Cationorm

The pharmaceutical ingredient of ataluren was obtained from Sigma-Aldrich (St. Quentin Fallavier, France). DMSO USP grade was provided from Wak-Chemie Medical GmbH (Cryosure, Steinbach, Germany). Pharmaceutical grade castor oil was provided from Cooper (Melun, France). Pharmaceutical hydroxypropylcellulose and tween 80 were provided from Inresa-Pharma (Bartenheim, France). Other chemicals were of analytical grade. Titanium dioxide (99.5% Aeroxide^® P25, nanopowder, average primary particle size 21 nm) came from Sigma Aldrich (St. Quentin Fallavier, France). All solvents used were HPLC grade from Merck (Darmstadt, Germany). Cationorm^® was obtained from Santen (Evry, France) and contained mineral oils, cetalkonium chloride, tyloxapol, poloxamer 188, glycerin, buffer system (Tris-HCl/trometamine), and water for injection. The sterile preservative-free low-density polyethylene (LDPE) multidose opaque eyedropper Novelia^® was obtained from Nemera (La Verpillere, France) and distributed by CAT laboratory (Montereau, France). It was chosen for its capacity to maintain sterility in normal use and under conditions of misuse and extended use, including an anti-return valve system with a silicone membrane.

Participants in both cohorts were randomized to either receive a cationic nanoemulsion (CN, Cationorm^®; Santen Pharmaceutical, Munich, Germany) that contains cetalkonium chloride, liquid paraffin, glycerol, tyloxapol, poloxamer 188, tris hydrochloride and tromethamine) or a completely non-aqueous liquid that only contains perfluorohexyloctane (F6H8), a semifluorinated alkane (SFA, Evotears^® Ursapharm Arzneimittel GmbH, Saarbrücken, Germany).