Laboratory of Analytical Chemistry, Department of Chemistry, 00014 University of Helsinki, Finland.
Eur J Pharm Sci. 2010 Nov 20;41(3-4):515-22. doi: 10.1016/j.ejps.2010.08.006. Epub 2010 Aug 24.
Fatal drug overdoses are a cause for concern all over the world. We present here a lipid-based formulation which has a strong affinity for some common illicit street drugs and can be used in vivo as a lipid 'sink'. In this study, the in vitro interactions of nine lipophilic drugs and three lipid dispersions were determined by electrokinetic capillary chromatography and fluorescence polarization. Two lipid dispersions, zwitterionic 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and an anionic mixture of POPC and 1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) were tested and compared with a commercial lipid dispersion Intralipid(®), which has been successfully used for resuscitation of patients in cases of anesthetic overdoses. The interactions between dispersions and the drugs were quantified by means of retention factors and distribution constants, which makes the results highly comparable to those obtained from any other formulation of lipids. The results demonstrate a stronger interaction between the drugs and an artificial liposome dispersion than with the commercial Intralipid dispersion. The liposome dispersion composed of POPC and POPG functions as a lipid 'sink' for efficient entrapment of various lipophilic drugs.
致命的药物过量是全世界都关注的问题。我们在这里展示了一种基于脂质的制剂，它对一些常见的非法街头毒品具有很强的亲和力，可以在体内用作脂质“陷阱”。在这项研究中，通过动电毛细管色谱法和荧光偏振法测定了九种亲脂性药物和三种脂质分散体的体外相互作用。两种脂质分散体，即两性离子 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）和 POPC 与 1-棕榈酰基-2-油酰基-sn-甘油-3-[磷酸-rac-（1-甘油）]（POPG）的混合物与商业脂质分散体 Intralipid(®)进行了测试和比较，Intralipid(®)已成功用于麻醉过量患者的复苏。通过保留因子和分配常数定量测定了分散体与药物之间的相互作用，这使得结果与任何其他脂质制剂的结果高度可比。结果表明，药物与人工脂质体分散体之间的相互作用强于与商业 Intralipid 分散体之间的相互作用。由 POPC 和 POPG 组成的脂质体分散体可作为脂质“陷阱”，有效捕获各种亲脂性药物。
