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Anticancer Efficacy of Oral Docetaxel Nanoformulation for Metronomic Chemotherapy in Metastatic Lung Cancer.
Journal of Biomedical Nanotechnology Pub Date : 2020-9-14 , DOI: 10.1166/jbn.2020.2925
Sophia Le , Chun-Mien Chang , Tina Nguyen , Yuzhou Liu , Yu-An Chen , Elizabeth Hernandez , Payal Kapur , Jer-Tsong Hsieh , Keith Johnston , Xiaowei Dong

Metronomic chemotherapy, giving low doses of chemotherapeutics (e.g., docetaxel) on a frequent schedule over a long time, may improve outcomes and reduce side effects for cancer patients. Oral medications are vital for applying metronomic chemotherapy. However, low solubility, low absorption, low drug availability in the targeted tissue, and side effects limit the development of oral chemotherapeutics. Many chemotherapeutics are intravenously delivered. In this work, we developed a new docetaxel granule that produces docetaxel-loaded in situ self-assembled nanoparticle (180 nm) upon contact with water. The process of manufacturing docetaxel granules is scalable in industrial settings. The lung selectivity of docetaxel granule was observed in animals. The mechanistic studies demonstrated the nanoparticle bound with red blood cells, which selectively delivers docetaxel to the lungs. Finally, docetaxel granule (5 mg/kg twice per week) can profoundly inhibit the tumor growth of lung-metastatic cancer xenograft model over 24 days. The material-based lungselective oral nanoformulation provides an opportunity for conventionally intravenous chemotherapy drugs to be easily applied in oral administration for metronomic chemotherapy for cancer patients with lung cancers.

中文翻译:

口服多西他赛纳米制剂对转移性肺癌的节律化疗的抗癌作用。

在长时间内频繁地进行低剂量化学疗法(例如多西他赛)的节律化学疗法可改善结果并减少对癌症患者的副作用。口服药物对于应用节律化疗至关重要。但是,低溶解度,低吸收,目标组织中药物的利用率低以及副作用限制了口服化学疗法的发展。许多化学疗法是静脉内递送的。在这项工作中,我们开发了一种新的多西他赛颗粒剂,该颗粒可原位生产多西他赛与水接触后自组装的纳米粒子(180 nm)。多西紫杉醇颗粒的生产工艺在工业环境中可扩展。在动物中观察到多西他赛颗粒的肺选择性。机理研究表明,纳米颗粒与红细胞结合,可选择性地将多西他赛递送至肺部。最后,多西他赛颗粒(每周两次两次5 mg / kg)可以在24天之内深刻抑制肺癌转移性异种移植模型的肿瘤生长。基于材料的肺选择性口服纳米制剂为常规的静脉化疗药物提供了机会,可以轻松地将其用于口服给药,用于肺癌患者的节律化疗。
更新日期:2020-09-16
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