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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents



ID: 474518.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Enhanced gene expression and reduced toxicity in mice using polyplexes of low-molecular-weight poly(ethylene imine) for pulmonary gene delivery
Authors:Kleemann, E.; Jekel, N.; Dailey, L. A.; Roesler, S.; Fink, L.; Weissmann, N.; Schermuly, R.; Gessler, T.; Schmehl, T.; Roberts, C. J.; Seeger, W.; Kissel, T.
Date of Publication (YYYY-MM-DD):2009
Title of Journal:J Drug Target
Volume:17
Issue / Number:8
Start Page:638
End Page:51
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals; Bronchi/cytology/metabolism; DNA/metabolism; *Gene Expression Regulation; Gene Therapy/adverse effects/*methods; *Gene Transfer Techniques/adverse effects; Imines/chemistry; Luciferases/genetics; Lung/*metabolism; Mice; Mice, Inbred C57BL; Molecular Weight; Polyethylene Glycols/chemistry; Polyethylenes/chemistry; Polymers/chemistry; Transfection/methods
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Department of Pharmaceutics and Biopharmacy, Philipps-University, Marburg, Germany.
Identifiers:ISSN:1029-2330 (Electronic) 1026-7158 (Linking)
URL:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=..
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