[Preparation of diclofenac sodium liposomes and its ocular pharmacokinetics].
OBJECTIVE
To prepare diclofenac sodium liposomes and observe its ocular pharmacokinetics in rabbits.


METHODS
The 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 microL with total 50 microg 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.


RESULTS
The 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 diclotenac in cornea and aqueous humor instilled with liposome were higher than that with eye-drop solution. Cmax of diclofenac sodium in aqueous humor instilled with liposome and eye-drop solution were (0.69 +/- 0.25) and (0.48 +/- 0.19) microg x mL(-1) and (36.68 +/- 11.7) and (21.82 +/- 8.6) microg x g(-1) in cornea, respectively. But no significant difference were found to Tmax in aqueous humor and cornea between liposome and eyedrop, T(1/2) of diclofenac in aqueous humor and cornea with liposoine were longer than that with eye-drop solution. The ocular bioavailability of liposome in aqueous humor was 211% compared with that of eyedrop.


CONCLUSIONS
Diclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.
Sun
Kao-xiang
KX
School of Pharmacy, Yantai Unirversity, Yantai 264005, China. sunkx@ytu.edu.cn
Wang
Ai-ping
AP
Huang
Li-jun
LJ
Liang
Rong-cai
RC
Liu
Ke
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004339:Drug Compounding; D008081:Liposomes; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011817:Rabbits; D011897:Random Allocation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008081:Liposomes; D004008:Diclofenac