Resveratrol-loaded nanocarriers: formulation, optimization, characterization and in vitro toxicity on cochlear cells

Area of Science:

• Nanotechnology
• Pharmaceutics
• Oto-oncology

Background:

• Cochlear cell drug delivery presents challenges.
• Resveratrol (RES) possesses antioxidant properties beneficial for otoprotection.
• Polymeric nanoparticles offer a potential delivery vehicle for RES.

Purpose of the Study:

• To investigate the suitability of resveratrol-loaded polymeric nanoparticles (NPs) for cochlear cell drug delivery.
• To optimize NP formulation and assess physicochemical stability during freeze-drying.
• To evaluate the in vitro toxicity of RES-loaded NPs on cochlear cell lines.

Main Methods:

• Resveratrol-loaded NPs prepared via solvent-diffusion method without surfactant.
• Box-Behnken design employed for formulation optimization (PMD, PDI, ζ, EE%, Sf/Si).
• Physicochemical stability assessed with cryoprotectants (lactose, mannitol, sucrose, trehalose).
• Characterization by PXRD, in vitro drug release, and in vitro cytotoxicity assays on HEI-OC1 and SVK-1 cells.

Main Results:

• Optimal formulation achieved high desirability (0.86) with specific PMD, PDI, ζ, EE%, and Sf/Si values.
• Trehalose at >15% (w/v) was crucial for maintaining NP size and PDI stability post-freeze-drying.
• Blank NPs showed minimal toxicity (<600μg/mL), while native RES exhibited significant cytotoxicity (>50μM).

Conclusions:

• Resveratrol-loaded polymeric NPs are a suitable template for cochlear antioxidant delivery.
• The developed NPs demonstrate good physicochemical properties and stability.
• This approach holds potential for otoprotection, with NPs showing lower toxicity than native resveratrol.