A novel drug delivery system may prevent hearing damage during cancer treatment by transporting medications to the inner ear which protect it during chemotherapy, its developers claim.
Researchers said the chemotherapy drug cisplatin was a lifesaver for many adults and children diagnosed with cancer but one side-effect was that it often caused hearing loss, especially in children, most of whom faced hearing loss after receiving cisplatin.
They said that in future their treatment may also be useful for noise-induced and age-related hearing loss.
University of Oklahoma assistant professor in the College of Pharmacy Dr Vibhuti Agrahari created a system that transports medications to the inner ear where they stand guard as cisplatin approaches.
The medications block calcium, which is known to damage the inner ear hair cells, or are antioxidants which protect hair cells and maintain the delicate homeostasis of the inner ear.
The hydrogel drug delivery system is injected into the ear as a liquid and turns into a gel when it encounters the body’s temperature. Within the hydrogel are nanoparticles that carry the drugs and slowly release them.
Although the research is in its early stages, Dr Agrahari said it had already shown positive results, for the delivery system and the drugs’ ability to prevent damage that leads to hearing loss. US patents have been filed for the majority of the research.
“This is a small area of study that has a lot of potential,” she said.
“Cisplatin is an important, lifesaving drug that we need for the treatment of cancer but hearing loss affects quality of life, as well as the developmental process for children, up to 90% of whom face hearing loss after receiving this type of chemotherapy. It is important that we devise a solution that prevents the damage from occurring.
“When a patient receives cisplatin, the drug quickly finds its way to the cochlea and is retained for months in the cochlea, where it damages the tiny hair cells that play a critical role in the brain’s ability to interpret sound.
“Once the hair cells are damaged, they never regenerate and hearing begins to wane. The effect is especially pronounced in children.
“To treat this type of hearing loss, we really wanted to focus on a prophylactic cure – giving the medications before the chemotherapy begins. We wanted to create a targeted drug delivery approach that can be given directly into the inner ear, rather than an oral drug that must travel throughout the body.
“The problem is especially significant in young children being treated for cancer because they are undergoing so much learning and cognitive development.”
Hydrogel injection
The research team considered the route and the obstacles the drug transporter would take.
The vehicle portion of the system comprises hydrogels, water-based substances that can change structure based on their environment. The hydrogel begins as a liquid so it can be given via an injection but once it encounters the body’s temperature, it turns into a gel.
The hydrogel is compatible with the human body so the immune system won’t reject it.
Within the hydrogel are nanoparticles that carry the drugs. The small size enables the nanoparticles to cross the basilar membrane on the way to the cochlea. Once they reach their destination, the environment of the cochlea prompts release of the drugs and because the nanoparticles are within the hydrogel, they discharge slowly, like an extended-release drug.
The gel also prevents nanoparticles from sliding into the eustachian tube.
Dr Agrahari has studied several drugs in the delivery system. Some block calcium, which is known to damage the inner ear hair cells, and others are antioxidants, which protect the hair cells and maintain the delicate homeostasis of the inner ear.
Using mathematical modelling software, the research team chose several configurations of drug amounts and formulation sizes.
Researchers tested the drug delivery system in the laboratory using inner ear cell lines. The approach is now being tested in animal models with collaborators at Hough Ear Institute in Oklahoma City.
Studies about the innovation are published in two journals.
“Overall, a novel NanoSensoGel formulation developed in this study has demonstrated its great potential in delivering therapeutics in the inner ear for prophylactic treatment of cisplatin-induced ototocity (CIO), and associated hearing loss,” the researchers reported in the Journal of Controlled Release in April 2024.
Another study reported in the Journal of Nanobiotechnology on 13 August 2024 discussed inner-ear targeted sustained drug release crosslinked hybrid nanoparticles embedded in thermoresponsive hydrogel for prophylactic cure and prevention against drug-induced or treatment-induced ototoxicity.
“These outcomes clearly suggest that the intratympanically delivered crosslinked hybrid nanoformulation developed here may serve as a promising platform to protect the inner ear hair cells not only from the cytotoxic environment of the ototoxic drugs but can also be used for noise-induced and age-related hearing loss,” they said.
“However, these remain to be elucidated in future in vivo investigations to confirm the therapeutic efficacy and translational challenges of the developed novel formulation.”
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