Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
Int J Pharm. 2013 Aug 16;452(1-2):270-5. doi: 10.1016/j.ijpharm.2013.05.047. Epub 2013 May 29.
We demonstrate a rapidly formed cubic liquid crystalline phase, i.e. typically 1g cubic phase in less than 1 min confirmed by X-ray diffraction, consisting of an ether lipid, 1-glyceryl monooleyl ether (GME), an aprotic solvent (propylene glycol or pentane-1,5-diol) and water. The efficacy of the cubic formulation was tested in vivo by administrating formulations containing 3% (w/w) of the HCl salts of δ-aminolevulinic acid (ALA) or methylaminolevulinate (MAL) to hairless mice. The endogenous formation of protoporphyrin IX (PpIX) was monitored spectrophotometrically as a marker for cellular uptake of active compound. As reference, a commercial product containing 16% (w/w) MAL in an oil-in-water emulsion (Metvix(®)), and a cubic phase based on an ester lipid (glyceryl monooleate, GMO), previously shown to facilitate topical delivery of both ALA and MAL, were applied. It was found that in general the cubic phases gave rise to higher fluorescence levels than the mice exposed to the commercial product. The instantly formed cubic formulations based on GME demonstrated the same efficiency as the GMO based formulations. The results imply that instantly formed cubic formulations opens up new opportunities, particularly for transdermal drug delivery of substances subject to stability problems in, e.g. aqueous environments.
我们展示了一种快速形成的立方液晶相，即通过 X 射线衍射确认的典型 1g 立方相，在不到 1 分钟内形成，由醚脂质 1-甘油单油酸酯（GME）、非质子溶剂（丙二醇或戊烷-1,5-二醇）和水组成。该立方制剂的功效通过向无毛小鼠施用含有 3%（w/w）盐酸盐 δ-氨基酮戊酸（ALA）或甲氨基酮戊酸（MAL）的制剂在体内进行了测试。内源性原卟啉 IX（PpIX）的形成通过分光光度法作为细胞摄取活性化合物的标志物进行监测。作为参考，应用了一种含有 16%（w/w）MAL 的油包水乳液（Metvix®）的商业产品，以及一种先前已显示可促进 ALA 和 MAL 局部递送的基于酯脂质（单油酸甘油酯，GMO）的立方相。结果发现，一般来说，立方相产生的荧光水平高于暴露于商业产品的小鼠。基于 GME 的即刻形成的立方制剂表现出与基于 GMO 的制剂相同的效率。结果表明，即刻形成的立方制剂为药物输送开辟了新的机会，特别是对于在例如水环境中存在稳定性问题的物质的透皮药物输送。
