Preparation, characterization and pharmacokinetic studies of tacrolimus-dimethyl-尾-cyclodextrin inclusion complex-loaded albumin nanoparticles

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• 作者：Shanshan Gao^b ; Jun Sun^b ; Dongjun Fu^b ; Hongli Zhao^a ; Minbo Lan^a ; Feng Gao^a ; ^b ; ^c ; ^{fgao@ecust.edu.cn}
• 关键词：FK506/DM-尾-CD inclusion complex ; BSA nanoparticle ; Sustained-release
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：10 May, 2012
• 卷：427
• 期：2
• 页码：410-416
• 文件大小：541 K

摘要

The purpose of the study is to develop a new formulation for clinically used anti-cancer agent tacrolimus (FK506) to minimize the severe side effects. Toward this end, a new formulation method has been developed by complexation of FK506 with an hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-尾-cyclodextrin (DM-尾-CD) using ultrasonic means. The resulting complex displays dramatically enhanced solubility of FK506. Then bovine serum albumin (BSA) nanoparticles were prepared directly from the preformed FK506/DM-尾-CD inclusion complex by the desolvation-chemical crosslinking method, with the size of 148.4-262.9 nm. Stable colloidal dispersions of the nanoparticles were formed with zeta potentials of the range of 鈭?4.9 to 鈭?8.4 mV. The entrapment efficiency of FK506 was increased as high as 1.57-fold. Moreover, notably FK506 was released from the nanoparticles in a sustained manner. As demonstrated, pharmacokinetic studies reveal that, as compared with FK506-loaded BSA nanoparticles, the FK506/DM-尾-CD inclusion complex-loaded BSA nanoparticles have significant increase at T_max, t_1/2, MRT and decrease at C_max. In summary, these results suggest that the drug/DM-尾-CD inclusion complex-loaded BSA nanoparticles display significantly improved delivery efficiency for poorly soluble FK506 or its derivatives.