Delivering therapeutics deep into damaged tissue during bleeding is challenging because of the outward flow of blood. When coagulants cannot reach and clot blood at its source, uncontrolled bleeding can occur and increase surgical complications and fatalities. Self-propelling particles have been proposed as a strategy for transporting agents upstream through blood. Many nanoparticle and microparticle systems exhibiting autonomous or collective movement have been developed, but propulsion has not been used successfully in blood or used in vivo to transport therapeutics. We show that simple gas-generating microparticles consisting of carbonate and tranexamic acid traveled through aqueous solutions at velocities of up to 1.5 cm/s and delivered therapeutics millimeters into the vasculature of wounds. The particles transported themselves through a combination of lateral propulsion, buoyant rise, and convection. When loaded with active thrombin, these particles worked effectively as a hemostatic agent and halted severe hemorrhage in multiple animal models of intraoperative and traumatic bleeding. Many medical applications have been suggested for self-propelling particles, and the findings of this study show that the active self-fueled transport of particles can function in vivo to enhance drug delivery.
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机译:由于血液的外流,在出血过程中将治疗剂深深地输送到受损组织中具有挑战性。当凝结剂无法到达源头并凝结血液时,就会发生失控的出血并增加手术并发症和死亡人数。已经提出了自推进颗粒作为通过血液向上游输送试剂的策略。已经开发出许多表现出自主运动或集体运动的纳米粒子和微粒系统,但是推进尚未在血液中成功使用或在体内用于运输治疗剂。我们表明,由碳酸盐和氨甲环酸组成的简单的产气微粒以高达1.5 cm / s的速度通过水溶液,并向伤口的血管系统输送了毫米的治疗药物。颗粒通过侧向推进,浮力上升和对流的结合而自身运输。当负载活性凝血酶时,这些颗粒可有效用作止血剂,并在多种术中和外伤性出血动物模型中中止严重出血。已经提出了许多用于自推进颗粒的医学应用,并且该研究的结果表明,颗粒的主动自燃运输可以在体内起作用以增强药物递送。
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