کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2946181 1577181 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A New Drug Delivery System for Intravenous Coronary Thrombolysis With Thrombus Targeting and Stealth Activity Recoverable by Ultrasound
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
A New Drug Delivery System for Intravenous Coronary Thrombolysis With Thrombus Targeting and Stealth Activity Recoverable by Ultrasound
چکیده انگلیسی

ObjectivesThe purpose of this study was to develop a new intelligent drug delivery system for intracoronary thrombolysis with a strong thrombolytic effect without increasing bleeding risk.BackgroundRapid recanalization of an occluded coronary artery is essential for better outcomes in acute myocardial infarction. Catheter-based recanalization is widely accepted, but it takes time to transport patients. Although the current fibrinolytic therapy can be started quickly, it cannot achieve a high reperfusion rate. Recently, we generated nanoparticles comprising tissue-type plasminogen activator (tPA), basic gelatin, and zinc ions, which suppress tPA activity by 50% with 100% recovery by ultrasound (US) in vitro.MethodsThe thrombus-targeting property of nanoparticles was examined by an in vitro binding assay with von Wilbrand factor and with a mouse arterial thrombosis model in vivo. The thrombolytic efficacy of nanoparticles was evaluated with a swine acute myocardial infarction model.ResultsNanoparticles bound to von Wilbrand factor in vitro and preferentially accumulated at the site of thrombus in a mouse model. In a swine acute myocardial infarction model, plasma tPA activity after intravenous injection of nanoparticles was approximately 25% of tPA alone and was recovered completely by transthoracic US (1.0 MHz, 1.0 W/cm2). During US application, plasma tPA activity near the affected coronary artery was recovered and was higher than that near the femoral artery. Although treatment with tPA alone (55,000 IU/kg) recanalized the occluded coronary artery in only 1 of 10 swine, nanoparticles containing the same dose of tPA with US achieved recanalization in 9 of 10 swine within 30 min.ConclusionsWe developed an intelligent drug delivery system with promising potential for better intravenous coronary thrombolysis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the American College of Cardiology - Volume 60, Issue 24, 18 December 2012, Pages 2550–2557
نویسندگان
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