Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs
Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs
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DOI：
10.1016/j.ijpharm.2008.08.022
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发表时间：
2009-01-05
影响因子：
5.8
通讯作者：
Boyd, Ben J.
中科院分区：
文献类型：
--
作者：
Lee, Kathy W. Y.;Nguyen, Tri-Hung;Boyd, Ben J.
纳米结构的基于脂质的液晶系统已被提议作为持续口服药物递送系统，但其内在释放速率、对消化过程的敏感性以及这些效应影响其体内应用的方式之间的相互作用尚不清楚。在这项研究中，两个不同的双连续立方相，制备由甘油单油酸酯和植烷三醇，和一个反向六方相形成的添加少量的维生素E植烷三醇（Q（11转基因生物）。分别制备Q（11 PHYT）和H11 PHYT+VitEA）。在体外释放实验中测定了一些分子量增加的模型亲水性药物（葡萄糖、诱惑红和FITC-clextrans）的释放动力学。在所有情况下都观察到扩散控制释放，如先前用液晶系统研究所预期的，并且发现随着基质从Q（11 GMO）变为Q（11 PHYT）再变为H-11 PHYT VitEA，每种药物的释放速率降低。然后将含有C-14-葡萄糖的制剂（用作药物释放的快速吸收标记物）经口给予大鼠，以测定不同制剂的相对体内吸收速率。结果表明，C-14-葡萄糖的吸收速率遵循在相应的体外释放研究中观察到的趋势，提供了这些材料的纳米结构可以提供定制亲水性药物在体内的吸收动力学的能力的第一个指示，并因此形成新的药物递送系统的基础。(C)2008 Elsevier B. V.保留所有权利。
Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(11 GMO). Q(11 PHYT) and H11 PHYT+VitEA, respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-clextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(11 GMO) to Q(11 PHYT) to H-11 PHYT VitEA. Formulations containing C-14-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of C-14-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system. (C) 2008 Elsevier B.V. All rights reserved.