title: Propofol solubilization and structural transformations in dilutable microemulsion.
abstract: 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.
authors.affiliation: 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.
authors.forename: My
authors.initials: M
authors.lastname: Perlstein
authors.affiliation: 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.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aserin
authors.affiliation: Weizmann Institute of Science, Department of Materials & Interfaces, Rehovot 76100, Israel.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Wachtel
authors.affiliation: 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. Electronic address: garti@vms.huji.ac.il.
authors.forename: Nissim
authors.initials: N
authors.lastname: Garti
mesh_terms: D002152:Calorimetry, Differential Scanning; D004655:Emulsions; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission / Q000379:methods; D015394:Molecular Structure; D015742:Propofol / Q000737:chemistry*; D012542:Scattering, Radiation; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D004655:Emulsions; D015742:Propofol
keywords: Drug delivery; Microemulsions; Propofol; SAXS; SD-NMR