Department of Otorhinolaryngology, Puerta de Hierro University Hospital, C/ Manuel de Falla, Majadahonda.
Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/ Juan de la Cierva, Madrid, Spain; Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Spain.
Nanomedicine. 2016 May;12(4):965-976. doi: 10.1016/j.nano.2015.12.367. Epub 2015 Dec 28.
6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found.
Cisplatin is a commonly used chemotherapeutic agent against many cancers clinically. However, one of the significant side-effects remains ototoxicity. Here, the authors presented their data on using 6α-methylprednisolone-loaded nanoparticles in the reduction of ototoxicity in in-vitro and in-vivo experiments. Early promising results should enable further refinement of adopting this new approach in future experiments.
已开发载有 6α-甲基强的松龙的无表面活性剂纳米颗粒来缓解顺铂耳毒性。纳米颗粒基于两种不同的两亲性伪嵌段共聚物，通过自由基聚合得到，基于 N-乙烯基吡咯烷酮和α-生育酚琥珀酸酯或α-生育酚的甲基丙烯酸衍生物。共聚物通过在水介质中的胶束沉淀形成能够将 6α-甲基强的松龙包封在其内核中的球形纳米颗粒。所获得的纳米载体在 HEI-OC1 细胞中进行了体外测试，并在小鼠模型中进行了体内测试。未负载的纳米颗粒不能显著降低顺铂的耳毒性。载有纳米颗粒的纳米颗粒降低了顺铂的耳毒性，基于维生素 E 的甲基丙烯酸衍生物的纳米颗粒更具活性，因为其包封效率更高。这种配方能够保护耳蜗底部的毛细胞，在小鼠模型中测试的最高频率上具有积极的影响。在体外和体内实验之间发现了良好的相关性。
顺铂是临床上对抗多种癌症的常用化疗药物。然而，一个显著的副作用仍然是耳毒性。在这里，作者在体外和体内实验中展示了使用载有 6α-甲基强的松龙的纳米颗粒减少耳毒性的数据。早期的有希望的结果应该能够使进一步改进在未来的实验中采用这种新方法。
