Injectable polyplex-loaded glycol chitosan thermogel for efficient and safe inner ear gene delivery

Area of Science:

• Biomedical Engineering
• Gene Therapy
• Otolaryngology

Background:

• Inner ear disorders like hearing loss require effective gene delivery methods.
• Current gene delivery systems face challenges in precision and efficiency for the inner ear.

Purpose of the Study:

• To develop and evaluate a dual-component gene delivery system for inner ear disorders.
• To enhance gene delivery efficiency and therapeutic outcomes using RH-PAMAM G2 dendrimer polyplexes and hexanoyl glycol chitosan (HGC) thermogel.

Main Methods:

• RH-PAMAM G2 dendrimers modified with histidine and arginine were used to form polyplexes with plasmid DNA (pDNA).
• These polyplexes were encapsulated within an injectable HGC thermogel for sustained release.
• In vitro studies assessed DNA binding, cytotoxicity, and cellular uptake in HEI-OC1 auditory cells.
• In vivo studies in a mouse model evaluated gene expression in cochlear tissues after intratympanic administration.

Main Results:

• RH-PAMAM G2 polyplexes showed high DNA binding, low cytotoxicity, and effective transfection in auditory cells.
• The HGC thermogel provided a protective matrix for sustained gene release and prevented premature clearance.
• In vivo studies demonstrated substantial gene expression in key cochlear regions, including the spiral ganglion and organ of Corti.
• The HGC thermogel exhibited excellent biocompatibility, with no observed inflammation or adverse effects.

Conclusions:

• The novel polyplex-HGC thermogel system is a safe and efficient injectable platform for inner ear gene therapy.
• This system significantly advances gene delivery for treating inner ear disorders like hearing loss and balance impairments.