Advanced delivery systems for sodium thiosulfate in cisplatin otoprotection

Cisplatin is an indispensable agent in pediatric oncology, yet its clinical utility is severely compromised by irreversible sensorineural hearing loss, which affects up to 60 % of young patients. Sodium thiosulfate (STS) has recently emerged as the gold-standard otoprotectant, but its systemic administration is constrained by a critical pharmacokinetic paradox: a mandatory 6-hour delay after cisplatin infusion is required to avoid interference with antitumor efficacy, creating a window of vulnerability during which the inner ear remains unprotected. This review systematically examines the engineering strategies developed to overcome the limitations of systemic STS delivery, with a focus on nanotechnology platforms and localized routes of administration. We highlight how the shift from systemic to intratympanic delivery enables high intracochlear concentrations of STS without compromising the antineoplastic action of cisplatin. Key innovations include: (i) lipid- and polymer-based nanoparticle systems that optimize transport across the round window membrane; (ii) in situ-forming hydrogels and microgels that resist Eustachian tube clearance through bioadhesion and provide sustained STS release; and (iii) noninvasive transtympanic strategies that use chemical permeation enhancers to bypass the tympanic membrane, transfer through the walls of the tympanic cavity. The synergy of stimuli-responsive nanocarriers and localized delivery protocols represents a transformative approach to otoprotection, offering the prospect of hearing preservation precisely during peak cochlear cisplatin exposure and thereby improving the quality of life for childhood cancer survivors.