Ultrasound-triggered thrombolysis using urokinase-loaded nanogels

To find a way to modulate the effect of thrombolytic proteins by increasing their specificity, minimizing their adverse effect as well as lengthening their circulation time for the treatment of ischemic vascular disease holds great promise. In this work, urokinase-type plasminogen activator (uPA) was encapsulated into hollow nanogels which are generated by the reaction of glycol chitosan and aldehyde capped poly(ethylene glycol) (OHC-PEG-CHO) through a one-step approach of ultrasonic spray. The uPA-loaded nanogels, with size of 200-300 nm, have longer circulation time than that of the nude urokinase in vivo, besides the protein can be triggered to release in faster rate under diagnostic ultrasonic condition of 2 MHz, which significantly enhanced the thrombolysis of clots. The results are promising for increasing the specificity and positive effects of thrombolytic agents like recombinant tissue plasminogen activator (rt-PA) for the current treatment of ischemic vascular disease. (C) 2012 Elsevier B.V. All rights reserved.