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Cationic Hyaluronic Acid-Modified Cyclosporin Micelles Used for Ocular Drug Delivery

Author(s): Y. N. Wang, R. Yan, Q. H. Wang, Z. H. Wu, H. Zhang and L. Gan*
Shanghai Institute of Technology, School of Chemical and Environmental Engineering, Shanghai 200120, China

Correspondence Address:
L. Gan, Shanghai Institute of Technology, School of Chemical and Environmental Engineering, Shanghai 200120, China, E-mail:

At present, the drugs used to treat dry eye are mainly ocular topical drugs, with only 5 % of the drugs are absorbed, which on the market have adverse reactions, such as eye pain, eye burns, conjunctival hyperemia and poor patient compliance. In order to reduce irritation and improve bioavailability, a new type of ocular drug delivery system, mixed micelles modified with cationic hyaluronic acid was studied by rotary evaporation method. Vitamin E tocopheryl polyethylene glycol succinate and polyoxyethylene hydrogenated castor oil, two non-ionic surfactants are used for the preparation of cyclosporin micelles. Finally, the micelles were modified with cationic hyaluronic acid to form the final formulation named cationic hyaluronic acid modified cyclosporin A nanomicelle, which was designed with particle size of 17.21 nm, polydispersity index of 0.221, zeta potential of -23.4 mV and osmotic pressure of 299 mOsmol/kg. The release rate of cyclosporin A nanomicelle in vitro reached 88 %, and the preparation showed reduced surface tension (34.46 mN/m) and contact angle (22.8°), which indicated that cyclosporin A nanomicelle had better wetting and spreading properties. Transmission electron microscope showed that the preparation was spherical, homogeneous and no aggregates. After modification with cationic hyaluronic acid, the corneal permeability and apparent permeability increased by about 1.4 times and 1.3 times respectively, indicating that cyclosporin A nanomicelle can improve corneal penetration and improve bioavailability. Draize test of rabbit eye surface showed that cyclosporin A nanomicelle has no ocular irritation. In conclusion, Cationic hyaluronic acid modified cyclosporin A nanomicelle might be a promising ocular drug delivery system for the treatment of dry eye.

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