Inhaled gene delivery: a formulation and delivery approach

Area of Science:

• Pulmonary Drug Delivery
• Gene Therapy
• Nanotechnology

Background:

• Gene therapy offers a promising treatment for various diseases, but aerosol delivery faces challenges due to plasmid DNA (pDNA) degradation.
• Current non-viral vector strategies for lung gene delivery require further development, as no such therapies are yet marketed.

Purpose of the Study:

• To review formulation and delivery strategies for aerosol gene therapy to the lungs using non-viral vectors.
• To analyze the benefits, challenges, and applications of different delivery systems, including nebulizers, dry powder inhalers, and pressurized metered dose inhalers.

Main Methods:

• Literature review of aerosol gene delivery systems and formulation strategies.
• Analysis of pDNA protection mechanisms during aerosolization.
• Evaluation of different inhalation devices for gene delivery to the lungs.

Main Results:

• Successful aerosol gene delivery hinges on protecting the supercoiled pDNA structure during aerosolization.
• Nebulizers and dry powder inhalers show promise due to lower shear forces, minimizing pDNA degradation.
• A comprehensive 'pDNA-formulation-device system' approach is essential for successful nucleic acid delivery.

Conclusions:

• Developing effective, low-cost, and safe gene therapy formulations requires strategies that protect, stabilize, and facilitate cellular transfection of pDNA.
• Nebulizers and dry powder inhalers are favored for aerosol gene delivery due to their suitability for protecting pDNA.
• Integrated formulation development considering the pDNA, formulation, and delivery device is key to advancing aerosol gene therapy.