Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan; Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, Japan.
Eur J Pharm Sci. 2022 Jan 1;168:106081. doi: 10.1016/j.ejps.2021.106081. Epub 2021 Nov 21.
Pulmonary drug administration for the treatment of lung cancer is useful because the drug is directly delivered to the lung tissues with minimal invasiveness and higher efficiency compared to other conventional methods. However, it is critical to enhance drug accumulation in the lung cancer tissues to achieve sufficient therapeutic efficacy. The submicron-sized liposome (ssLip) preparation is one of the most promising approaches to enhance drug accumulation in the lungs; however, ssLips prepared for conventional inhalation do not have tumour selectivity. Therefore, in this study, we prepared folate (FA)-modified ssLip (FA-ssLip) to enhance drug accumulation in folate receptor (FR)-expressing lung cancer cells, and evaluated its physicochemical properties and potential as a drug carrier in pulmonary administration. In addition, we prepared rapamycin (RM-an autophagy-inducing anticancer drug)-loaded FA-ssLip (RM/FA-ssLip) and investigated its anti-tumour effect. FA-ssLip showed excellent nanoparticle properties with submicron size (approximately 120 nm) and high lung accumulation in lung cancer mouse model-bearing LL2 cells-a mouse Lewis lung carcinoma cell line. RM/FA-ssLip showed significant cytotoxic activity in FR-expressing cancer cells. In addition, pulmonary administration of RM/FA-ssLip extended the survival of LL2 cell tumour-bearing mice. Taken together, our results suggest the potential of FA-ssLip as a pulmonary drug carrier for the efficient treatment of lung cancer.
肺部给药治疗肺癌具有优势，因为与其他常规方法相比，该方法对肺部组织的侵入性更小，效率更高。然而，提高肺癌组织中药物的蓄积量以达到足够的治疗效果至关重要。亚微米脂质体（ssLip）制剂是提高肺部药物蓄积量的最有前途的方法之一；然而，用于常规吸入的 ssLip 没有肿瘤选择性。因此，在本研究中，我们制备了叶酸（FA）修饰的 ssLip（FA-ssLip）以增强叶酸受体（FR）表达的肺癌细胞中药物的蓄积量，并评估了其作为肺部给药载体的理化性质和潜力。此外，我们还制备了载雷帕霉素（RM-一种诱导自噬的抗癌药物）的 FA-ssLip（RM/FA-ssLip），并研究了其抗肿瘤作用。FA-ssLip 表现出优异的纳米颗粒特性，具有亚微米大小（约 120nm），并且在携带 LL2 细胞（一种小鼠 Lewis 肺癌细胞系）的肺癌小鼠模型中具有较高的肺部蓄积量。RM/FA-ssLip 在表达 FR 的癌细胞中表现出显著的细胞毒性活性。此外，RM/FA-ssLip 的肺部给药延长了携带 LL2 细胞肿瘤的小鼠的存活期。综上所述，我们的研究结果表明 FA-ssLip 作为肺部药物载体具有治疗肺癌的潜力。
