Lee Kathy W Y, Nguyen Tri-Hung, Hanley Tracey, Boyd Ben J
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
Int J Pharm. 2009 Jan 5;365(1-2):190-9. doi: 10.1016/j.ijpharm.2008.08.022. Epub 2008 Aug 26.
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(II GMO), Q(II PHYT) and H(II PHYT+VitEA), respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-dextrans) 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(II GMO) to Q(II PHYT) to H(II PHYT+VitEA). Formulations containing (14)C-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 (14)C-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.
基于纳米结构脂质的液晶体系已被提议作为口服缓释给药系统，但对于其固有释放速率、对消化过程的敏感性以及这些效应在体内应用中的影响方式之间的相互作用，人们尚未完全理解。在本研究中，制备了由单油酸甘油酯和植烷三醇形成的两种不同的双连续立方相，以及通过向植烷三醇中添加少量维生素E形成的反相六方相（分别为Q(II GMO)、Q(II PHYT)和H(II PHYT+VitEA)）。在体外释放实验中测定了多种分子量递增的模型亲水性药物（葡萄糖、诱惑红和异硫氰酸荧光素标记的葡聚糖）的释放动力学。正如先前对液晶体系的研究所预期的那样，在所有情况下均观察到扩散控制释放，并且发现随着基质从Q(II GMO)变为Q(II PHYT)再变为H(II PHYT+VitEA)，每种药物的释放速率均降低。然后将含有作为药物释放快速吸收标记物的(14)C-葡萄糖的制剂口服给予大鼠，以确定不同制剂的相对体内吸收速率。结果显示出一种趋势，即(14)C-葡萄糖的吸收速率遵循在相应体外释放研究中观察到的趋势，这首次表明这些材料的纳米结构可能具有在体内调节亲水性药物吸收动力学的能力，从而构成一种新型药物递送系统的基础。
