title: Correlation of structure and echogenicity of nanoscaled ultrasound contrast agents in vitro.
abstract: Ultrasound is a common tool for clinical diagnosis due to its safety and economic. Especially the addition of ultrasound contrast agents leads to a high diagnostic reliability. In recent years ultrasound has been used as a trigger for directed drug delivery or to enhance thrombolysis. We developed a nanoscaled ultrasound contrast agent (NUSCA) to improve these applications. In the future drugs can be incorporated into this contrast agent to achieve a combination of ultrasound diagnosis and therapy. The aim of the present study is to elucidate the structure of the nanoscaled lipid formulations and a potential dependence of the ultrasound contrast enhancement on this structure. Our NUSCA is based on the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and the single-chained polyethylene glycol (40) stearate (PEG40S). In this study the effect of increasing concentrations of the single chained PEG40S on the structure of the lipid formulations was characterised using Dynamic Light Scattering, cryo-Transmission Electron Microscopy, Nuclear Magnetic Resonance spectroscopy, lipid monolayer studies and epifluorescence measurements. In addition, the ultrasound contrast enhancement for the formulations was determined in vitro. Dependence between structure and ultrasound contrast was found. All PEG40S concentrations lead to a mixture of liposomes and discoid micelles. With increasing PEG40S content the amount of micelles increased. Certain PEG40S concentrations lead to an ultrasound contrast superior to the contrast of the commercially available ultrasound contrast agent SonoVue(®).
authors.affiliation: University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: jana.bruessler@staff.uni-marburg.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Brüssler
authors.affiliation: University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Marxer
authors.affiliation: University of Marburg, Department of Neurosurgery, Baldingerstraße 1, 35033 Marburg, Germany. Electronic address: andreas.becker@Staff.Uni-Marburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.affiliation: Albert-Ludwig-University Freiburg, Institute of Pharmaceutical Science, Department of Pharmaceutical Technology and Biopharmacy, Hermann-Herder-Straße 9, 79104 Freiburg i. Brsg., Germany. Electronic address: rolf.schubert@pharmazie.uni-freiburg.de.
authors.forename: Rolf
authors.initials: R
authors.lastname: Schubert
authors.affiliation: St. Georg Hospital Eisenach, Department of Cardiovascular Medicine I, Mühlhäuser Str. 94-95, 99817 Eisenach, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Schümmelfeder
authors.affiliation: University of Marburg, Department of Neurosurgery, Baldingerstraße 1, 35033 Marburg, Germany. Electronic address: nimsky@med.uni-marburg.de.
authors.forename: Christopher
authors.initials: C
authors.lastname: Nimsky
authors.affiliation: University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany. Electronic address: ubakowsky@aol.com.
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D005453:Fluorescence; D017078:Laser-Doppler Flowmetry; D008027:Light; D008055:Lipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011312:Pressure; D012542:Scattering, Radiation; D013696:Temperature; D014465:Ultrasonics
chemical_list: D003287:Contrast Media; D008055:Lipids; D015060:1,2-Dipalmitoylphosphatidylcholine; D011092:Polyethylene Glycols
keywords: Diagnostics; Directed drug delivery; Lipid formulations; Liposomes; Micelles; Sonothrombolysis