Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, Australia.
J Control Release. 2011 Jul 30;153(2):180-6. doi: 10.1016/j.jconrel.2011.03.033. Epub 2011 Apr 8.
This study is the first to demonstrate the ability of nanostructured liquid crystal particles to sustain the absorption of a poorly water soluble drug after oral administration. Cubic (V(2)) liquid crystalline nanostructured particles (cubosomes) formed from phytantriol (PHY) were shown to sustain the absorption of cinnarizine (CZ) beyond 48h after oral administration to rats. Plasma concentrations were sustained within the range of 21.5±1.5ng/mL from 12 to 48h. In stark contrast, cubosomes prepared using glyceryl monooleate (GMO) did not sustain the absorption of CZ and drug concentrations fell below quantifiable levels after 24h. Sustained absorption of CZ from PHY cubosomes lead to a significant enhancement (p<0.05) in oral bioavailability (F%=21%) compared to a CZ suspension (9%) and oleic acid emulsion (12%). Analysis of the nanostructured particles in simulated gastric and intestinal fluids using small angle x-ray scattering (SAXS) revealed that the V(2)Pn3m nanostructure of PHY cubosomes was maintained for extended periods of time, in contrast to GMO cubosomes where the V(2)Im3m nanostructure was lost within 18h after exposure, suggesting that degradation of the LC nanostructure may limit sustained drug release. In addition, PHY cubosomes were shown to be extensively retained in the stomach (>24h) leading to the conclusion that in the case of non-digestible PHY cubosomes, the stomach may act as a non-sink reservoir that facilitates the slow release of poorly water soluble drugs, highlighting the potential use of non-digestible LC nanostructured particles as novel sustained oral drug delivery systems.
这项研究首次证明了纳米液晶颗粒能够在口服后维持难溶性药物的吸收。从植物三醇（PHY）形成的立方（V（2））液晶纳米结构颗粒（立方纳米囊）被证明能够在大鼠口服后超过 48 小时维持肉桂嗪（CZ）的吸收。从 12 到 48 小时，血浆浓度维持在 21.5±1.5ng/mL 的范围内。相比之下，使用甘油单油酸酯（GMO）制备的立方纳米囊不能维持 CZ 的吸收，并且药物浓度在 24 小时后低于可定量水平。从 PHY 立方纳米囊持续吸收 CZ 导致口服生物利用度显著提高（p<0.05）（F%=21%），与 CZ 混悬液（9%）和油酸乳液（12%）相比。使用小角 X 射线散射（SAXS）分析模拟胃和肠液中的纳米结构颗粒，发现 PHY 立方纳米囊的 V（2）Pn3m 结构在很长一段时间内得以维持，而 GMO 立方纳米囊在暴露后 18 小时内失去了 V（2）Im3m 结构，这表明 LC 纳米结构的降解可能限制了药物的持续释放。此外，PHY 立方纳米囊在胃中被广泛保留（>24 小时），这表明在不可消化的 PHY 立方纳米囊的情况下，胃可能充当非溶出性储库，有利于难溶性药物的缓慢释放，突出了不可消化的 LC 纳米结构颗粒作为新型持续口服药物递送系统的潜在用途。
