Polymeric Cyclosporine A Formulation For Dry Eye Syndrome Treatments In Experimental Dry Eye Rabbit.
Published 2023 - 41st Congress of the ESCRS
Reference: PO0762 | DOI: 10.82333/t5df-y503
Authors: Kai-Shin Luo* 1 , Min-Yen Hsu 1
1Ophthalmology,Chung Shan Medical University,Taichung,Taiwan, Province of China
Restasis® has been approved by U.S. Food and Drug Administration (FDA) to treat dry eye syndrome; however,there are some limitations of efficient treatment due to very uncomfortable side effects. In this study, we designed a polymeric formulation of cyclosporine A to reduce the side effects for dry eye syndrome treatments in-vivo.
Topical cyclosporine A lotions (Restasis® 0.05% cyclosporine A) has two major limitations: (1) high uncomfortable side effect rate, such as pain or burning sensation, around 11 to 25%) (2) therapeutic effects required at least 2 to 6 months. We modified current cyclosporine A nano-carrier lotion with cyclosporine A prolonged the remaining of drug on the ocular surface and enhanced the transcorneal ability. We expected reducing discomfort and facilitating the treating duration.
The formulation was prepared by solvent evaporation method. The dry eye syndrome on New Zealand White rabbits were induced by topically applying the four weeks of 0.1% of alkyldimethylbenzylammonium chloride (BAK) solution with thrice-daily. The procedure of animal modelwas similar as reference. Rabbits were randomly divided into four groups. First group was blank, second group applied commercial artificial tear, third group applied our formulation drop, and fourth group applied Restasis. All the treatment was similar as the treatment of Restasis. The fluorescence staining and conjunctival impression cytology (CIC) were measured and collected from rabbits in this study.
The florescence stain showed an obvious green region and CIC showed the decrease of the goblet cell number. Both data indicated the rabbits had severe dry eye after the BAK inducement. After the treatment, the florescence stain showed reduction of green region both formulation group and Restasis group, and green region of treatment group almost disappeared. The CIC showed the recovery of goblet cell both formulation and Restasis group, and the goblet cell number did not have significant difference between formulation and Restasis group.
To approach the reason that may cause dry eye syndrome on patient, we chose the preservative which usually appeared on commercial eye drop to establish the animal model. Although the results showed that the polymeric formulation drop had similar treatment effect as commercial drug, we observed the tolerability of polymeric formulation was better than Restasis when we applied to rabbits. Therefore, this formulation of cyclosporine A maybe overcome the current limitations; On the other hands, the treatment of Restasis was usually accompanied uncomfortable side effect.