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Título

pH-sensitive polymeric nanoparticles with antioxidant and anti-inflammatory properties against cisplatin-induced hearing loss

AutorMartín-Saldaña, Sergio; Palao-Suay, Raquel; Aguilar, María Rosa ; García-Fernández, Luis ; Arévalo, Humberto; Trinidad, Almudena; Ramírez-Camacho, Rafael; San Román, Julio
Palabras claveAnti-inflammatory
Ibuprofen
Ototoxicity
Nanoparticles
Dexamethasone
Antioxidant
Fecha de publicación2018
EditorElsevier
CitaciónJournal of controlled release : official journal of the Controlled Release Society 270: 53-64 (2018)
ResumenPolymeric nanoparticles (NPs) based on smart synthetic amphiphilic copolymers are used to transport and controlled release dexamethasone in the inner ear to protect against the ototoxic effect of cisplatin. The NPs were based on a mixture of two pseudo-block polymer drugs obtained by free radical polymerization: poly(VI-co-HEI) and poly(VP-co-MVE) or poly(VP-co-MTOS), being VI 1-vinylimidazole, VP N-vinylpyrrolidone, and HEI, MVE and MTOS the methacrylic derivatives of ibuprofen, α-tocopherol and α-tocopheryl succinate, respectively. The NPs were obtained by nanoprecipitation with appropriate hydrodynamic properties, and isoelectric points that matched the pH of inflamed tissue. The NPs were tested both in vitro (using HEI-OC1 cells) and in vivo (using a murine model) with good results. Although the concentration of dexamethasone administered in the NPs is around two orders of magnitude lower that the conventional treatment for intratympanic administration, the NPs protected from the cytotoxic effect of cisplatin when the combination of the appropriate properties in terms of size, zeta potential, encapsulation efficiency and isoelectric point were achieved. To the best of our knowledge this is the first time that pH sensitive NPs are used to protect from cisplatin-induced hearing loss by intratympanic administration.
URIhttp://hdl.handle.net/10261/161021
Identificadoresdoi: 10.1016/j.jconrel.2017.11.032
issn: 0168-3659
e-issn: 1873-4995
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