Nanoparticle assisted drug delivery to the cytoplasm is limited by sequestration of nanoparticles in endosomes. Endosomal escape through polymer-induced membrane destabilization is one of a few well characterized mechanisms to overcome it. Aiming to utilize this method in vivo, it is necessary to understand how modulating the structural and chemical features of the polymer and the presence of proteins in biological fluids can affect this activity. Here, as a model for the endosomal membrane, we use the membrane of red blood cells evaluate the membrane destabilization ability of a model amphiphilic polymer in the presence of blood plasma using a hemolysis assay. This allows determination of red blood cells membrane permeabilization through the quantification of hemoglobin leakage. Our results showed a strong inhibitory effect of plasma, and that hemolytic activity can be improved by chemical modification of the polymeric micelle, reducing its interaction with plasma proteins. Finally, a second mechanism of pH-induced direct diffusion is proposed and tested using an oil/water partitioning model. These results offer a body of knowledge to improve delivery of drugs across biological membranes using carefully designed polymeric nanocarriers.

纳米颗粒辅助药物递送至细胞质受到内体中纳米颗粒的隔离的限制。通过聚合物诱导的膜去稳定作用进行的内体逸出是克服它的一些特征良好的机制之一。旨在在体内利用这种方法，有必要了解调节聚合物的结构和化学特征以及生物流体中蛋白质的存在如何影响这种活性。在这里，作为内体膜的模型，我们使用红细胞膜通过溶血分析评估存在血浆的模型两亲性聚合物的膜去稳定能力。这可以通过定量血红蛋白渗漏来确定红细胞膜通透性。我们的结果显示了对血浆的强抑制作用，并且溶血活性可以通过化学修饰高分子胶束来改善，从而减少其与血浆蛋白的相互作用。最后，提出了pH诱导的直接扩散的第二种机理，并使用油/水分配模型进行了测试。