Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Cisplatin is a chemotherapeutic agent that causes the irreversible death of auditory sensory cells, leading to hearing loss. Local administration of cytoprotective drugs is a potentially better option co-therapy for cisplatin, but there are strong limitations due to the difficulty of accessing the i...

Descripción completa

Detalles Bibliográficos
Autores: Cervantes, Blanca, Arana Urbieta, Lide, Murillo Cuesta, Silvia, Bruno, Marina, Alcorta Calvo, Miren Itziar, Varela Nieto, Isabel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/37420
Acceso en línea:http://hdl.handle.net/10810/37420
Access Level:acceso abierto
Palabra clave:nanocarriers
dexamethasone
hydrocortisone
otic protection
stearic acid-based solid lipid nanoparticle (SLN)
sensorineural hearing-loss
intratympanic dexamethasone
drug-delivery
polymeric nanoparticles
cancer-therapy
HEI-OC1 cells
mechanisms
management
sustains
carriers
Descripción
Sumario:Cisplatin is a chemotherapeutic agent that causes the irreversible death of auditory sensory cells, leading to hearing loss. Local administration of cytoprotective drugs is a potentially better option co-therapy for cisplatin, but there are strong limitations due to the difficulty of accessing the inner ear. The use of nanocarriers for the efficient delivery of drugs to auditory cells is a novel approach for this problem. Solid lipid nanoparticles (SLNs) are biodegradable and biocompatible nanocarriers with low solubility in aqueous media. We show here that stearic acid-based SLNs have the adequate particle size, polydispersity index and zeta-potential, to be considered optimal nanocarriers for drug delivery. Stearic acid-based SLNs were loaded with the fluorescent probe rhodamine to show that they are efficiently incorporated by auditory HEI-OC1 (House Ear Institute-Organ of Corti 1) cells. SLNs were not ototoxic over a wide dose range. Glucocorticoids are used to decrease cisplatin-induced ototoxicity. Therefore, to test SLNs' drug delivery efficiency, dexamethasone and hydrocortisone were tested either alone or loaded into SLNs and tested in a cisplatin-induced ototoxicity in vitro assay. Our results indicate that the encapsulation in SLNs increases the protective effect of low doses of hydrocortisone and lengthens the survival of HEI-OC1 cells treated with cisplatin