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

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.

Extracellular micro/nanovesicles rescue kidney from ischemia-reperfusion injury.

Acute renal failure (ARF) is a clinical challenge that is highly resistant to treatment, and its high rate of mortality is alarming. Ischemia-reperfusion injury (IRI) is the most common cause of ARF. Especially IRI is implicated in kidney transplantation and can determine graft survival. Although the exact pathophysiology of renal IRI is unknown, the role of inflammatory responses has been elucidated. Because mesenchymal stromal cells (MSCs) have strong immunomodulatory properties, they are under extensive investigation as a therapeutic modality for renal IRI. Extracellular vesicles (EVs) play an integral role in cell-to-cell communication. Because the regenerative potential of the MSCs can be recapitulated by their EVs, the therapeutic appeal of MSC-derived EVs has dramatically increased in the past decade. Higher safety profile and ease of preservation without losing function are other advantages of EVs compared with their producing cells. In the current review, the preliminary results and potential of MSC-derived EVs to alleviate kidney IRI are summarized. We might be heading toward a cell-free approach to treat renal IRI.