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Saman Mohammadi, Lyndon Jones, Maud Gorbet; Investigation of Latanoprost Release from Contact Lens Materials Using in vitro Cell Models. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5472.
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Drug delivering contact lenses (CL) may enhance both drug delivery efficacy and patient compliance with the drug regimen. Although in vivo studies are required to prove efficacy, in vitro corneal models can prove valuable to compare release profiles and identify the most promising candidates for in vivo studies. This study investigated the uptake and delivery of Latanoprost by commercially available CL using three differing in vitro cell models.
The in vitro models used diffusion through a polyethylene terephthalate (PET) filter only (no cells), a PET filter with a monolayer of human corneal epithelial cells (HCECs) and a PET filter with stratified HCECs, all submerged in keratinocyte serum-free medium. Four CL materials (balafilcon A; galyfilcon A; senofilcon A; omafilcon A), were soaked for 24hrs in one of the two forms of a glaucoma drug, Latanoprost (50 μg/ml) and Latanoprost Free-Acid (50 μg/ml). The lenses were then placed on the various models (n=3) and diffusion of the drug through the models was measured after 1, 3, 6 and 24 hours. To compare release profiles with serum-free medium, a drug release in phosphate buffered saline (PBS) with the “no cell” model was performed over 24hrs.
Over a 24hr period, drug release in PBS was not significantly different from serum-free medium- However, the release in presence of cells was higher (e.g., for galyfilcon A, latanoprost release in presence of cells was significantly different from no cells model, p=0.014). Similar differences were observed for other contact lens types except for the conventional hydrogel omafilcon A. For both drugs, similar release profiles were observed for monolayer and stratified cell culture models. In contrast, the latanoprost free-acid release in the no-cell model was higher (p=0.038) due to higher solubility of the free acid form of the drug in medium. In a monolayer model with paraformaldehyde-treated cells, a release similar to no cells model was observed, further highlighting the importance of metabolically active cells.
Latanoprost is a lipophilic prodrug in which the ester bond in the α-chain can be metabolized by cells into an alcohol and the latanoprost free-acid (active drug) to increase bioavailability. Our results highlight the importance that in vitro experimental models and the presence of cells may have on determining the release profile of a drug delivery material.
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