Abstract: AimTo prepare diclofenac sodium liposomes and observe its ocular pharmacokinetics in rabbits. MethodsThe diclofenac sodium cationic liposomes were prepared by reverse-phase evaporation methods and the formula of liposome was optimized with uniform design. HPLC method was established and validated for the determination of diclofenac sodium in precornea, cornea and aqueous humor of rabbit eye. Liposome and eyedrop solution 50 μL with total 50 μg diclofenac sodium were instilled to eyes of rabbits, separately. Samples of tear, cornea and aqueous humor were collected at different time intervals after rabbits were sacrificed. The ocular pharmacokinetics was investigated by the concentration-time data of tear, cornea and aqueous humor. ResultsThe mean particle size of the diclofenac sodium liposomes was 226.5 nm with zeta potential of +18.1 mV. The entrapment efficiency reached 63%. Compared with solution, liposome was characterized by slower clearance in precornea. The concentration of diclofenac in cornea and aqueous humor instilled with liposome were higher than that with eye-drop solution. C_max of diclofenac sodium in aqueous humor instilled with liposome and eye-drop solution were (0.69±0.25) and (0.48±0.19) μg·mL^-1 and (36.68±11.7) and (21.82±8.6) μg·g^-1 in cornea, respectively. But no significant difference were found to T_max in aqueous humor and cornea between liposome and eye-drop, T_1/2 of diclofenac in aqueous humor and cornea with liposome were longer than that with eye-drop solution. The ocular bioavailability of liposome in aqueous humor was 211% compared with that of eye-drop. ConclusionDiclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.