Crosslinked-hybrid nanoparticle embedded in thermogel for sustained co-delivery to inner ear

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Ototoxicity Research

Background:

• Treatment-induced ototoxicity and hearing loss are significant concerns with chemotherapy and antibiotics.
• Local delivery to the inner ear is desirable for prophylactic or early treatment of ototoxicity.

Purpose of the Study:

• To investigate a novel intratympanically delivered, sustained nanoformulation for treating drug-induced ototoxicity.
• To evaluate the co-delivery of Flunarizine (FL) and Honokiol (HK) in a thermoresponsive hydrogel for ototoxicity protection.

Main Methods:

• Synthesized FL- and HK-loaded crosslinked hybrid nanoparticles (cHy-NPs) using a Quality-by-Design approach (DoE-CCD).
• Assessed cytoprotective effects in HEI-OC1 cells and in vivo zebrafish models against cisplatin.
• Developed a final nanoformulation by embedding cHy-NPs in a thermogel hydrogel and characterized its stability and drug release.

Main Results:

• FL and HK combination demonstrated enhanced cytotoxic protective effects.
• Successfully synthesized stable nanoparticles with high encapsulation efficiency and loading.
• The nanoformulation significantly reduced caspase 3/7 activation in vitro and protected neuromast hair cells in vivo.
• The thermogel formulation provided sustained release of FL and HK for at least one month.

Conclusions:

• A stable, novel nanoformulation embedded in a thermogel was successfully developed for local inner ear delivery.
• This formulation shows potential for combating treatment-induced or drug-induced ototoxicity.
• Co-delivery of FL and HK via cHy-NPs in a thermogel offers a promising strategy for ototoxicity prevention.