Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
Int J Pharm. 2010 Aug 30;396(1-2):179-87. doi: 10.1016/j.ijpharm.2010.06.015. Epub 2010 Jun 15.
The object of this study was to design novel self-assembled liquid crystalline nanoparticles (cubosomes) as an ophthalmic delivery system for dexamethasone (DEX) to improve its preocular retention and ocular bioavailability. DEX cubosome particles were produced by fragmenting a cubic crystalline phase of monoolein and water in the presence of stabilizer Poloxamer 407. Small angle X-ray diffraction (SAXR) profiles revealed its internal structure as Pn3m space group, indicating the diamond cubic phase. In vitro, the apparent permeability coefficient of DEX administered in cubosomes exhibited a 4.5-fold (F1) and 3.5-fold (F2) increase compared to that of Dex-Na phosphate eye drops. Preocular retention studies revealed that the retention of cubosomes was significantly longer than that of solution and carbopol gel, with AUC(0-->180min) of Rh B cubosomes being 2-3-fold higher than that of the other two formulations. In vivo pharmacokinetics in aqueous humor was evaluated by microdialysis, which indicated a 1.8-fold (F1) increase in AUC(0-->240min) of DEX administered in cubosomes relative to that of Dex-Na phosphate eye drops, with about an 8-fold increase compared to that of DEX suspension. Corneal cross-sections after incubation with DEX cubosomes demonstrated an unaffected corneal structure and tissue integrity, which indicated the good biocompatibility of DEX cubosomes. In conclusion, self-assembled liquid crystalline nanoparticles might represent a promising vehicle for effective ocular drug delivery.
本研究旨在设计新型自组装液晶纳米颗粒（立方液晶纳米囊）作为地塞米松（DEX）的眼部递药系统，以提高其在眼前部的滞留和眼部生物利用度。DEX 立方液晶纳米囊颗粒是通过在稳定剂泊洛沙姆 407 的存在下，使单油酸甘油酯和水的立方晶相碎裂而产生的。小角 X 射线衍射（SAXR）图谱显示其内部结构为 Pn3m 空间群，表明为金刚石立方相。体外实验中，DEX 立方液晶纳米囊给药的表观渗透系数（F1）和（F2）分别比 Dex-Na 磷酸盐滴眼液增加了 4.5 倍和 3.5 倍。眼前部滞留研究表明，立方液晶纳米囊的滞留时间明显长于溶液和卡波姆凝胶，Rh B 立方液晶纳米囊的 AUC（0-->180min）比其他两种制剂高 2-3 倍。通过微透析评估房水中的体内药代动力学，结果表明，DEX 立方液晶纳米囊给药的 AUC（0-->240min）比 Dex-Na 磷酸盐滴眼液增加了 1.8 倍，与 DEX 混悬剂相比增加了约 8 倍。用 DEX 立方液晶纳米囊孵育后的角膜横截面显示角膜结构和组织完整性不受影响，表明 DEX 立方液晶纳米囊具有良好的生物相容性。总之，自组装液晶纳米颗粒可能是一种有前途的有效眼部药物传递载体。
