Innovative Applications of Excipients in Gene Therapy Drug Delivery Systems

Gene therapy is transforming medicine, but safe and efficient delivery remains a key challenge. Beyond traditional vectors like viral carriers and lipid nanoparticles, pharmaceutical excipients are emerging as vital components that enhance gene delivery systems.

Importance of Excipients in Gene Therapy

Excipients traditionally modify drug properties for stability and patient use. In gene therapy, they:

• Protect DNA/RNA from degradation

• Aid cell membrane penetration

• Improve formulation stability

• Facilitate endosomal escape

• Enhance tissue-specific targeting

• Reduce immunogenicity and toxicity

These functions are crucial for non-viral gene delivery platforms relying heavily on formulation design.

Key Excipients Applications

1. Stabilization of Genetic Material
   Excipients like trehalose, sucrose, and polyols protect fragile mRNA, siRNA, and plasmid DNA during storage and lyophilization.

2. Endosomal Escape
   pH-sensitive polymers (e.g., polyethyleneimine, Eudragit®) and surfactants help genetic cargo exit endosomes into the cytoplasm.

3. Targeting and Biodistribution
   PEGylated excipients and ligand-modified polymers (e.g., mannose-conjugated) improve delivery to specific cells like macrophages or dendritic cells.

4. Immune Modulation
   Cholesterol derivatives and zwitterionic polymers reduce immune detection and prolong nanoparticle circulation.

5. Bioadhesion and Mucoadhesion
   In mucosal delivery (nasal/oral), excipients like chitosan, carbomers, and hyaluronic acid enhance adhesion and gene transfer efficiency.

Emerging Trends

• Stimuli-responsive excipients (pH, temperature, enzymes) for precision delivery

• Use of biodegradable polymers (PLA, PLGA) for controlled release

• Dual-function excipients that stabilize and enhance transfection efficiency

Regulatory Outlook

With excipients playing active roles, regulatory bodies (FDA, EMA) require thorough safety and functional evaluations, including toxicity and pharmacokinetic data, especially for novel excipients in gene therapies.

Conclusion

Pharmaceutical excipients are now critical to advancing gene therapy delivery. Their innovative use overcomes key barriers to safe, targeted, and effective gene transfer. As gene therapies move toward commercialization, excipient development will be essential to personalized medicine’s future.