Injectable glycol chitosan thermogel formulation for efficient inner ear drug delivery.

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Otolaryngology

Background:

• Inner ear drug delivery faces challenges due to the blood-labyrinth barrier.
• Dexamethasone (DEX) is a corticosteroid used for inner ear conditions, but its delivery is inefficient.
• Developing advanced carriers is crucial for effective localized inner ear treatment.

Purpose of the Study:

• To synthesize and evaluate hexanoyl glycol chitosan (HGC) as an injectable thermogel for enhanced inner ear delivery of dexamethasone (DEX).
• To characterize the physicochemical and thermogelling properties of HGC-based formulations.
• To assess the drug release kinetics, stability, and safety of the thermogel for intratympanic delivery.

Main Methods:

• Hexanoyl glycol chitosan (HGC) was synthesized and characterized.
• Amphiphilic thermogel formulations were prepared with varying DEX concentrations.
• Physicochemical properties and thermogelling behavior (Tgel ≈ 32°C) were analyzed using 1H NMR, ATR-FTIR, and rheometry.
• In vitro drug release kinetics and in vivo safety (cytotoxicity, inflammation) were evaluated.

Main Results:

• HGC formed a thermogel at approximately 32°C, suitable for injectable delivery.
• Formulations demonstrated versatile drug release profiles, ranging from hours to over two weeks.
• The HGC thermogel exhibited excellent residual stability (>21 days) in the ear.
• No cytotoxicity or inflammation was observed in the middle and inner ear tissues.
• High concentrations of DEX were successfully delivered to the inner ear.

Conclusions:

• Hexanoyl glycol chitosan (HGC) thermogel is a promising, safe, and effective carrier for intratympanic drug delivery.
• The developed formulation enhances the efficiency of inner ear drug delivery, particularly for dexamethasone.
• HGC thermogel offers a versatile platform for localized treatment of inner ear disorders.