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J Biomed Mater Res A ; 108(2): 193-200, 2020 02.
Article in English | MEDLINE | ID: mdl-31581363

ABSTRACT

Acute thrombosis, which can lead to vessel occlusion and ischemic complication, is a major cause of death and disability from myocardial infarction and stroke in recent years. Traditional drugs used in clinical thrombolytic therapy have many disadvantages, such as, higher drug dosage, shorter halftime. Thus, an efficient, safe, noninvasive, and easy thrombolysis method is urgently needed. A novel nanometer targeted carrier of a thrombolytic drug was developed in this study to improve the efficacy of thrombolytic therapy. To prepare the carrier, the carbodiimide-mediated amide was adopted to link urokinase (UK) and Arg-Gly-Asp-Ser tetrapeptide (RGDS) to the surface of the treated Bacillus amyloliquefaciens spores (BA) to synthesize UK-BA-RGDS nanoparticles. The thrombolysis rate of UK-BA-RGDS was 87%, which was nearly fivefold higher than that of commercial UK. Additionally, the tail bleeding time of UK-BA-RGDS was decreased compared with commercial UK (601 vs. 1,145 s). Furthermore, the blood flow velocity at the thrombus was recovered to ~80% of the initial state in 80 min after injection of UK-BA-RGDS. These results might indicate that the UK-BA-RGDS nanoparticles may be an effective targeted drug for the treatment of thromboembolism without hemorrhagic complication. Besides, the BA nanoparticle is a potential carrier of other drugs a wide range of possible applications.


Subject(s)
Drug Carriers/chemistry , Nanoparticles/chemistry , Thrombolytic Therapy , Urokinase-Type Plasminogen Activator/administration & dosage , Animals , Bacillus amyloliquefaciens/chemistry , Drug Delivery Systems , Male , Oligopeptides/chemistry , Rats, Wistar , Spores, Bacterial/chemistry , Urokinase-Type Plasminogen Activator/therapeutic use
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