Use of mPEG-PLGA nanoparticles to improve bioactivity and hemocompatibility of streptokinase: In-vitro and in-vivo studies

摘要

Streptokinase, a clot-dissolving agent, is widely used in treatment of cardiovascular diseases such as blood clots and deep thrombosis. Streptokinase is a cost-effective drug with a short biological half-life (i.e. 15 to 30 min). In addition, due to its prokaryotic source, the immune response quickly reacts to the drug. Despite these limitations, streptokinase is still the first choice for diseases associated with thrombosis. In this work, streptokinase was encapsulated in mPEG-PLGA nanoparticles to improve its pharmacokinetic properties. The nanoparticles containing the enzyme were prepared by coaxial electrospray and their physicochemical properties, blood compatibility, circulation time and cell toxicity were evaluated. The results showed that the use of mPEG-PLGA nanoparticles to encapsulate the enzyme resulted in prolonged circulation time (up to 120 min) with a slight decrease in its activity. In vivo studies also showed that the nanoparticles containing streptokinase did not have adverse effect on blood biochemistry parameters as well as liver and kidney tissues. As a result, the mPEG-PLGA nanoparticles showed the potential for increasing the biological activity of streptokinase with no important adverse effect.