Modeling the gene delivery process of the needle array-based tissue nanotransfection

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Dermatology

Background:

• Tissue nanotransfection (TNT) is an in vivo gene delivery method using electric pulses.
• Understanding TNT's gene delivery mechanisms in skin is crucial for its clinical translation.

Purpose of the Study:

• To simulate and experimentally validate the gene delivery process of hollow needle array-based TNT in skin.
• To investigate the factors influencing electroporation and gene delivery depth.

Main Methods:

• Asymptotic method and cell-array-based modeling for electroporation analysis.
• Multilayer-stack-based modeling for gene delivery simulation.
• Experimental validation of simulation results.

Main Results:

• Nonuniform electric fields across the skin lead to varied cell electroporation.
• Cells under hollow microchannels showed the highest pore numbers due to localized electric fields.
• Increasing voltage from 100 to 150 V/mm increased electroporated cells from 25% to 82%.
• Gene delivery distance increased nonlinearly with voltage and pulse number, influenced by tissue properties.
• Skin exfoliation prior to TNT enhances delivery depth.

Conclusions:

• The study provides a foundational understanding of TNT gene delivery in skin.
• Optimized voltage and skin preparation are key for efficient gene delivery.
• Findings support the translation of TNT from murine models to larger animals and human applications.