title: Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Otorhinolaryngology, Puerta de Hierro University Hospital, C/ Manuel de Falla, Majadahonda.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martín-Saldaña
authors.affiliation: 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.
authors.forename: Raquel
authors.initials: R
authors.lastname: Palao-Suay
authors.affiliation: Department of Otorhinolaryngology, Puerta de Hierro University Hospital, C/ Manuel de Falla, Majadahonda.
authors.forename: Almudena
authors.initials: A
authors.lastname: Trinidad
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, C/ Juan de la Cierva, Madrid, Spain. Electronic address: mraguilar@ictp.csic.es.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Aguilar
authors.affiliation: Department of Otorhinolaryngology, Puerta de Hierro University Hospital, C/ Manuel de Falla, Majadahonda; Universidad Autónoma de Madrid, Cantoblanco Campus University, Madrid.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramírez-Camacho
authors.affiliation: 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.
authors.forename: Julio
authors.initials: J
authors.lastname: San Román
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D007758:Ear, Inner / Q000187:drug effects / Q000473:pathology; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D020011:Protective Agents / Q000008:administration & dosage / Q000737:chemistry; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D020011:Protective Agents; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D002945:Cisplatin; D008775:Methylprednisolone
keywords: Cisplatin; HEI-OC1; Nanoparticles; Otoprotection; Vitamin E; α-Tocopheryl succinate