Role of biophysical parameters on ex vivo and in vivo gene transfer to the airway epithelium by polyethylenimine/albumin complexes

Sante Di Gioia, Joanna Rejman, Salvatore Carrabino, Ida De Fino, Carsten Rudolph, Ann Doherty, Laura Hyndman, Maurizio Di Cicco, Elena Copreni, Alessandra Bragonzi, Carla Colombo, A. Christopher Boyd, Massimo Conese

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Abstract

Efficient gene transfer to the airways by nonviral vectors is a function of different parameters, among which the size and the charge of the transfecting particles. The aim of this study was to determine the transfection efficiency of polyethylenimine (PEI)/albumin polyplexes in ex vivo and in vivo models of respiratory epithelium and to correlate it with biophysical chqracteristics of the particles. Complexes were obtained by adding different amounts of human serum albumin (HSA) to PEI polyplexes preformed in saline. The presence of HSA caused the formation of bigger and more negative polyplexes and increased PEI transfection efficiency in primary respiratory epithelial cells by 4-6-fold. For in vivo administration to the lung, PEI polyplexes were formed in water and optimized with respect to the N/P ratio.: PEI/pC-Luc complexes gave the highest luciferase expression at N/P 15 when administered through the trachea. At this N/P ratio, the size and the surface charge of albumin-containing polyplexes were not different as compared with plain PEI polyplexes. Formulation of PEI polyplexes in the presence of HSA or murine serum albumin (MSA) resulted in a 2-fold increase in luciferase expression. In mice treated with PEI or PEI/MSA polyplexes containing the nuclear β-gal gene, X-gal staining revealed that transfected cells localized at the bronchiolar epithelium and that PEI/MSA transfected four times as many cells as PEI p <0.05). Finally, double administration! of PEI/MSA polyplexes resulted in a further enhancement of transfection of the lung. Our data show that serum albumin enhances PEI-mediated gene transfer to airway epithelial cells in vivo, likely facilitating the uptake of polyplexes, and indicate that this formulation would fulfill the requirement of repeated administration, as necessary in chronic lung diseases like cystic fibrosis.

Original languageEnglish
Pages (from-to)859-866
Number of pages8
JournalBiomacromolecules
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 2008

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ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Polymers and Plastics
  • Materials Chemistry

Cite this

Di Gioia, S., Rejman, J., Carrabino, S., De Fino, I., Rudolph, C., Doherty, A., Hyndman, L., Di Cicco, M., Copreni, E., Bragonzi, A., Colombo, C., Boyd, A. C., & Conese, M. (2008). Role of biophysical parameters on ex vivo and in vivo gene transfer to the airway epithelium by polyethylenimine/albumin complexes. Biomacromolecules, 9(3), 859-866. https://doi.org/10.1021/bm701190p