatus has been applied for characterizing the mechanical properties of hydrogel-based contact lens. The instrument allows measurement of the force-displacement curve of the contact lens under a wide range of strain and strain rate. The materials display hysteresis and stress relaxation (50-60%) manifested in the experimental compliance curves. In parallel, a Finite Element Analysis (FEA) modeling incorporated with nonlinear elasticity has been performed for simulating the contact lens under large deformation. Through comparison between the simulated results and experimental data, the mechanical properties, e.g., stiffness, of the lens can be quantitatively determined. The viscoelastic characteristic of the lens has also been parametric fitted based on a five-parameter quasi-viscoelastic model.