Kaga Elif, Kaga Sadik, Altunbas Korhan, Okumus Nurullah
Department of Medical Services and Techniques, Afyonkarahisar Health Sciences University, Afyonkarahisar, 03030, Türkiye.
Department of Biomedical Engineering, Afyon Kocatepe University, Afyonkarahisar, 03200, Türkiye.
Macromol Biosci. 2025 May;25(5):e2400567. doi: 10.1002/mabi.202400567. Epub 2025 Jan 30.
Chemotherapy is generally given by intravenous (IV) administration which provides higher bioavailability than other systemic routes. However, in the case of lung cancer, the pulmonary (INH) route is the other choice for inhalable formulations. In the study, biochemical and histological parameters of Cabazitaxel (CBZ) free (2 mg kg) and nanoparticle (NP) (2 mg kg CBZ equivalent) formulations are investigated after IV and INH administration in rats. The nanoformulation of CBZ is obtained using PEGylated polystyrene (PEG-PST) nanoparticles obtained by PISA. While a nose and head-only device is used for INH administration, a jugular vein is used as the IV route. Blood samples (blank, 24 h, and 48 h) are collected via carotid artery cannulas without handling in metabolism cages. According to biochemical parameters, free CBZ formulation applied via IV or INH route shows higher systemic toxicity. On the other hand, the nanoformulation of CBZ showed no signs of toxicity in both IV or INH routes. Higher and longer retention is observed in the case of inhaled nanoformulation. Histological analysis showed higher alveolar macrophage migration for inhaled nanoformulation due to enhanced retention. Results showed that nanotechnology and the lung defense system gave the advantage to end up with an inhalable nanomedicine formulation for lung cancer.
化疗通常通过静脉注射给药,其生物利用度高于其他全身给药途径。然而,对于肺癌,肺部(吸入)途径是可吸入制剂的另一种选择。在该研究中,在大鼠静脉注射和肺部吸入给药后,对卡巴他赛(CBZ)游离制剂(2mg/kg)和纳米颗粒制剂(相当于2mg/kg CBZ)的生化和组织学参数进行了研究。CBZ纳米制剂是使用通过引发剂连续自组装(PISA)获得的聚乙二醇化聚苯乙烯(PEG-PST)纳米颗粒制备的。肺部吸入给药使用仅针对鼻和头部的装置,而静脉注射途径则使用颈静脉。通过颈动脉插管采集血样(空白、24小时和48小时),且不将大鼠置于代谢笼中处理。根据生化参数,通过静脉注射或肺部吸入途径应用的游离CBZ制剂显示出更高的全身毒性。另一方面,CBZ纳米制剂在静脉注射或肺部吸入途径中均未显示出毒性迹象。吸入纳米制剂的药物保留更高且持续时间更长。组织学分析表明,由于药物保留增强,吸入纳米制剂的肺泡巨噬细胞迁移更高。结果表明,纳米技术和肺部防御系统有助于最终获得用于肺癌的可吸入纳米药物制剂。