Optimized phospholipid-based nanoparticles for inner ear drug delivery and therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Otolaryngology
• Pharmacology

Background:

• Efficient inner ear drug delivery remains a challenge for treating hearing loss and other auditory disorders.
• Current treatments often lack targeted delivery and sustained release, leading to suboptimal therapeutic outcomes.
• Phospholipid-based nanoparticles offer a promising platform for enhanced drug delivery systems.

Purpose of the Study:

• To develop and evaluate novel phospholipid-based nanoparticles for efficient inner ear drug delivery.
• To investigate the role of nanoparticle surface properties on drug penetration, distribution, and therapeutic efficacy.
• To establish an in vitro screening system for optimizing inner ear drug delivery carriers.

Main Methods:

• Preparation and characterization of four types of phospholipid nanoparticles (neutral, anionic, cationic, cationic-PEG) with varying surface properties.
• In vitro assessment of nanoparticle penetration through an artificial mucosa model and cellular uptake by HEI-OC1 cells.
• Ex vivo evaluation of particle movement in organotypic cultures of the organ of Corti.
• In vivo studies in mice involving intratympanic injection of dexamethasone-loaded nanoparticles, biodistribution analysis, and assessment of therapeutic efficacy in an ototoxicity model using auditory brainstem response (ABR) tests and quantitative PCR for cytokine levels.

Main Results:

• Nanoparticles, approximately 200 nm in diameter, exhibited distinct zeta potentials influencing their behavior.
• Cationic-PEG nanoparticles showed optimal penetration and cellular uptake in the in vitro model.
• In vivo studies demonstrated that dexamethasone-loaded nanoparticles significantly improved hearing loss recovery and reduced pro-inflammatory cytokines compared to conventional dexamethasone sodium phosphate (Dex-SP) solution.
• Nanoparticle surface properties critically influenced intratympanic injection, penetration, and distribution.

Conclusions:

• Phospholipid nanoparticles, particularly cationic-PEG variants, represent a promising drug delivery system for the inner ear.
• The developed in vitro artificial mucosa model is valuable for screening and optimizing inner ear drug delivery carriers.
• Surface modification of nanoparticles is crucial for enhancing drug delivery efficiency and therapeutic outcomes in inner ear treatments.