Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, 6th of October City, 12578, Giza, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Eur J Pharm Sci. 2022 Apr 1;171:106119. doi: 10.1016/j.ejps.2022.106119. Epub 2022 Jan 6.
Lung cancer is characterized by poor prognosis, and is considered a serious disease that causes a significant mortality. The available conventional chemotherapeutic agents suffer from several limitations; hence, new drug molecules are constantly being sought. In the current study, lipid nanovesicles (LNVs) were selected as a colloidal vehicle for encapsulation of the FDA-approved drug; rolapitant (RP), which is used particularly for the treatment of nausea and vomiting, but is repurposed for the treatment of lung cancer in the current work. RP was loaded into various LNVs (liposomes, ethosomes and transethosomes) using the thin film hydration method, and the LNVs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), storage stability and surface morphology. Besides, the in-vitro drug release, in-vitro cytotoxicity on A549 lung cancer cells, nebulization performance using next generation impactor (NGI), and the in-vivo biodistribution behavior were evaluated. The selected ethosomal and transethosomal vesicles displayed a particle size less than 400 nm, a positive charge, and EE% exceeding 90% for RP, with a sustained release pattern over 15 days. The in-vivo biodistribution results proved the high lung deposition potential of RP-LNVs with a considerable safety. Besides, the developed RP-LNVs were able to reach the metastatic organs of lung cancer, hence they were proven promising as a possible treatment modality for lung cancer.
肺癌的预后较差，被认为是一种严重的疾病，导致较高的死亡率。现有的常规化疗药物存在多种局限性；因此，人们一直在不断寻找新的药物分子。在本研究中，选择脂质纳米囊（LNV）作为胶束载体来包封已获 FDA 批准的药物；拉洛匹坦（RP），主要用于治疗恶心和呕吐，但在当前工作中被重新用于治疗肺癌。RP 采用薄膜水化法载入各种 LNV（脂质体、醇质体和转醇质体）中，并对 LNV 的粒径、Zeta 电位、包封效率（EE%）、储存稳定性和表面形态进行了评估。此外，还评估了体外药物释放、对 A549 肺癌细胞的体外细胞毒性、下一代撞击器（NGI）的雾化性能以及体内生物分布行为。所选的醇质体和转醇质体囊泡的粒径小于 400nm，带正电荷，RP 的 EE%超过 90%，具有超过 15 天的持续释放模式。体内生物分布结果证明了 RP-LNVs 具有较高的肺部沉积潜力，且安全性良好。此外，所开发的 RP-LNVs 能够到达肺癌的转移器官，因此它们有望成为治疗肺癌的一种可行方法。
