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 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 cisplatinB.C. was supported by an MSC postdoctoral contract, FP7-PEOPLE2013-IAPP TARGEAR. This work was supported by grants MINECO/FEDER (SAF2017-86107-R) and Comunidad de Madrid/FEDER MULTITARGET& VIEW-CM (B2017/BMD-3688) to I.V.N. and ELKARTEK (2017 KK-2017/00008) to I.A