Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization

Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization

Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI–DNA polyplexes, namely branched (bPEI), linear...

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Bibliographic Details
Published in:Journal of controlled release Vol. 100; no. 3; pp. 437 - 450
Main Authors: Kleemann, E., Dailey, L.A., Abdelhady, H.G., Gessler, T., Schmehl, T., Roberts, C.J., Davies, M.C., Seeger, W., Kissel, T.
Format: Journal Article
Language:English
Published: Amsterdam Elsevier B.V 10-12-2004
Elsevier
Subjects:
Aerosols
Atomic force microscopy
Biological and medical sciences
Deoxyribonucleases - chemistry
DNA - genetics
Drug Delivery Systems
Electrophoresis, Agar Gel
Gene Transfer Techniques
General pharmacology
Genetic Therapy - methods
Laser-Doppler Flowmetry
Light
Medical sciences
Microscopy, Atomic Force
Nebulization
Nebulizers and Vaporizers
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethyleneimine - chemistry
Polyethylenimine
Pulmonary Alveoli - cytology
Pulmonary Alveoli - drug effects
Pulmonary gene therapy
Scattering, Radiation
Stability
Ultrasonics
Pulmonary gene therapy
Atomic force microscopy
Polyethylenimine
Nebulization
Stability
Delivery system
Structure stability
Pharmaceutical technology
Lung
Aerosols
Gene therapy
Polyethylene imine
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Summary:Polyelectrolyte complexes between DNA and polyethylenimine (PEI) are promising non-viral delivery systems for pulmonary inhalation gene therapy and thus require sufficient stability during nebulization. The structure and stability of four different PEI–DNA polyplexes, namely branched (bPEI), linear (linPEI), poly(ethylene glycol)-grafted PEI (PEGPEI), biodegradable (bioPEI) PEI with DNA, were investigated. Using atomic force microscopy, the morphology of DNA and polyplexes before and after both air-jet and ultrasonic nebulization was characterized. The influence of nebulization on physico-chemical properties, particle size and zeta potential, was studied. Efficient DNA condensation to spherical particles was achieved with bPEI (90 nm) and PEGPEI (110 nm). By contrast, incomplete DNA condensations, seen as flower structures, were observed with linPEI (110 nm) and bioPEI (105 nm). Air-jet nebulization altered the polyplex structure to a greater extent than ultrasonic nebulization and resulted mainly in smaller and non-spherical particles (30–200 nm). Ultrasonic nebulization did not change the spherical structure or particle size of the polyplexes. In particular, the shape and size of the PEGPEI polyplexes did not change. We conclude that ultrasonic nebulization is a milder aerosolization method for gene delivery systems based on PEI. Additionally, PEGPEI–DNA polyplexes seem to be more stable than their counterparts, which may be advantageous in pulmonary inhalation gene therapy.
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ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2004.09.005