Date of Award
Summer 8-18-2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biomedical Engineering
First Advisor
Amit Joshi
Second Advisor
Bing Yu
Third Advisor
Said Audi
Abstract
Cisplatin is a widely used chemotherapy drug associated with a high incidence of hearing loss, particularly in younger patients. This ototoxicity is linked to the drug’s long-term accumulation in the cochlea, where it can persist for years following treatment. Current clinical interventions, such as sodium thiosulfate (STS), offer partial protection against hearing loss but are limited by poor drug penetration into the inner ear. The objective of this study was to develop and evaluate a targeted drug delivery platform capable of overcoming anatomical and physiological barriers to reach the cochlea more effectively. Specifically, we aimed to design cationic liposome nanoparticles optimized for inner ear delivery via the transtympanic route. We hypothesized that cationic liposomes, engineered with favorable size, surface charge, and lipid composition, would enable enhanced permeability across the round window membrane, resulting in more efficient delivery of STS to the inner ear compared to free drug. To test this, we conducted both in vitro and in vivo experiments. In vitro studies using fluorescently labeled liposomes confirmed successful cellular uptake and intracellular release of encapsulated cargo. In vivo studies in chinchilla models revealed that both liposomal STS and free STS were able to reach the cochlea. Notably, liposomal STS achieved greater delivery efficiency from the middle ear to the inner ear compared to free STS. Additionally, liposomal treatment resulted in no detectable systemic exposure. These findings support the feasibility of using liposomal carriers for targeted inner ear drug delivery and provide a foundation for further optimization and therapeutic validation in ototoxicity models.