NDLI: Electrohydrodynamic Comminution: A Novel Technique for the Aerosolisation of Plasmid DNA

Content Provider	Springer Nature Link
Author	Davies, Lee A. Hannavy, Kevin Davies, Neville Pirrie, Alistair Coffee, Ronald A. Hyde, Stephen C. Gill, Deborah R.
Copyright Year	2005
Abstract	Naked plasmid DNA (pDNA) is a potential gene transfer agent for lung gene therapies but cannot be aerosolised without degradation using conventional nebulisation devices. This study investigated the viability of an alternative nebulisation technique, electrohydrodynamic (EHD) comminution for the aerosol delivery of naked DNA in vivo.Naked pDNA was aerosolised using jet and ultrasonic nebulisers, and by EHD comminution. Degradation associated with the aerosolisation process was investigated using gel electrophoresis and by transfection studies in cell culture. Optimised formulations for EHD aerosolisation of pDNA were developed and in vivo deposition and reporter gene expression were investigated in mice.Unlike conventional nebulisation devices, EHD comminution of plasmids up to 15 kb in size resulted in no detectable pDNA degradation. EHD formulations containing up to 1 mg/ml pDNA were developed and shown to produce monodisperse aerosols suitable for targeted lung delivery in humans. Aerosolisation studies in vivo demonstrated detectable levels of pDNA deposition and measurable luciferase reporter gene expression in the lungs of exposed mice.This study demonstrates for the first time that respirable aerosols of naked pDNA can be generated without plasmid degradation and that EHD comminution is an appropriate technique for the aerosolisation of delicate gene transfer agents.
Starting Page	1294
Ending Page	1304
Page Count	11
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	22
Issue Number	8
e-ISSN	1573904X
Language	English
Publisher	Springer-Verlag
Publisher Date	2005-08-03
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	aerosolisation electrohydrodynamic gene transfer naked DNA Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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