Initial observations of cell-mediated drug delivery to the deep lung.
Initial observations of cell-mediated drug delivery to the deep lung.
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DOI：
10.3727/096368910x536491
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发表时间：
2011
影响因子：
3.3
通讯作者：
Cameron DF
中科院分区：
文献类型：
--
作者：
Kumar A;Glaum M;El-Badri N;Mohapatra S;Haller E;Park S;Patrick L;Nattkemper L;Vo D;Cameron DF
使用目前的方法，药物递送到小气道、末端细支气管和肺泡（肺深部）是低效的，特别是到下肺。急性呼吸窘迫综合征（ARDS）和肺移植后并发症等紧急肺部病变难以治疗，部分原因是在靶向肺深部并将药物高效分布到病变部位方面存在方法学限制。为了克服抑制肺深部治疗优化的药物递送限制，使用预装载有壳聚糖纳米颗粒的分离的大鼠支持细胞，通过外周静脉血管系统而不是更常用的肺部途径，在小鼠肺中获得纳米颗粒的高密度分布和浓度（92%）。此外，Sertoli细胞预先装载了与抗炎化合物姜黄素偶联的壳聚糖纳米颗粒，然后静脉注射到患有深部肺部炎症的对照或实验小鼠中。注射后24 h，注射的Sertoli细胞中递送的大部分姜黄素负荷（约90%）存在并分布在整个肺中，包括下肺中的肺泡周围囊区。这是基于肺中纳米颗粒和姜黄素的高密度阳性定量。通过该支持细胞纳米颗粒方案（SNAP）提供姜黄素治疗后24小时，取得了显着的积极治疗效果。结果确定了一种新的和有效的协议，有针对性地提供药物的深部肺睾丸支持细胞介导的。利用SNAP递送可以优化用于诸如ARDS、哮喘持续状态、肺动脉高压、肺癌和肺移植后并发症的病症的药物治疗，其中期望使用高浓度的抗炎药物，但通常受到全身药物毒性风险的限制。
Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (~90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.