title: Ultrasound active nanoscaled lipid formulations for thrombus lysis.
abstract: In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis.
authors.affiliation: Department of Neurosurgery, University of Marburg, Marburg, Germany. andreas.becker@staff.uni-marburg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Becker
authors.forename: Elena
authors.initials: E
authors.lastname: Marxer
authors.forename: Jana
authors.initials: J
authors.lastname: Brüssler
authors.forename: Anne Sophia
authors.initials: AS
authors.lastname: Hoormann
authors.forename: Daniela
authors.initials: D
authors.lastname: Kuhnt
authors.forename: Udo
authors.initials: U
authors.lastname: Bakowsky
authors.forename: Christopher
authors.initials: C
authors.lastname: Nimsky
mesh_terms: D004867:Equipment Design; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D020767:Intracranial Thrombosis / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D045423:Microbubbles / Q000627:therapeutic use; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D049329:Nanostructures / Q000737:chemistry*; D010743:Phospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013459:Sulfur Hexafluoride / Q000008:administration & dosage / Q000627:therapeutic use; D013499:Surface Properties; D015912:Thrombolytic Therapy / Q000379:methods; D014464:Ultrasonic Therapy / Q000379:methods; D014465:Ultrasonics
chemical_list: D005343:Fibrinolytic Agents; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride