Study On Cationized Hyaluronic Acid Modified Cyclosporin A Micelles

Dry eye refers to a type of disease in which the tear film is unstable and the ocular surface is damaged due to the abnormal amount or quality of tear fluid,which leads to ocular discomfort.The cause of dry eye is complicated.The current treatment method is mainly ocular topical medication.However,due to the corneal barrier and nasolacrimal duct drainage,the drug stays in the eye for a short time and the bioavailability is low.In addition,the commercially available preparations have adverse reactions such as eye pain,tearing and eye congestion.Therefore,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.In this paper,cyclosporine A was used as a model drug to design and investigate the effect of cationic hyaluronic acid modified micelles in vivo and in vitro,which provided ideas for the design of new dosage forms of ocular drug delivery in future.The cationic hyaluronic acid modified cyclosporin A nano micelles(0.07%CHA1-CsANM)was designed with particle size of 17.21 nm,polydispersity index(PDI)of 0.221,Zeta-potential of-23.4 mV and osmotic pressure of 299 mosmol/kg.The release rate of CHA-CsANM in vitro reached 88%,and the preparation showed reduced surface tension(34.46 mN/m)and contact angle(22.8°),which indicated that 0.07%CHA1-CsANM had good wetting and spreading properties.Transmission electron microscopy 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 0.07%CHA1-CsANM can improve corneal penetration and improve bioavailability.The Draize test showed that 0.07%CHA1-CsANM has no irritation to the eyes.Cationic hyaluronic acid modified nano micelles are expected to be an ideal ophthalmic drug delivery system for the treatment of dry eye.