School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, China.
Int J Nanomedicine. 2010 Feb 2;5:13-23.
Efforts to improve the oral bioavailability of cyclosporine A (CyA) remains a challenge in the field of drug delivery. In this study, glyceryl monooleate (GMO)/poloxamer 407 cubic nanoparticles were evaluated as potential vehicles to improve the oral bioavailability of CyA. Cubic nanoparticles were prepared via the fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by sonication and homogenization. The cubic inner structure formed was verified using Cryo-TEM. The mean diameters of the nanoparticles were about 180 nm, and the entrapment efficiency of these particles for CyA was over 85%. The in vitro release of CyA from these nanoparticles was less than 5% at 12 h. The results of a pharmacokinetic study in beagle dogs showed improved absorption of CyA from cubic nanoparticles as compared to microemulsion-based Neoral((R)); higher C(max) (1371.18 +/- 37.34 vs 969.68 +/- 176.3 ng mL(-1)), higher AUC(0-t) (7757.21 +/- 1093.64 vs 4739.52 +/- 806.30 ng h mL(-1)) and AUC(0-infinity) (9004.77 +/- 1090.38 vs 5462.31 +/- 930.76 ng h mL(-1)). The relative oral bioavailability of CyA cubic nanoparticles calculated on the basis of AUC(0-infinity) was about 178% as compared to Neoral((R)). The enhanced bioavailability of CyA is likely due to facilitated absorption by cubic nanoparticles rather than improved release.
环孢素 A（CyA）的口服生物利用度仍然是药物传递领域的一个挑战。在这项研究中，甘油脂单油酸酯（GMO）/泊洛沙姆 407 立方纳米粒被评估为提高 CyA 口服生物利用度的潜在载体。立方纳米粒通过超声和匀浆使大块 GMO/泊洛沙姆 407 立方相凝胶碎裂来制备。使用 Cryo-TEM 验证了形成的立方内结构。纳米粒的平均直径约为 180nm，这些粒子对 CyA 的包封效率超过 85%。这些纳米粒在 12 小时内的体外释放量不到 5%。在比格犬的药代动力学研究结果表明，与基于微乳的 Neoral((R))相比，CyA 从立方纳米粒中的吸收得到改善；更高的 C(max)（1371.18 +/- 37.34 比 969.68 +/- 176.3ng/mL(-1)），更高的 AUC(0-t)（7757.21 +/- 1093.64 比 4739.52 +/- 806.30ng h/mL(-1))和 AUC(0-无穷大)（9004.77 +/- 1090.38 比 5462.31 +/- 930.76ng h/mL(-1)）。基于 AUC(0-无穷大)计算的 CyA 立方纳米粒的相对口服生物利用度约为 Neoral((R))的 178%。CyA 生物利用度的提高可能是由于立方纳米粒促进了吸收，而不是改善了释放。
