Formulation of RNA interference-based Drugs for Pulmonary delivery: Challenges and Opportunities

Abstract

With recent advances in the field of RNAi-based therapeutics, it is possible to make any target gene ‘druggable’, at least in principle. The present review focuses on aspects critical for pulmonary delivery of formulations of nucleic acid-based drugs. The first part introduces the therapeutic potential of RNAi-based drugs for the treatment of lung diseases. Subsequently, we discuss opportunities for formulation-enabled pulmonary delivery of RNAi drugs in light of key physicochemical properties and physiological barriers. In the following section, an overview is included of methodologies for imparting inhalable characteristics to nucleic acid formulations. Finally, we review one of the bottlenecks in the early preclinical testing of inhalable nucleic acid-based formulations, in other words, devices suitable for pulmonary administration of powder-based formulations in rodents.

Keywords:

• aerodynamic properties
• cationic lipids
• dry powder formulations
• lung diseases
• nanoparticles
• nucleic acids
• preclinical testing
• pulmonary delivery
• RNA interference
• spray drying

Financial & competing interests disclosure

The authors gratefully acknowledge financial support from the Lundbeck Foundation–Denmark (grant no. R219-2016-908), the Novo Nordisk Foundation–Denmark (grant no. NNF17OC0026526) and Independent Research Fund Denmark (grant no. DFF-4184-00422). K Thanki and C Foged are coinventors of a patent application relating to a cationic lipid structure (European PCT application number 57590PC01). All rights have been assigned to University of Copenhagen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Author's contributions

K Thanki and C Foged outlined the layout of review paper. K Thanki, KG Blum, A Thakur and F Rose wrote the whole paper. C Foged edited the whole manuscript. All the authors checked the manuscript.