Perlstein My, Aserin Abraham, Wachtel Ellen J, Garti Nissim
The Ratner Chair of Chemistry, Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
Weizmann Institute of Science, Department of Materials & Interfaces, Rehovot 76100, Israel.
Colloids Surf B Biointerfaces. 2015 Dec 1;136:282-90. doi: 10.1016/j.colsurfb.2015.08.044. Epub 2015 Sep 25.
Propofol (2,6-diisopropylphenol) is a drug for both induction and maintenance of anesthesia. Pure propofol cannot be injected because of its lipophilic character, low water-solubility, and low bioavailability. Presently, propofol is formulated in an unstable emulsion, easily oxidized, and easily contaminated with bacteria. We are proposing new, propofol-loaded modified microemulsions, stable thermodynamically, and microbiologically safe; the microemulsions are fully dilutable with water. Structural characterization of the empty and the propofol-loaded systems as a function of water dilution was accomplished using advanced analytical tools such as SD-NMR, SAXS, cryo-TEM, DSC, electrical conductivity, and viscosity. Upon water dilution the propofol-loaded concentrate forms swollen reverse micelles that upon further dilution (40 wt% water) progressively transform into a bicontinuous mesophase and then invert (>65 wt% water) into O/W nanodroplets without "losing" the solubilized propofol. The drug exhibits strong interactions with the surfactant (DSC and SD-NMR). Propofol increases the size of the microemulsion nanodroplets, but does not modify the microemulsion behavior. Water, ethanol, and PG are essential structural components, but do not interact directly with propofol.
丙泊酚（2,6 - 二异丙基苯酚）是一种用于诱导和维持麻醉的药物。由于其亲脂性、低水溶性和低生物利用度，纯丙泊酚不能直接注射。目前，丙泊酚是以一种不稳定的乳剂形式配制的，容易氧化且易被细菌污染。我们正在研发新型的载丙泊酚改性微乳剂，其具有热力学稳定性和微生物安全性，并且微乳剂可完全用水稀释。利用先进的分析工具，如自旋扩散核磁共振（SD - NMR）、小角X射线散射（SAXS）、冷冻透射电子显微镜（cryo - TEM）、差示扫描量热法（DSC）、电导率和粘度等，对空的和载丙泊酚体系随水稀释的结构特征进行了表征。加水稀释时，载丙泊酚浓缩物形成膨胀的反胶束，进一步稀释（40 wt%水）时逐渐转变为双连续中间相，然后反转（>65 wt%水）成水包油纳米液滴，而不会“损失”已增溶的丙泊酚。该药物与表面活性剂表现出强烈的相互作用（DSC和SD - NMR）。丙泊酚增加了微乳剂纳米液滴的尺寸，但不改变微乳剂的行为。水、乙醇和丙二醇是必不可少的结构成分，但它们不直接与丙泊酚相互作用。
