Document Type: Conference Proceedings
Department of Medical physics, Medical Sciences, Tarbiat Modares University, Tehran, Iran
Department of Medical physics, Faculty member of Medical Sciences, Tarbiat Modares University, P O Box: 14115-331, Tehran, Islamic Republic of Iran Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Department of Neurology, Firoozgar Hospital, Firoozgar Clinical Research Development Center (FCRDC), Iran University of Medical Sciences (IUMS), Tehran, Iran
Introduction: Stroke causes death and disability in patients throughout the world. At present, the only FDA- approved drug for ischemic stroke is recombinant tissue plasminogen activator (rt- PA). Unfortunately, rtPA can cause intracerebral hemorrhage and must use within limited time window (within 3-4.5 hour after onset of stroke). Ultrasound with rtPA loaded liposomes (rtPA_L) was suggested as adjuvant therapy that reduce the dose of rt-PA and increase its efficiency. Different frequency protocols such as kHz and MHz were used for sonothrombolysis. In this study, we suggested a protocol including both kHz and MHz with rtPA_L The kHz wave could fragment rtPA_Ls and release rtPA, the MHz enhances lytic efficiency of released rt-PA by stable cavitation and its microstreaming. This protocol may reduce bioeffect of ultrasound wave and simultaneously at least maintain rt-PA lytic effect.
Materials and Methods: The rt-PA loaded liposomes were prepared by hydrating lipid film with rt-PA and freezing liposomes under air pressure (4 atm). Cylindrical human whole blood clots (1 mm diameter) formed in and around micropipette at 37 ˚C. In combination with rtPA_L ([rtPA]=50 μg/ml) and human plasma, three protocol were used: 1 MHz (1.5 W/cm2_ 30 minutes), 130 kHz (
0.01 W/cm2_10 s) + 1 MHz (0.5 W/cm2_ 30 minutes) and control. Clots were imaged under microscope and clot lysis were quantified by measuring clot diameters before and after sonication.
Results: Statistical analysis of clot diameter varation between two sonication groups (1 MHz (1.5 W/cm2_ 30 minutes), 130 kHz ( 0.01 W/cm2_10 s) + 1 MHz (0.5 W/cm2_ 30 minutes)) do not show significant difference.
Conclusion: Not significant difference between two sonication groups indicates that the dual frequency protocol by using less energy and consequently lower bioeffects may have similar effect as single frequency protocol.