title: Inhaled gene delivery: a formulation and delivery approach.
abstract: Gene therapy is a potential alternative to treat a number of diseases. Different hurdles are associated with aerosol gene delivery due to the susceptibility of plasmid DNA (pDNA) structure to be degraded during the aerosolization process. Different strategies have been investigated in order to protect and efficiently deliver pDNA to the lungs using non-viral vectors. To date, no successful therapy involving non-viral vectors has been marketed, highlighting the need for further investigation in this field. Areas covered: This review is focused on the formulation and delivery of DNA to the lungs, using non-viral vectors. Aerosol gene formulations are divided according to the current delivery systems for the lung: nebulizers, dry powder inhalers and pressurized metered dose inhalers; highlighting its benefits, challenges and potential application. Expert opinion: Successful aerosol delivery is achieved when the supercoiled DNA structure is protected during aerosolization. A formulation strategy or compounds that can protect, stabilize and efficiently transfect DNA into the cells is desired in order to produce an effective, low-cost and safe formulation. Nebulizers and dry powder inhalers are the most promising approaches to be used for aerosol delivery, due to the lower shear forces involved. In this context it is also important to highlight the importance of considering the 'pDNA-formulation-device system' as an integral part of the formulation development for a successful nucleic acid delivery.
authors.affiliation: a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School , Sydney University , Glebe , Australia.
authors.forename: Larissa
authors.initials: L
authors.lastname: Gomes Dos Reis
authors.affiliation: a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School , Sydney University , Glebe , Australia.
authors.forename: Maree
authors.initials: M
authors.lastname: Svolos
authors.affiliation: b Evonik Industries, Nutrition and Care AG , Darmstadt , Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hartwig
authors.affiliation: b Evonik Industries, Nutrition and Care AG , Darmstadt , Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Windhab
authors.affiliation: a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School , Sydney University , Glebe , Australia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.affiliation: a Respiratory Technology, Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School , Sydney University , Glebe , Australia.
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D058995:Dry Powder Inhalers; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008168:Lung / Q000378:metabolism*; D036501:Metered Dose Inhalers; D009330:Nebulizers and Vaporizers; D010957:Plasmids / Q000008:administration & dosage
chemical_list: D000336:Aerosols
keywords: DNA; Non-viral; dry powder inhaler (DPI); nebulizer; pressurized metered dose inhaler (pMDI)