Design and evaluation of folate-modified liposomes for pulmonary administration in lung cancer therapy

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.