Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, 3052, VIC, Australia.
Drug Deliv Transl Res. 2011 Dec;1(6):429-38. doi: 10.1007/s13346-011-0045-z.
Reverse hexagonal (H2) liquid crystals formed from selachyl alcohol were demonstrated to sustain the absorption of the poorly water-soluble drug cinnarizine (CZ) after oral administration to rats. When CZ was administered as a bolus lipid solution in selachyl alcohol, the T max was observed to be 23.5 ± 5.9 h, significantly longer than the control suspension (1 h). Administration of selachyl alcohol as dispersed nanoparticles (hexosomes) also resulted in a sustained plasma profile, with drug concentrations maintained from 20 to 40 ng/mL over the first 24 h after administration. Sustained absorption of CZ from the selachyl alcohol hexosomes led to a significant enhancement (p < 0.05) in oral bioavailability (F% = 17%) compared to the control CZ suspension (9%). Analysis of selachyl alcohol hexosomes using small-angle x-ray scattering indicated that neither the presence of CZ (7 mg/g) nor simulated intestinal fluid altered the H2 nanostructure. Selachyl alcohol is not susceptible to digestion. Prolonged absorption from the selachyl alcohol-based H2 systems was attributed to the non-digestible nature of the lipid, similar to non-digestible phytantriol cubic (V2) systems previously reported. Furthermore, the likely presence of non-sink conditions in the gastric compartment provides a drug reservoir requiring gastric emptying to stimulate drug release from the formulation. This study highlights the potential use of non-digestible liquid crystalline systems generally and nanostructured liquid crystalline particles in particular as novel sustained oral drug delivery systems.
鲨鱼肝醇形成的反六角（H2）液晶被证明可以在大鼠口服后吸收吸收不良的水药物肉桂嗪（CZ）。当 CZ 作为鲨鱼肝醇中的脂质溶液大丸给药时，T max 观察到为 23.5 ± 5.9 h，明显长于对照悬浮液（1 h）。鲨鱼肝醇作为分散的纳米颗粒（hexosomes）给药也导致了持续的血浆曲线，药物浓度在给药后 24 h 内保持在 20 至 40 ng / mL 之间。CZ 从鲨鱼肝醇 hexosomes 中的持续吸收导致口服生物利用度（F％）显著提高（p <0.05），与对照 CZ 悬浮液（9％）相比。使用小角度 X 射线散射分析鲨鱼肝醇 hexosomes 表明，CZ 的存在（7 mg / g）或模拟肠液都不会改变 H2 纳米结构。鲨鱼肝醇不易消化。基于鲨鱼肝醇的 H2 系统的延长吸收归因于脂质的不可消化性质，类似于先前报道的不可消化植烷三醇立方（V2）系统。此外，胃腔中可能存在非吸收性条件，为药物提供了一个储库，需要排空胃以刺激从制剂中释放药物。这项研究强调了不可消化的液晶系统一般和纳米结构液晶颗粒特别是作为新型持续口服药物递送系统的潜在用途。
