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

被引：17

作者：

Kleemann, Elke ^{[1
,2
]}

Jekel, Norman ^{[2
]}

Dailey, Lea Ann ^{[1
]}

Roesler, Susanne ^{[1
,2
]}

Fink, Ludger ^{[2
]}

Weissmann, Norbert ^{[2
]}

Schermuly, Ralph ^{[2
]}

Gessler, Tobias ^{[2
]}

Schmehl, Thomas ^{[2
]}

Roberts, Clive J. ^{[3
]}

Seeger, Werner ^{[2
]}

Kissel, Thomas ^{[1
]}

机构：

[1] Univ Marburg, Dept Pharmaceut & Biopharm, D-35037 Marburg, Germany

[2] UGLC, Giessen, Germany

[3] Univ Nottingham, Sch Pharm, Lab Biophys & Surface Anal, Nottingham NG7 2RD, England

来源：

JOURNAL OF DRUG TARGETING | 2009年 / 17卷 / 08期

关键词：

Low-molecular-weight PEI; pulmonary gene delivery; transfection efficiency; intratracheal instillation; cytotoxicity; DNA/TRANSFERRIN-PEI COMPLEXES; DNA DELIVERY; IN-VITRO; MODIFIED POLYETHYLENIMINES; BRANCHED POLYETHYLENIMINE; TRANSFECTION EFFICIENCY; TRANSGENE EXPRESSION; NONVIRAL VECTOR; MOUSE LUNG; THERAPY;

D O I：

10.1080/10611860903106414

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：638 / 651

页数：14

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