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R Michael Dutescu, Claudia Panfil, Olivia M Merkel, Norbert Schrage; Semifluorinated alkanes as a liquid drug carrier system for topical ocular drug delivery. Invest. Ophthalmol. Vis. Sci. 2014;55(13):460.
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Semifluorinated alkanes (e.g. perfluorobutylpentane F4H5, perfluorohexyloctane F6H8) are inert, non-toxic fluids capable of dissolving lipophilic drugs. The aim of this study is to assess the bioavailability and safety of semifluorinated alkanes as drug solvents for topical ocular application of Cyclosporine A (CsA).
A commercially available CsA formulation (Restasis®, 0.05 % CsA in castor oil) was tested against two novel solvents: a) F4H5/ Ethanol (0.5 w/w %) with 0.05 % CsA, and b) F6H8/ Ethanol (0.5 w/w %) with 0.05 % CsA. Formulas were tested on rabbit corneas cultured on an artificial anterior chamber with a constant flow of an aqueous humor supplement (Ex Vivo Eye Irritation Test (EVEIT) system). Anterior chamber fluids were sampled at multiple time points to analyze the CsA concentration by HPLC in a single and repeated application regimen. Photographs of fluorescein sodium stained corneas were recorded for corneal toxicity evaluation. The impact of CsA formulas on the intactness of the corneal barrier function was tested after drug application by fluorescein sodium corneal diffusion experiments. The influence on the corneal metabolism was analyzed by glucose and lactate concentrations.
Restasis® did not pass the corneal barrier after short term application; however, CsA/F4H6 reached a maximum of 152.95 ng/ml, and CsA/F6H8 peaked at a maximum of 15.12 ng/ml in anterior chamber fluid samples. After repeated applications for 8 hours, Restasis® reached 21.07 ng/ml of CsA compared to 247.62 ng/ml and 174.5 ng/ml for F4H5 and F6H8, respectively. No corneal toxicity was observed in any setting.
In contrast to commercially available CsA in castor oil, CsA dissolved in semifluorinated alkanes reached therapeutic inner ocular concentrations after topical administration that could possibly lead to the replacement of systemic applications of CsA for the treatment of inflammatory ocular diseases.
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