Methodological optimization of polyethylenimine (PEI)-based gene delivery to the lungs of mice via aerosol application

Carsten Rudolph, A. Ortiz, U. Schillinger, J. Jauernig, C. Plank, J. Rosenecker

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Background. Polyethylenimine (PEI) has been successfully used for gene delivery to the lungs of mice via aerosol application using a whole body nebulization device. In this report we optimized the design of such an aerosol device. Methods. Aerosol devices were constructed as either serial inhalation apparatus or as a whole body nebulization chamber connected to an aerosol spacer placed in a horizontal or vertical position. PEI-based gene vectors were nebulized using a standard jet nebulizer and luciferase gene expression of various tissues was examined. Results. Using a whole body aerosol device resulted in luciferase gene expression in the lungs of mice at the same level as compared with a serial inhalation apparatus. Whereas gene expression was enhanced in the presence of 5% CO2-in-air, anesthesia of mice strongly decreased gene expression even when mice were intubated with an intravascular cannula. Reduction of the median mass aerodynamic diameter (MMAD) of the aerosol from 3.4 to 0.27 μm by interposition of an aerosol spacer increased gene expression significantly 3-fold. Drying of the aerosol by silica gel additionally increased gene delivery significantly 3-fold. Reporter gene expression mediated by branched PEI 25 kDa was 9- and 15-fold higher as compared with linear PEIs of 22 and 25 kDa, respectively, and was dependent on the DNA concentration. Gene expression was detectable as soon as 6 h after gene vector application and reached a maximum after 72 h but was still detectable after 14 days. The presence of Zn2+ did not increase gene expression. Conclusion. We propose aerosol drying as a novel and simple method of optimizing PEI-based gene delivery to the lungs.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
JournalJournal of Gene Medicine
Volume7
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Aerosol
  • Gene therapy
  • Gene transfer
  • Nonviral
  • PEI

Fingerprint

Dive into the research topics of 'Methodological optimization of polyethylenimine (PEI)-based gene delivery to the lungs of mice via aerosol application'. Together they form a unique fingerprint.

Cite this