Bringing comfort to the masses: a novel evaluation of comfort agent solution properties.

Ocular comfort agents are molecules that relieve ocular discomfort by augmenting characteristics of the tear film to stabilize and retain tear volume and lubricate the ocular surface. While a number of clinical comparisons between ocular comfort agent solutions are available, very little work has been done correlating the properties of specific comfort agents (species, molecular weight, and water retention) and solution properties (concentration, viscosity, zero shear viscosity, and surface tension) to the performance and effectiveness of comfort agent solutions. In this work, comfort-promoting properties related strongly to comfort agent concentration and molecular weight, the first objective demonstration of this relationship across diverse comfort agent species and molecular weights. The comfort agents with the greatest comfort property contributions (independent of specific molecular weight and concentration considerations) were hyaluronic acid (HA), hydroxypropyl methylcellulose (HPMC), and carboxymethylcellulose (CMC), respectively. The observed, empirical relationships between comfort property contribution and comfort agent species, solution properties, comfort agent molecular weight, and solution concentration was used to develop novel comfort agent index values. The comfort agent index values provided much insight and understanding into the results of experimental studies and/or clinical trials and offer potential resolution to numerous conflicting reports within the literature by accounting for the difference in comfort agent performance due to molecular weight and concentration of comfort agents. The index values provide the first objective, experimental validation and explanation of numerous general trends suggested by clinical data.

Adjusting biomaterial composition to achieve controlled multiple-day release of dexamethasone from an extended-wear silicone hydrogel contact lens.

PURPOSE: To alter the composition and structure of silicone hydrogel contact lenses to achieve controlled release of dexamethasone and evaluate the lens optical and mechanical properties compared to commercial lenses. There is a tremendous need for controlled release of drugs from ocular biomaterials as the majority of ophthalmic drugs are delivered via topical eye drops, which have low bioavailability and patient compliance. METHODS: Poly(PDMS-co-TRIS-co-DMA) contact lenses were synthesized with varying PDMS/TRIS:DMA ratios (0.25:1, 0.67:1, 1.5:1) as well as with additional crosslinking monomers. Lenses were characterized via in vitro release studies in a microfluidic device at ocular flowrates and in large well-mixed volumes, optical quality studies over visible wavelengths, mechanical analysis, and determination of polymer volume fraction in the swollen state. RESULTS: Extended and controlled release of therapeutically relevant concentrations of dexamethasone was achieved for multiple day, continuous wear up to 60 days at in vitro ocular flowrates. Release was delayed due to a combination of increased hydrophobic to hydrophilic composition and the inclusion of additional structural constraints, both of which decreased the polymer volume fraction in the swollen state. However, decreased mass release rates were at the expense of increased modulus and decreased lens flexibility. All lenses had high optical clarity (∼90% transmittance) and contained highly oxygen permeable siloxane composition similar to those found in commercial silicone hydrogel lenses, but they had poor flexibility for use as soft contact lenses. CONCLUSIONS: Based on our results, the lenses described herein likely have too high of a modulus for use as extended-wear, soft contact lenses with drug release. Therefore, other controlled release methods would be better suited for maintaining adequate mechanical properties and achieving controlled and extended release for the duration of wear in soft, silicone hydrogel contact lens biomaterials. However, these biomaterials may find clinical use as more rigid gas permeable contact lenses or inserts.

Extended release of high molecular weight hydroxypropyl methylcellulose from molecularly imprinted, extended wear silicone hydrogel contact lenses.

Symptoms of contact lenses induced dry eye (CLIDE) are typically treated through application of macromolecular re-wetting agents via eye drops. Therapeutic soft contact lenses can be formulated to alleviate CLIDE symptoms by slowly releasing comfort agent from the lens. In this paper, we present an extended wear silicone hydrogel contact lens with extended, controllable release of 120 kDa hydroxypropyl methylcellulose (HPMC) using a molecular imprinting strategy. A commercial silicone hydrogel lens was tailored to release approximately 1000 µg of HPMC over a period of up to 60 days in a constant manner at a rate of 16 µg/day under physiological flowrates, releasing over the entire range of continuous wear. Release rates could be significantly varied by the imprinting effect and functional monomer to template ratio (M/T) with M/T values 0, 0.2, 2.8, 3.4 corresponding to HPMC release durations of 10, 13, 23, and 53 days, respectively. Lenses had high optical quality and adequate mechanical properties for contact lens use. This work highlights the potential of imprinting in the design and engineering of silicone hydrogel lenses to release macromolecules for the duration of wear, which may lead to decreased CLIDE symptoms and more comfortable contact lenses.

Molecularly imprinted therapeutic contact lenses.

IMPORTANCE OF THE FIELD: There exists a considerable unmet need for more efficacious delivery of ocular therapeutics. Contact lenses have been developed with high loading and controllable sustained release to overcome limited patient compliance and significant ocular transport limitations. This can best be achieved by extending and controlling the residence time of drugs on the eye surface and thereby limiting drug loss by lacrimation, drainage and non-productive absorption. AREAS COVERED IN THE REVIEW: Within hydrogels, molecular imprinting can be used to create memory for template molecules embedded within a flexible macromolecular network. Control in therapeutic loading and delay of release have been demonstrated with careful attention to the functional monomer/template ratio, the diversity of functional monomers, and the polymer backbone and network structure. Experimental work has also confirmed that macromolecular memory and not structural differences or phenomena are responsible for delayed drug release kinetics compared with non-imprinted systems. A therapeutically relevant amount of drug can be loaded for release to occur over multiple days, which allows the technique to be applied to daily-wear and extended-wear contact lenses. WHAT THE READER WILL GAIN: The focus of this article is to review the emerging field of molecularly imprinted contact lenses and highlight significant accomplishments, trends, as well as future strategies and directions. TAKE HOME MESSAGE: In the past 8 years, molecular imprinting has been used to produce therapeutic contact lenses with enhanced loading and delayed release. Progress in the field has mostly included low-molecular-weight therapeutics such as anti-glaucoma, antihistamine, antibiotic and anti-inflammatory therapeutics used to treat anterior eye disorders. Recently, high molecular weight comfort molecules have also been successfully demonstrated. Current methods can produce lenses of suitable thickness, water content, and mechanical and optical properties compared with commercial lenses on the market today.