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In Vivo Pulmonary Delivery and Magnetic-Targeting of Dry Powder Nano-in-Microparticles
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00532 Dominique N. Price 1 , Loreen R. Stromberg 1, 2 , Nitesh K. Kunda 1 , Pavan Muttil 1, 3
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00532 Dominique N. Price 1 , Loreen R. Stromberg 1, 2 , Nitesh K. Kunda 1 , Pavan Muttil 1, 3
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This brief communication evaluates the cytotoxicity and targeting capability of a dry powder chemotherapeutic. Nano-in-microparticles (NIMs) are a dry powder drug delivery vehicle containing superparamagnetic iron oxide nanoparticles (SPIONs) and either doxorubicin (w/w solids) or fluorescent nanospheres (w/v during formulation; as a drug surrogate) in a lactose matrix. In vitro cytotoxicity was evaluated in A549 adenocarcinoma cells using MTS and LDH assays to assess viability and toxicity after 48 h of NIMs exposure. In vivo magnetic-field-dependent targeting of inhaled NIMs was evaluated in a healthy mouse model. Mice were endotracheally administered fluorescently labeled NIMs either as a dry powder or a liquid aerosol in the presence of an external magnet placed over the left lung. Quantification of fluorescence and iron showed a significant increase in both fluorescence intensity and iron content to the left magnetized lung. In comparison, we observed decreased targeting of fluorescent nanospheres to the left lung from an aerosolized liquid suspension, due to the dissociation of SPIONs and nanoparticles during pulmonary administration. We conclude that dry powder NIMs maintain the therapeutic cytotoxicity of doxorubicin and can be better targeted to specific regions of the lung in the presence of a magnetic field, compared to a liquid suspension.
中文翻译：
干粉纳米微粒的体内肺部递送和磁性靶向
这种简短的交流评估了干粉化疗剂的细胞毒性和靶向能力。纳米微粒（NIM）是一种干粉药物输送载体，其含有乳糖中的超顺磁性氧化铁纳米颗粒（SPION）和阿霉素（w / w固体）或荧光纳米球（w / v在配制过程中；作为药物替代物）矩阵。使用MTS和LDH测定法评估A549腺癌细胞的体外细胞毒性，以评估NIM暴露48小时后的生存力和毒性。体内在健康的小鼠模型中评估了吸入NIM的磁场依赖性靶向。在放置于左肺上的外部磁铁存在下，对小鼠进行气管内荧光标记的NIM（干粉或液体气雾剂）给药。荧光和铁的定量显示左磁化肺的荧光强度和铁含量均显着增加。相比之下，由于在肺部给药期间SPIONs和纳米颗粒的解离，我们观察到了雾化的液体悬浮液对荧光纳米球向左肺的靶向作用降低。我们得出的结论是，与液体悬浮液相比，干粉NIM可以维持阿霉素的治疗细胞毒性，并且在存在磁场的情况下可以更好地靶向肺的特定区域。
更新日期：2017-11-09
中文翻译：
干粉纳米微粒的体内肺部递送和磁性靶向
这种简短的交流评估了干粉化疗剂的细胞毒性和靶向能力。纳米微粒（NIM）是一种干粉药物输送载体，其含有乳糖中的超顺磁性氧化铁纳米颗粒（SPION）和阿霉素（w / w固体）或荧光纳米球（w / v在配制过程中；作为药物替代物）矩阵。使用MTS和LDH测定法评估A549腺癌细胞的体外细胞毒性，以评估NIM暴露48小时后的生存力和毒性。体内在健康的小鼠模型中评估了吸入NIM的磁场依赖性靶向。在放置于左肺上的外部磁铁存在下，对小鼠进行气管内荧光标记的NIM（干粉或液体气雾剂）给药。荧光和铁的定量显示左磁化肺的荧光强度和铁含量均显着增加。相比之下，由于在肺部给药期间SPIONs和纳米颗粒的解离，我们观察到了雾化的液体悬浮液对荧光纳米球向左肺的靶向作用降低。我们得出的结论是，与液体悬浮液相比，干粉NIM可以维持阿霉素的治疗细胞毒性，并且在存在磁场的情况下可以更好地靶向肺的特定区域。
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