title: 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.
authors: Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
authors: Elke
authors: E
authors: Kleemann
authors: Norman
authors: N
authors: Jekel
authors: Lea Ann
authors: LA
authors: Dailey
authors: Susanne
authors: S
authors: Roesler
authors: Ludger
authors: L
authors: Fink
authors: Norbert
authors: N
authors: Weissmann
authors: Ralph
authors: R
authors: Schermuly
authors: Tobias
authors: T
authors: Gessler
authors: Thomas
authors: T
authors: Schmehl
authors: Clive J
authors: CJ
authors: Roberts
authors: Werner
authors: W
authors: Seeger
authors: Thomas
authors: T
authors: Kissel
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D007097:Imines / Q000737:chemistry; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D014162:Transfection / Q000379:methods
chemical_list: D007097:Imines; D011095:Polyethylenes; D011108:Polymers; C505405:poly(ethylene imine); D011092:Polyethylene Glycols; D004247:DNA; D008156:Luciferases