Sustained Delivery of Olopatadine from Vitamin-E Loaded Contact Lenses.

Purpose: Topical antihistamines, such as olopatadine hydrochloride, an H1 receptor antagonist, are commonly prescribed for treating allergic conjunctivitis. Drug delivery via eye drops has many deficiencies including a short residence time due to tear drainage via the nasolacrimal duct, which results in a low bioavailability and potential for side effects. These deficiencies could be mitigated by a drug-eluting contact lens such as the recently approved ACUVUE® THERAVISION™ WITH KETOTIFEN which is a daily disposable etafilcon, a drug-eluting contact lens with ketotifen (19 µg per lens). Here, we investigate the feasibility of designing a drug-eluting lens with sustained release of olopatadine for treating allergies using an extended wear lens. Methods: Nanobarrier depots composed of vitamin-E (VE) are formed through direct entrapment by ethanol-driven swelling. The drug-loaded lenses are characterized for transparency and water content. In vitro release is measured under sink conditions and fitted to a diffusion control release model to determine diffusivity and partition coefficient. Results: In vitro studies indicate that ACUVUE OASYS® and ACUVUE TruEye™ lenses loaded with ∼0.3 g of VE/g of hydrogel effectively prolong olopatadine dynamics by 7-fold and 375-fold, respectively. Incorporation of VE into the lenses retains visible light transmission and other properties. Conclusion: The VE incorporation in commercial lenses significantly increases the release duration offering the possibility of antiallergy extended wear lenses.

Commercialization challenges for drug eluting contact lenses.

INTRODUCTION: Eye drops are commonly used for delivering ophthalmic drugs despite many deficiencies including low bioavailability and poor compliance. Contact lenses can deliver drugs with high bioavailability but commercial contacts release drug rapidly, limiting benefits and necessitating modifications to improve the drug release characteristics. AREAS COVERED: This review covers the common approaches to prolong the release rates of drugs from contact lenses including molecular imprinting, incorporation of nano/microparticles, vitamin-E barriers, and layered/implant contact lenses. It also evaluates their suitability for commercialization and discusses challenges that need to be addressed before commercialization is possible. EXPERT OPINION: In spite of many benefits of contact lenses compared to eye drops, a drug-eluting contact lens has not emerged in the market due to many reasons including potential safety risks, patient and practitioner acceptance, and production and storage factors. Importantly, changes in the critical lens properties must also be considered such as ion and oxygen permeability, loss in modulus, optical and swelling properties, and protein adherence upon drug loading. Many technologies have addressed scientific and commercialization challenges and are currently being tested both in animal and clinical studies. It is likely that a drug-eluting contact lens will be commercialized in the future.

Effect of vitamin-E integration on delivery of prostaglandin analogs from therapeutic lenses.

HYPOTHESIS: Glaucoma is effectively treated by prostaglandin analogs. Low corneal bioavailability (<5%) of daily-instilled prostaglandin drops complemented by frequent application results in low patient compliance (<50%). One alternative route is ocular delivery via commercial hydrogel contact lens. Commercial lenses, however, release prostaglandins rapidly in a few hours owing to their small molecular size, resulting in toxic side-effects. Here, the feasibility of sustained prostaglandin, namely bimatoprost and latanoprost delivery by vitamin-E integrated polymeric hydrogels is explored. Inclusion of these barriers is expected to augment transport resistance and influence delivery rates. EXPERIMENTS: Lens immersion in vitamin-E concentrated ethanol is done to enable formation of nano-barrier depots. FINDINGS: Pilot in vitro studies indicate that ACUVUE® OASYS® and ACUVUE® TruEye™ lenses loaded with ∼0.2 g of vitamin-E/g of hydrogel effectively prolong bimatoprost dynamics by 10-40-fold, delivering therapeutic dosages for >10 days. Incorporation of vitamin-E into the lenses retains visible light transmission and other properties. Further, vitamin-E integration does not influence latanoprost transport. An in vivo model involving coupled mass transport in the lens and post-lens tear film (POLTF) domains predicts >50% corneal bioavailability of bimatoprost delivered via modified lenses.

Pigmented contact lenses for managing ocular disorders.

Blocking a selected wavelength range from the light spectrum can have multiple benefits. Ultra-violet (UV) radiation is detrimental to the retina, necessitating its blocking through sunglasses and contact lenses. The near-visible light also has enough energy to cause damage but, is typically not blocked by commercial lenses. Filtering light can also be useful to patients with migraines, amblyopia, and color blindness. Here, to achieve blocking, incorporation of pigments extracted from colored agro-products into contact lenses is explored. Pigment extraction from food powders including turmeric, spinach, paprika, and woad powders in ethanol is demonstrated. Lens immersion in pigment concentrated ethanol is done to facilitate swelling, allowing rapid pigment uptake. Pigment incorporation ensures the absence of visible light scattering, lens opacity, and leaching. The characterization of pigmented lenses is done through absorptivity and transmittance measurements. Degradation measurements investigate the stability of the green pigment extract from spinach powder with time. p-HEMA and silicone hydrogels loaded with >400 µg/g turmeric pigment act as class 1 UV blockers retaining >90% visible light transparency and screening >95% of the UVR spectra. Spinach, paprika, and woad powder loaded silicone lenses mitigate >20% visible light transmission from selective wavelengths finding applications in photophobia, amblyopia treatment, and color vision deficiency management.

Incorporation of drug particles for extended release of Cyclosporine A from poly-hydroxyethyl methacrylate hydrogels.

Cyclosporine A is prescribed for a number of ophthalmic applications such as dry eyes, uveitis in children and adolescents, vernal keratoconjunctivitis, and peripheral ulcerative keratitis. Extended release of cyclosporine from contact lenses has been explored due to the significant benefits of increased bioavailability in comparison with eye drops. Incorporation of drug loaded particles is considered to be a promising approach for increasing the drug release duration. Here we explore the feasibility of extended release of cyclosporine and possibly other hydrophobic drugs by dispersing particles that are 100% drug rather than drug loaded particles. The expected benefits are high drug loading and extended release. Specifically, we explore transport of cyclosporine in hydroxyethyl methacrylate gels for the case when the gel is loaded with high concentration of drug leading to in situ formation of particles. We explore whether we can increase the release duration from the gels by incorporation of the particles, without sacrificing light transmission which is a critical property for contact lenses. Hydrogels were prepared by free radical UV initiated polymerization with drug dissolved in the monomer solution at varying loadings. Drug release kinetics were measured from the particle loaded lenses and fitted to the Higuchi model to determine the diffusivity. The measured diffusivity is two orders of magnitude lower than estimates from Brinkman model. The differences were attributed to the high partition coefficient of about 150, which implies that a majority of the drug in the gel is bound to the polymer. The bound drug can diffuse along the surface or desorb and diffuse. The diffusivity estimates match the measured values after binding is taken into consideration. Light transmittance was measured to determine whether particle incorporation reduces the transparency. Results showed that the drug release duration could be controlled by increasing the drug loading but the transmittance was significantly reduce particularly at high drug loadings, which suggest that this approach may have limited applicability for contact lenses, but could be useful in other applications where light transmission is not critical.

Relationship between single-file diffusion of mixed and pure gases in dipeptide nanochannels by high field diffusion NMR.

High field NMR diffusometry reveals single-file diffusion of CO/CH4 mixture in dipeptide nanochannels with a coincident mobility for CO and CH4. In contrast to the relationship commonly observed for normal diffusion, this mixture mobility is only slightly smaller than that of pure CO which diffuses much faster than pure CH4.