Preparation and Properties of Thrombus-Targeted Urokinase/Multi-Walled Carbon Nanotubes (MWCNTs)-Chitosan (CS)-RGD Drug Delivery System

• DOI: 10.1166/jbn.2021.3113
• Publication Date: 2021-10-24T04:35:17Z
• Authors: Ru Zhang; Shang Luo; Lin-Kun Hao; Yun-Ying Jiang; Ying Gao; Ning-Ning Zhang; Xue-Cheng Zhang; Yi-Min Song
• Keywords: 0301 basic medicine; Chitosan; 03 medical and health sciences; Drug Delivery Systems; Nanotubes, Carbon; Animals; Thrombosis; Rabbits; Oligopeptides; Urokinase-Type Plasminogen Activator; 3. Good health

In order to improve the therapeutic effect, prolong the action time and reduce the side effects of the first generation thrombolytic drug urokinase (UK), a novel UK/multi-walled carbon nanotubes (MWCNTs)-chitosan (CS)-arginine-glycine-aspartic acid (Arg-Gly-Asp) (RGD) drug delivery system was synthesized by chemical bonding/non covalent bond modification/ultrasonic dispersion. The results showed that the diameter of the UK/MWCNTs-CS-RGD drug delivery system was about 30–40 nm, there was a layer of UK was attached to the surface of the tube wall, and the distribution was relatively uniform. The average encapsulation efficiency was 83.10%, and the average drug loading was 12.81%. Interestingly, it also had a certain sustained-release effect, and its release law was best fitted by first-order kinetic equation. Moreover, the accelerated and long-term stability test results show that it had good stability. Compared with free UK, UK/MWCNTs-CS-RGD had thrombolytic effect in vitro. In addition, MTT experiment showed that the prepared MWCNTs-CS-RGD nanomaterials had good biocompatibility. A rabbit model of carotid artery thrombosis was used to conduct targeted thrombolysis experiments in vivo. Compared with free UK, UK/MWCNTs-CS-RGD could be enriched in the thrombosis site to achieve thrombus targeting. UK/MWCNTs-CS-RGD drug delivery system was expected to become an effective thrombolytic drug for targeted therapy of thrombosis.