Dry powder aerosols of polyethylenimine (PEI)-based gene vectors mediate efficient gene delivery to the lung

• Published in: Journal of controlled release Vol. 154; no. 1; pp. 69 - 76
• Main Authors: Pfeifer, Corinna, Hasenpusch, Guenther, Uezguen, Senta, Aneja, Manish Kumar, Reinhardt, Dietrich, Kirch, Julian, Schneider, Marc, Claus, Sarah, Frieß, Wolfgang, Rudolph, Carsten
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 25.08.2011; Elsevier
• Subjects: Aerosols; Animals; Biological and medical sciences; Blood; Cakes; Cell Line; Controlled release; Crystallization; DNA; Drug Carriers - chemistry; Drug Compounding; Dry powder aerosol; Erythropoietin; Erythropoietin - administration & dosage; Erythropoietin - genetics; Expression vectors; Female; Freeze Drying; Gene delivery; gene expression; Gene transfer; Gene Transfer Techniques; General pharmacology; genes; Genes, Reporter; genetic vectors; Hematocrit; In vivo; Lactose; Luciferases - genetics; Lung; Lung - metabolism; Lung diseases; lungs; Medical sciences; Mice; Mice, Inbred BALB C; Microscopy, Scanning Probe; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasmids; Plasmids - administration & dosage; Plasmids - genetics; Polyethyleneimine - chemistry; Polyethylenimine (PEI); Powder; Powders; respiratory tract diseases; screening; Sucrose; Sugar; Surface Properties; Transfection; Trehalose; Polyethylenimine (PEI); Gene delivery; In vivo; Dry powder aerosol; Lung; Pharmaceutical technology; Powder; Genetic transfer; Polyelectrolyte; Gene; Aerosols; Genetics; Olefinimine polymer; Gene therapy; Vector; Polyethylene imine
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.05.006

Aerosol gene delivery holds great therapeutical potential for many inherited and acquired pulmonary diseases. The physical instability of aqueous suspensions of non-viral vector complexes is a major limitation for their successful application. In this study, we investigated dry powder aerosols as novel gene vector formulations for gene transfer in vitro and murine lungs in vivo. Lyophilization was used to produce dry powder cakes followed by powderization to produce dry powder aerosols. Different sugars, namely lactose, sucrose and trehalose, were tested as lyoprotectants for gene delivery complexes consisting of branched polyethylenimine 25 kDa and plasmid DNA. Biophysical particle characterization demonstrated that lyophilization and powderization in the presence of lyoprotectants were well tolerated. In vitro transfection efficiency remained unaffected by the choice of lyoprotectant and subsequent lyophilization and/or powderization. In vivo screening of powderized samples, by applying the powder with an insufflator, resulted in highest gene expression with lactose as lyoprotectant. Delivering a plasmid coding for murine erythropoietin together with lactose as lyoprotectant resulted in increased blood hematocrit values post application thereby demonstrating the potential of dry powder aerosol as a promising method for pulmonary gene delivery. [Display omitted]