文献类型：期刊文献

英文题名：Preparation, characterization and pharmacokinetic studies of tacrolimus-dimethyl-β-cyclodextrin inclusion complex-loaded albumin nanoparticles

作者：Gao, Shanshan[1];Sun, Jun[1];Fu, Dongjun[1];Zhao, Hongli[2];Lan, Minbo[2];Gao, Feng[1,2,3]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2012

卷号：427

期号：2

起止页码：410

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000302364500035)】；

基金：The authors acknowledge the financial support from Shanghai nanotechnology leading academic discipline foundation (No. 0852nm05900) and 111 program of China (No. B07023). This work was supported by Science and Technology Commission of Shanghai Municipality (STCSM, contract Nos. 10dz2220500 and 11dz2260600).

语种：英文

外文关键词：FK506/DM-beta-CD inclusion complex; BSA nanoparticle; Sustained-release

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)-beta-cyclodextrin (DM-beta-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-beta-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 -24.9 to -38.4 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-beta-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-beta-CD inclusion complex-loaded BSA nanoparticles display significantly improved delivery efficiency for poorly soluble FK506 or its derivatives. (c) 2012 Elsevier B.V. All rights reserved.