Development of an inhalable nanomedicine for lung cancer

Abstract

Lung cancer affects over 2 million people worldwide and became the major cause of death in cancer patients (18.4%) in 2018. The treatment of non-small cell lung cancer (NSCLC), accounting for 85% of total lung cancer, involves chemotherapy, radiotherapy, and surgery. However, such a therapeutic option for NSCLC demonstrate limited success in the treatment proved by the poor 5-year survival rate (~15%) that has remained relatively unchanged for the last three decades. Therefore, a new therapeutic option targeting specific genes/proteins has gained traction to obtain a better therapeutic outcome and avoid the undesired adverse effect, one of which is gene therapy. Different nucleic acids have been investigated, combined with gene-vector to form nanoparticle (NP) and penetrate cellular membrane for intracellular action. The NPs can also be formulated into inhalable powder using a spray drying method for pulmonary delivery. However, the main challenge is maintaining the stability and functionality of NPs. Herein, RALA peptide that had been successfully incorporated into different formulations, e.g. wound patch and hydrogel, was used to condense plasmid DNA (pEGFP-N1) into NPs, followed by spray drying to produce inhalable powder as a proof of concept of gene therapy for lung cancer treatment. The functionality of RALA/pEGFP-N1 NPs was evaluated in subcutaneous connective tissue and adenocarcinoma human alveolar epithelial cells. RALA peptide was highly efficient at condensing and delivering pEGFP-N1 into cells and resulted in gene expression in the selected cell lines. Thereafter, inhalable RALA/pEGFP-N1 NPs were produced via spray drying using a nano-spray dryer, resulting in the maintained stability and functionality of RALA/pEGFP-N1 NPs. These findings revealed that spray drying process also generated desired powder characteristics, even at low-temperature drying and without any aerosolisation enhancer. Successful optimisation to produce inhalable powder containing functional NPs was achieved through the design of experiments approach.

Thesis embargoed until 31 July 2027.

Date of Award	Jul 2022
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Indonesia Endowment Fund for Education (Lembaga Pengelola Dana Pendidikan/LPDP)
Supervisor	Vicky Kett (Supervisor) & Helen McCarthy (Supervisor)