Supercritical fluid-mediated liposomes containing cyclosporin A for the treatment of dry eye syndrome in a rabbit model: comparative study with the conventional cyclosporin A emulsion

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 3791 - 3800
• Main Authors: Karn, Pankaj Ranjan, Kim, Hyun Do, Kang, Han, Sun, Bo Kyung, Jin, Su-Eon, Hwang, Sung-Joo
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2014; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Alcohol; Animals; Blinking; Carbon dioxide; Complications and side effects; Cornea; cyclosporin A; Cyclosporine; Cyclosporine - analysis; Cyclosporine - chemistry; Cyclosporine - pharmacokinetics; Cyclosporine - therapeutic use; Disease Models, Animal; Dosage and administration; Drug delivery systems; Drug therapy; dry eye syndrome; Dry eye syndromes; Dry Eye Syndromes - drug therapy; Inventors; Lactose; Liposomes; Liposomes - chemistry; Liposomes - therapeutic use; Male; Models, Biological; Molecular weight; Original Research; Particle size; Permeability; Physiological aspects; Rabbits; Scanning electron microscopy; Studies; supercritical fluid; Tears - chemistry; Thin films; South Korea; United States > US; Japan; cyclosporin A; dry eye syndrome; liposomes; supercritical fluid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S65601

The objective of this study was to compare the efficacy of cyclosporin (CsA)-encapsulated liposomes with the commercially available CsA emulsion (Restasis) for the treatment of dry eye syndrome in rabbits. Liposomes containing CsA were prepared by the supercritical fluid (SCF) method consisted of phosphatidylcholine from soybean (SCF-S100) and egg lecithins (SCF-EPCS). An in vitro permeation study was carried out using artificial cellulose membrane in Franz diffusion cells. Dry eye syndrome was induced in male albino rabbits and further subdivided into untreated, Restasis-treated, EPCS, and S100-treated groups. Tear formation in the dry-eye-induced rabbits was evaluated using the Schirmer tear test. All formulations were also evaluated by ocular irritation tests using the Draize eye and winking methods with the determination of CsA concentration in rabbit tears. After the treatment, the Schirmer tear test value significantly improved in EPCS-treated (P=0.005) and S100-treated (P=0.018) groups compared to the Restasis-treated group. The AUC₀₋₂₄ h for rabbit's tear film after the administration of SCF-S100 was 32.75±9.21 μg·h/mg which was significantly higher than that of 24.59±8.69 μg·h/mg reported with Restasis. Liposomal CsA formulations used in this study showed lower irritation in rabbit eyes compared with Restasis. These results demonstrate that the novel SCF-mediated liposomal CsA promises a significant improvement in overcoming the challenges associated with the treatment of dry eyes.