Abstract
Current tissue plasminogen-based therapeutic strategies for stroke suffer from systemic side effects and poor efficacy. Hence, novel drug delivery methods are needed to overcome these shortcomings. Exosome-based drug formulations have been shown to have superior therapeutic outcomes compared to conventional systemic drug delivery approaches. In this paper, we report exosome surface-coated tissue plasminogen activator (tPA)/catalase nanoformulations with improved thrombolytic efficacy compared to free tPA, which also reduce side effects. The results showed that the tPA exosome formulations retained tPA activity, improved tPA stability, exhibited significant fibrinolysis, and showed no significant toxicity effects. Further, when combined with antioxidant enzyme catalase, the formulation was able to inhibit hydrogen peroxide-mediated oxidative stress and toxicity. Hence, exosome-based tPA/catalase nanoformulations could have the potential to offer a safer and effective thrombolytic therapy.