Magnetized Aerosols Comprising Superparamagnetic Iron Oxide Nanoparticles Improve Targeted Drug and Gene Delivery to the Lung

被引:41
作者
Hasenpusch, Guenther [1 ]
Geiger, Johannes [1 ]
Wagner, Kai [2 ]
Mykhaylyk, Olga [3 ]
Wiekhorst, Frank [4 ]
Trahms, Lutz [4 ]
Heidsieck, Alexandra [5 ]
Gleich, Bernhard [5 ]
Bergemann, Christian [6 ]
Aneja, Manish K. [1 ]
Rudolph, Carsten [1 ]
机构
[1] Univ Munich, Dept Pediat, D-80337 Munich, Germany
[2] Univ Munich, Inst Pathol, D-80337 Munich, Germany
[3] Tech Univ Munich, Klinikum Rechts Isar, Inst Expt Oncol, D-81675 Munich, Germany
[4] Phys Tech Bundesanstalt, D-10587 Berlin, Germany
[5] Tech Univ Munich, IMETUM, D-84748 Garching, Germany
[6] Chemicell GmbH, D-10823 Berlin, Germany
关键词
aerosol; cancer; gene delivery; lung; magnetic drug targeting; TERM PARTICLE CLEARANCE; CELLS IN-VITRO; MUCOCILIARY; PACLITAXEL; CARCINOMA; HEALTHY; AIRWAYS; AGENTS;
D O I
10.1007/s11095-012-0682-z
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Targeted delivery of aerosols could not only improve efficacy of inhaled drugs but also reduce side effects resulting from their accumulation in healthy tissue. Here we investigated the impact of magnetized aerosols on model drug accumulation and transgene expression in magnetically targeted lung regions of unanesthetized mice. Solutions containing superparamagnetic iron oxide nanoparticles (SPIONs) and model drugs (fluorescein or complexed plasmid DNA) were nebulized to unanesthetized mice under the influence of an external magnetic gradient directed to the lungs. Drug accumulation and transgene expression was subsequently measured at different time points. We could demonstrate 2-3 fold higher accumulation of the model drug fluorescein and specific transgene expression in lung regions of mice which had been exposed to an external magnetic gradient during nebulization compared to the control mice without any exposure to magnetic gradient. Magnetized aerosols present themselves as an efficient approach for targeted pulmonary delivery of drugs and gene therapeutic agents in order to treat localized diseases of the deeper airways.
引用
收藏
页码:1308 / 1318
页数:11
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