Ocular pharmacokinetics of dexamethasone cubosomes in rabbit aqueous humor

Aim:To prepare novel cubosome system for effective ocular drug delivery with dexamethasone(DEX) as model drug,and investigate its pharmacokinetic profile in rabbit aqueous humor.Methods:DEX cubosomes was prepared by the method of high-pressure homogenization,and its particle size was determined by the laser particle sizer,and the microstructure observed by cryo-TEM.In addition,Draize method was used to evaluate the ocular irritation of DEX cubosomes.Finally,aqueous humor microdialysis was utilized to evaluate its pharmacokinetics in rabbits.Results:Average diameter of DEX cubosomes was about 200 nm,and the cubic structure of the particles was evident under the cryo-TEM.It was indicated by Draize scores that this dosage form exhibited excellent ocular tolerance.Results of pharmacokinetic profiles in aqueous humor showed that AUC0→240 and cmax of the rabbit group administered with DEX cubosomes were significantly higher than those of the control group(DEX sodium phosphate eye drops),with AUC0→240 of the formulation F1(10% oil content) and F2(20% oil content) is being about 1.8 and 2.9 times higher than those of the control group,respectively(P0.05).Conclusion:The novel ocular drug delivery system of DEX cubosomes was capable of increasing significantly the drug concentration in aqueous humor,and improving the ocular bioavailability.