Abstract
Cisplatin (cis-diamminedichloroplatinum) is widely used as a chemotherapeutic drug for genitourinary, breast, lung and head and neck cancers. Though effective in inducing apoptosis in cancer cells, cisplatin treatment causes severe hearing loss among patients. Steroids have been shown to mitigate cisplatin-induced hearing loss. However, steroids may interfere with the anti-cancer properties of cisplatin if administered systemically, or are rapidly cleared from the middle and inner ear and hence lack effectiveness when administered intra-tympanically. In this work, we deliver prednisolone-loaded nanoparticles magnetically to the cochlea of cisplatin-treated mice. This magnetic delivery method substantially reduced hearing loss in treated animals at high frequency compared to control animals or animals that received intra-tympanic methylprednisolone. The method also protected the outer hair cells from cisplatin-mediated ototoxicity.
Highlights
IntroductionCisplatin (cis-diamminedichloroplatinum) and other platinum based drugs are the antineoplastic drugs of choice for various genitourinary cancers, certain forms of breast cancers, and as radiosensitizers for most head and neck cancers
Cisplatin and other platinum based drugs are the antineoplastic drugs of choice for various genitourinary cancers, certain forms of breast cancers, and as radiosensitizers for most head and neck cancers
We show that magnetic steroid delivery to the inner ear can be used to protect hearing in mice receiving systemic cisplatin regimens
Summary
Cisplatin (cis-diamminedichloroplatinum) and other platinum based drugs are the antineoplastic drugs of choice for various genitourinary cancers, certain forms of breast cancers, and as radiosensitizers for most head and neck cancers. The ototoxic effect of cisplatin is noticeable, with hearing loss within hours or days after the first cisplatin injection (Rybak et al, 2009). It is cumulative, and the cumulative effect implies particular vulnerability in pediatric populations as repeated treatments, even separated by years, eventually lead to complete hearing loss, which may in turn lead to pervasive developmental delays including speech, cognitive and social developmental challenges
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