Biochemistry Department, Ege University Faculty of Science, Izmir, Turkey; Ege University Center for Drug Research, Development and Pharmacokinetic Applications, Izmir, Turkey.
Biochemistry Department, Ege University Faculty of Science, Izmir, Turkey; Ege University Center for Drug Research, Development and Pharmacokinetic Applications, Izmir, Turkey.
J Pharm Sci. 2019 Mar;108(3):1272-1283. doi: 10.1016/j.xphs.2018.10.030. Epub 2018 Oct 26.
Non-small cell lung cancer (NSCLC) constitutes more than 85% of lung cancer case. Pemetrexed is used to treat types of NSCLC, and pazopanib is used for some types of soft tissue sarcoma. The aim of the study was development of pemetrexed and pazopanib carrying nanobubble system with magnetic responsiveness and ultrasound sensitivity properties for targeted NSCLC therapy. Drugs were linked to newly designed peptide, and peptide drug conjugates were attached to amine-modified magnetite. Resulting nanoparticles were encapsulated into liposomes, and liposomes were extruded, then nanobubble system was prepared. Moreover, nanobubble biodistribution was monitored by in vivo imaging system. As a result, based on high-performance liquid chromatography data, magnetite and peptide-pemetrexed were conjugated with 54.02% yield, and magnetite and peptide-pazopanib were bound with 63.53% yield. Hydrodynamic size of nanobubbles, prepared from liposomes filtered through 800 nm and 400 nm, was determined as 491.1 ± 130.2 and 275.8 ± 117.8 nm, respectively. Carrier system was accumulated into tumor area with 80.22% yield of the injected carrier system. It was found that nanobubbles were magnetic responsive for accumulation via magnetic field and could be disrupted by ultrasound via focused acoustic pressure, which lead to targeted drug delivery. These nanobubble systems could be investigated for intravenous and inhaler administration in further studies.
非小细胞肺癌（NSCLC）占肺癌病例的 85%以上。培美曲塞用于治疗某些类型的非小细胞肺癌，帕唑帕尼用于治疗某些类型的软组织肉瘤。本研究的目的是开发具有磁响应性和超声敏感性的培美曲塞和帕唑帕尼纳米气泡系统，用于靶向治疗非小细胞肺癌。将药物与新设计的肽连接，将肽药物偶联物连接到胺修饰的磁铁矿上。得到的纳米颗粒被包封在脂质体中，然后将脂质体挤出，制备纳米气泡系统。此外，通过体内成像系统监测纳米气泡的生物分布。结果，根据高效液相色谱数据，磁铁矿和肽培美曲塞的偶联产率为 54.02%，磁铁矿和肽帕唑帕尼的偶联产率为 63.53%。通过 800nm 和 400nm 过滤的脂质体制备的纳米气泡的水动力学直径分别为 491.1±130.2nm 和 275.8±117.8nm。载体系统的肿瘤区累积率为注入载体系统的 80.22%。结果发现，纳米气泡具有通过磁场进行磁响应聚集的能力，并且可以通过聚焦声压破坏超声，从而实现靶向药物递送。这些纳米气泡系统可在进一步的研究中进行静脉内和吸入给药的研究。
