摘要
目的研究双氯酚酸钠脂质体的制备方法并考察其在家兔眼部的药代动力学特征。方法采用逆相蒸发法制备双氯酚酸钠正电荷脂质体。脂质体和滴眼液滴眼后家兔采用高效液相色谱法测定角膜前、角膜和房水中药物浓度。结果制得的脂质体平均粒径为226.5 nm,多分散度为0.214,ζ电位为+18.1 mV,经均匀设计优化处方,包封率可达到63%。0.1%双氯酚酸钠脂质体和滴眼液两种制剂家兔局部滴眼后的药代动力学研究显示,脂质体可延缓药物在角膜前的清除,增加角膜中药物的浓度,药物在房水中半衰期延长,以滴眼液为参比制剂,相对生物利用度为211%。结论双氯酚酸钠正电荷脂质体可以增加药物在角膜前的滞留时间,提高角膜渗透性及药物在眼部的生物利用度,减少滴眼次数。
Aim 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 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. Results The mean panicle 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. Cmax 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 in aqueous humor and cornea between liposome and eye-drop, T1/2 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. Conclusion Diclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.
出处
《药学学报》
CAS
CSCD
北大核心
2006年第11期1094-1098,共5页
Acta Pharmaceutica Sinica
作者简介
通讯作者Tel：86—535—6706021，Fax：86—535—6706036，E-mail：sunkx@ytu．edu．cn
