Ocular delivery of cyclosporin A II. Effect of submicron emulsion's surface charge on ocular distribution of topical cyclosporin A

The aim of the present work is to compare and to gain useful mechanical understanding of the effect of surface charges of the emulsion droplets on topical cyclosporin A penetration through the various ocular tissues. Following one single 50 μl dose into the rabbit eye, it was found that the submicron emulsion vehicle bearing a positive charge enhanced cyclosporin A bioavailability in the conjunctiva and cornea compared to the negatively-charged emulsion. This is probably due to the interaction between the positive charge of the emulsion vehicle surface and the negative charge of the corneal surface at physiological pH. Such an electrostatic interaction was already demonstrated by published ex vivo and in vivo studies and is supported by the present data. The enhanced penetration of CsA in the ocular tissue is apparently mediated by an endocytic mechanism, the occurrence of which can be confirmed by the intermediate results of unpublished cell-culture studies. Nevertheless, the cyclosporin A concentration in the intraocular tissues was low indicating poor drug penetration. In addition, there was no marked drug concentration in the various untreated eye tissues, indicating the lesser contralateral effects exerted by the emulsion dosage forms, irrespective of the droplet surface charge.