Spray drying: Inhalable powders for pulmonary gene therapy

Area of Science:

• Pulmonary drug delivery
• Gene therapy formulation
• Respiratory medicine

Background:

• Gene therapy shows promise for lung pathologies, with increasing clinical trials.
• Pulmonary delivery via inhalation offers localized treatment and enhanced absorption.
• Challenges include nucleic acid degradation, clearance, and deposition during aerosolization.

Purpose of the Study:

• To review ideal characteristics for pulmonary gene therapy delivery using inhalable formulations.
• To evaluate spray drying for producing stable, nucleic acid-containing dry powder inhalers (DPIs).
• To analyze the impact of instrument parameters, delivery systems, and excipients on cargo stability.

Main Methods:

• Review of existing literature on pulmonary gene therapy and dry powder inhaler formulation.
• Evaluation of spray drying techniques for producing inhalable nucleic acid formulations.
• Analysis of factors influencing nucleic acid stability and functionality within DPIs.

Main Results:

• Dry powder inhalers (DPIs) offer advantages over nebulization and pMDIs for stable, dry formulations.
• Spray drying is a viable method for producing nucleic acid-loaded DPIs.
• Excipients, solvent systems, and instrument parameters significantly affect cargo stability and function.

Conclusions:

• Developing stable, inhalable gene therapy formulations is critical for effective pulmonary treatment.
• Spray-dried DPIs represent a promising approach for delivering gene therapies to the lungs.
• Optimization of formulation and processing parameters is key to ensuring nucleic acid integrity and therapeutic efficacy.