Ho Wan Chan1, Jinghan Yu2, Xinyue Zhang1, Hoi Hin Kwok3, David Chi Leung Lam3 & Shing Fung Chow1,2
1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R., China
2Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, Hong Kong S.A.R, China
3Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong S.A.R, China
Summary
Combining nanotechnology and inhaled drug delivery could potentially improve therapeutic outcomes for lung cancer treatment. This study aimed to evaluate the efficacy of an inhalable paclitaxel nanoagglomerate dry powder formulation (PTX-NADP) in biorelevant preclinical models of lung cancer. Aerosolised PTX-NADP demonstrated a dose-dependent response in an in vitro air-liquid interface (ALI) lung cancer organoid (LCO) model, which can mimic inhaled aerosol deposition and the lung cancer microenvironment. Intravenous (IV) and intratracheal (IT) instillation of nanosuspensions reconstituted from PTX-NADP demonstrated similar tumour growth suppression in an A549 orthotopic lung cancer mouse model, with their combination seemingly achieving greater suppression. Overall, the study results demonstrate the capability of the ALI LCO model to inform dose selection of inhaled chemotherapeutics and the therapeutic potential of inhaled PTX-NADP chemotherapy in biorelevant preclinical models of lung cancer, and also support further investigating the therapeutic intensification strategy of combining systemic with inhaled chemotherapy to maximise therapeutic response in lung cancer treatment.