Distribution of Cyclosporine A in Ocular Tissues After Topical Administration of Cyclosporine A Cationic Emulsions to Pigmented Rabbits

Abstract

These data demonstrate that the CsA cationic emulsions were more effective than Restasis at delivering CsA to target tissues, thus confirming the potential advantage of cationic emulsions over anionic emulsions as vehicle for ocular drug delivery for the treatment of ocular surface diseases.

Benefits of cetalkonium chloride cationic oil-in-water nanoemulsions for topical ophthalmic drug delivery

“…[46] Interestingly, a second peak of ciclosporin absorption was observed in the cornea with the 0.05% ciclosporin cationic o/w nanoemulsion two hours post instillation (and even 11 h after instillation with the 0.1% ciclosporin cationic o/w nanoemulsion), while no such peak was observed with the anionic o/w nanoemulsion. [17,46] The presence of this second peak is a strong argument in favour of an extended ocular residence time with cationic o/w nanoemulsions. The extended ocular residence time of the cationic o/w nanoemulsion was suggested following the instillation of a latanoprost-loaded cationic o/w nanoemulsion.…”

“…The pharmacokinetic data demonstrated that ciclosporin's area under the curve (AUC) with the cationic o/w nanoemulsion was approximately twice the one observed with the anionic o/w nanoemulsion (AUC: 26477 vs 14210 ng/g.h, for the cationic vs anionic nanoemulsion, respectively). The maximum ciclosporin concentration ( C max ) in the cornea for the cationic o/w nanoemulsion following instillation was 1371.8 ng/g, while it was only 747.8 ng/g for the anionic o/w nanoemulsion . Interestingly, a second peak of ciclosporin absorption was observed in the cornea with the 0.05% ciclosporin cationic o/w nanoemulsion two hours post instillation (and even 11 h after instillation with the 0.1% ciclosporin cationic o/w nanoemulsion), while no such peak was observed with the anionic o/w nanoemulsion .…”

“…The maximum ciclosporin concentration ( C max ) in the cornea for the cationic o/w nanoemulsion following instillation was 1371.8 ng/g, while it was only 747.8 ng/g for the anionic o/w nanoemulsion . Interestingly, a second peak of ciclosporin absorption was observed in the cornea with the 0.05% ciclosporin cationic o/w nanoemulsion two hours post instillation (and even 11 h after instillation with the 0.1% ciclosporin cationic o/w nanoemulsion), while no such peak was observed with the anionic o/w nanoemulsion . The presence of this second peak is a strong argument in favour of an extended ocular residence time with cationic o/w nanoemulsions.…”

Self-Assembling Colloidal System for the Ocular Administration of Cyclosporine A

“…The average drug concentration in the cornea for the micellar CsA solution was 1557 6 407 ng CsA /g cornea . In comparison with the tissue levels reported by Daull et al 25 and Di Tommaso et al, 21,22 it would be possible to lower the number of applications per day compared with that of Restasis, which should be administered at least twice a day. These values agree well with literature data.…”

Novel Formulations for Antimicrobial Peptides

“…The first and only US FDA approved and commercially available formulation Restasis ® is a 0.05% CsA oil-in-water emulsion that does not deliver CsA to the corneal tissue [126]. Alternative formulations are the polymeric MPEG-hexPLA/CsA micelles [118,119,122], the cationic oil-in-water nanoemulsions leading to approximately 350 ng CsA /g cornea, 3 h after a single instillation [127,128,129] and the nonionic micelles of Solutol HS15 (poly oxyethylene esters of 12-hydroxystearic acid) with low toxicity in vivo [130]. Polymeric micelles [106,122] and cationic emulsions significantly increase CsA tissue levels after single and multiple dosing in vivo [127,128,129].…”