Suyash M. Patil1, Shruti S. Sawant1 & Nitesh K. Kunda1
1 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Jamaica, NY 11439, USA
Summary
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths globally. The available treatment options are limited by adverse effects and development of drug resistance. Hence, newer drug candidates and drug delivery systems that have minimal adverse effects with significant anticancer efficacy are required. For NSCLC treatment, inhalation route of drug delivery is highly beneficial as it delivers drugs directly into the lungs, requires lower doses, and limits systemic toxicity. Bedaquiline (BQ), an anti-tuberculosis drug has previously shown excellent anti-cancer efficacy, but the drug’s poor aqueous solubility limits its delivery via the lungs. In this project, we developed inhalable BQ-loaded cubosome (BQLC) nanocarriers for NSCLC treatment. The BQLC were prepared using a solvent evaporation technique and displayed a particle size of 150.2 ± 5.1 nm, zeta potential of (+) 35.4 ± 2.3 mV, and encapsulation efficiency of 51.85 ± 4.83%. The solid-state characterization (DSC and PXRD) confirmed drug encapsulation within the cubosomes. The BQLC nanocarriers showed excellent aerodynamic properties after nebulization (MMAD of 4.21 ± 0.53 μm and FPF > 75%). The BQLC displayed enhanced cytotoxicity with a ~3-fold reduction in IC50 compared to free BQ in NSCLC (A549) cells, after 48 h treatment. Additionally, 3D-tumor simulation studies established the anticancer efficacy of cubosomal nanocarriers as compared to free BQ.
Key Message
This is the first study exploring the potential of cubosomes for inhaled therapy. Further, the results suggest that bedaquiline-loaded cubosomes could be a promising NSCLC treatment with optimum particle characteristics, excellent aerosolization performance, and enhanced anti-cancer activity.