Extended Latanoprost Release from Commercial Contact Lenses: In Vitro Studies Using Corneal Models

Abstract

In this study, we compared, for the first time, the release of a 432 kDa prostaglandin analogue drug, Latanoprost, from commercially available contact lenses using in vitro models with corneal epithelial cells. Conventional polyHEMA-based and silicone hydrogel soft contact lenses were soaked in drug solution ( solution in phosphate buffered saline). The drug release from the contact lens material and its diffusion through three in vitro models was studied. The three in vitro models consisted of a polyethylene terephthalate (PET) membrane without corneal epithelial cells, a PET membrane with a monolayer of human corneal epithelial cells (HCEC), and a PET membrane with stratified HCEC. In the cell-based in vitro corneal epithelium models, a zero order release was obtained with the silicone hydrogel materials (linear for the duration of the experiment) whereby, after 48 hours, between 4 to 6 of latanoprost (an amount well within the range of the prescribed daily dose for glaucoma patients) was released. In the absence of cells, a significantly lower amount of drug, between 0.3 to 0.5 , was released, (). The difference observed in release from the hydrogel lens materials in the presence and absence of cells emphasizes the importance of using an in vitro corneal model that is more representative of the physiological conditions in the eye to more adequately characterize ophthalmic drug delivery materials. Our results demonstrate how in vitro models with corneal epithelial cells may allow better prediction of in vivo release. It also highlights the potential of drug-soaked silicone hydrogel contact lens materials for drug delivery purposes.

Ocular Drug Delivery Role of Contact Lenses

“…6 Initially, a cationic or anionic material in the SCL forms an ionic complex with the drug content in the drug solution. Then, after applying the SCL to the eye, ionic components in the tear fluid, such as sodium, chlorine, or other elements, are gradually replaced with the drug contents.Finally, the drug release is sustained continuously from the SCL.…”

“…Several commercial ocular delivery devices are currently available, including surface located inserts, degradable or non-degradable implants, and in situ forming gels. 6 Contact lenses (CLs) have provided a novel route for ocular drug delivery.…”

“…41 Modifying the drug release through the use of molecular imprinting has also been described in other studies. 42,43 The extended release of Latanoprost 6 and Norfloxacin 44 from imprinted contact lenses has been shown. Silicone hydrogels for the delivery of the antibiotic ciprofloxacin were developed using a molecular imprinting strategy.…”

Recent Advances in Topical Therapeutics for Vitreoretinal Diseases

“…21 To get around this, the contact time and thereby absorption of topical ocular medication can be prolonged by formulations such as gels, ointments, inserts, and contact lenses. 22 The corneal epithelium is a further barrier to drug penetration into the eye, and is considered to be the rate-limiting factor for most drugs, particularly for hydrophilic compounds. It has been estimated that typically less than 5 % of topically applied drug permeates the cornea and reaches intraocular tissues.…”

“…It has been estimated that typically less than 5 % of topically applied drug permeates the cornea and reaches intraocular tissues. [22][23][24] A large portion of drug applied by eye drops is absorbed systemically, either via the conjunctival and eyelid blood vessels, or via the nasopharyngeal mucosa.…”