Zhang Tongtong, Wang Rui, Li Miao, Bao Jianwei, Chen Yanming, Ge Yuanyuan, Jin Yiguang
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Anhui Medical University, Hefei 230001, China; Shenyang Pharmaceutical University, Shenyang 110016, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China; Shenyang Pharmaceutical University, Shenyang 110016, China.
Eur J Pharm Sci. 2020 Apr 18;149:105352. doi: 10.1016/j.ejps.2020.105352.
Oral gefitinib tablets are widely applied for the treatment of non-small cell lung cancer (NSCLC) though its broad distribution in the body may result in weak therapeutic efficiency and undesired side effects. Here, liposomal gefitinib dry powder inhalers (LGDs) were prepared using the injection-lyophilization method. LGDs were rough porous particles under a scanning electron microscope, which can be rapidly rehydrated to liposomes. LGDs and gefitinib powders were separately intratracheally (i.t.) administered into the lungs of primary lung cancer rats, while powdered gefitinib tablets were orally administered. Gefitinib was rapidly absorbed from the lung after i.t. administration of LGDs. The maximal gefitinib concentration in the circulation and the area under curve (AUC) of i.t. LGDs were higher than those of i.t. gefitinib powders and oral gefitinib. More importantly, much higher concentration and longer retention of gefitinib in the lung were shown after i.t. administration of LGDs and gefitinib powders but remarkably less drug distribution in the liver compared to oral gefitinib. LGDs showed higher therapeutic effect on rat primary lung cancer than i.t. gefitinib powders and oral gefitinib with reduction of inflammation, weak lung injury, and high apoptosis. Combination of inhalation and liposomes of anticancer drugs is a promising strategy for treatment of primary lung cancer.
口服吉非替尼片广泛应用于非小细胞肺癌（NSCLC）的治疗，但其在体内广泛分布可能导致治疗效果不佳和出现不良副作用。在此，采用注射冻干法制备了脂质体吉非替尼干粉吸入剂（LGDs）。在扫描电子显微镜下，LGDs为粗糙多孔颗粒，可迅速复水形成脂质体。将LGDs和吉非替尼粉末分别经气管内（i.t.）给药至原发性肺癌大鼠肺部，而将吉非替尼片粉末口服给药。经气管内给予LGDs后，吉非替尼迅速从肺部吸收。经气管内给予LGDs后，循环中吉非替尼的最大浓度和曲线下面积（AUC）高于经气管内给予吉非替尼粉末和口服吉非替尼。更重要的是，经气管内给予LGDs和吉非替尼粉末后，肺部吉非替尼的浓度更高且滞留时间更长，但与口服吉非替尼相比，肝脏中的药物分布明显更少。与经气管内给予吉非替尼粉末和口服吉非替尼相比，LGDs对大鼠原发性肺癌显示出更高的治疗效果，具有减轻炎症、减轻肺损伤和高凋亡率的作用。吸入与抗癌药物脂质体相结合是治疗原发性肺癌的一种有前景的策略。
