Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment
Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment
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DOI：
10.1007/s13346-018-0526-4
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发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Rahman, Mohd Basyaruddin Abdul
中科院分区：
文献类型：
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作者：
Asmawi, Azren Aida;Salim, Norazlinaliza;Rahman, Mohd Basyaruddin Abdul
多西紫杉醇对肺癌具有非凡的抗癌作用。然而，由于其溶解性差和治疗剂量的高毒性，缺乏最佳的生物利用度，阻碍了这种抗癌药物的临床应用。开发纳米乳剂配方和生物相容性赋形剂用于肺给药是一种潜在的策略，可以改善这种低水溶性药物的生物利用度和生物相容性。在这项工作中，筛选和选择药用上可接受的辅料，在其最小的最佳浓度进行了。采用高能乳化技术制备了纳米乳液配方，并对其进行了理化和气动表征。制备的纳米乳液平均粒径在90 ~ 110nm， -30 ~ -40mV范围内，具有较高的胶体稳定性。系统的pH值、渗透压和粘度满足肺应用的理想要求。该制剂即使在极端环境条件下也表现出缓慢的释药速度和良好的稳定性。透射电镜进一步证实了这一点，在45 +/- 1℃下储存3个月后，观察到纳米范围内均匀的球形液滴，显示出较高的热稳定性。雾化后的DNE4具有理想的雾化特性，可用于肺输送应用，并且发现对人肺癌细胞（A549）比正常细胞（MRC-5）更具选择性。因此，这些特性使该制剂成为多西紫杉醇通过肺给药靶向肺癌的载体系统的潜在候选药物。
Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and -potential in the range of 90 to 110nm and -30 to -40mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 +/- 1 degrees C for 3months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.