Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model

Autoři: Seung Pil Bang aff001;  Chang Yeor Yeon aff003;  Nirpesh Adhikari aff003;  Sanjiv Neupane aff003;  Harim Kim aff001;  Dong Cheol Lee aff001;  Myeong Jin Son aff001;  Hyun Gyo Lee aff001;  Jae-Young Kim aff003;  Jong Hwa Jun aff001
Působiště autorů: Department of Ophthalmology, Keimyung University School of Medicine, Dongsan Medical Centre, Daegu, Republic of Korea aff001;  Department of Biomedical Engineering, University of Rochester, Rochester, New York, United States of America aff002;  Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, Republic of Korea aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224805



We aimed to compare the physicochemical properties and in vivo efficacy of commercially available nanoemulsion cyclosporine A (CsA) eyedrops in benzalkonium chloride (BAC)-induced dry eye disease (DED).


Particle size analysis was performed on conventional 0.05% CsA (Restasis, C-CsA) and two new types of 0.05% CsA eyedrops based on a self-nanoemulsifying drug delivery system (SNEDDS, SNEDDS-N and -T). Turbidometry, pH measurements and instability indices of each CsA solution were measured. DED was induced with BAC, and animals were treated with vehicle or CsA preparations. Tear volume and fluorescein staining scores were evaluated on days 7 and 14. Eyes were enucleated and subjected to IHC, TUNEL staining, periodic acid-Schiff (PAS) staining, real-time PCR and western blotting.


Both SNEDDSs had lower and more uniform particle size distribution than C-CsA, and a similar optical density to phosphate-buffered saline and stable pH, in contrast to the high turbidity and unstable pH of C-CsA. Aqueous tear volume and fluorescein staining scores were improved in C-CsA- and SNEDDS-treated mice. Numbers of PAS-positive goblet cells and levels of inflammatory mediators were decreased by both C-CsA and SNEDDS, although SNEDDS resolved inflammation more effectively than C-CsA.


Cyclosporine A eyedrops with SNEDDS have improved physicochemical properties and treatment efficacy in BAC-induced DED.

Klíčová slova:

Apoptosis – Cornea – Cytokines – Emulsions – Eyes – Inflammation – Nanoparticles – Turbidity


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2019 Číslo 11