Enhanced gene expression and reduced toxicity in mice using polyplexes of low-molecular-weight poly(ethylene imine) for pulmonary gene delivery

Abstract

The aim of this study was to elicit improved gene expression and decreased cytotoxicity for pulmonary gene therapy by replacing the commonly used carrier 25 kDa branched poly(ethylene imine) (BPEI) by two PEI derivatives, low-molecular-weight PEI (LMWPEI) and polyethylene glycol−grafted PEI (PEGPEI). All polymers were shown to condense DNA to spherical particles of approximately 100 nm. Biocompatibility was investigated in vitro and in vivo. Although transfection was less efficient with LMWPEI-DNA in vitro, this polyplex caused the highest luciferase expression in the mouse lung after intratracheal instillation. While PEGPEI luciferase expression in vitro was approximately three times higher when compared to BPEI, a transfection rate at the level of naked DNA was observed in vivo. LMWPEI polyplexes were located in both the bronchial and alveolar cells, whereas BPEI polyplexes were mainly detected in bronchial cells. LMWPEI combines low cytotoxicity with high transfection efficiency in the mouse lung in vivo, rendering it a promising strategy for pulmonary gene delivery.

Keywords::

• Low-molecular-weight PEI
• pulmonary gene delivery
• transfection efficiency
• intratracheal instillation
• cytotoxicity

Acknowledgments

The authors would like to acknowledge Nicole Bamberger, Eva Mohr, and Christiane Held for their technical assistance. We are also grateful to the DFG graduation college 534 in Giessen and the DFG Forschergruppe 627 for financial support.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and the writing of the paper.