bedaquiline and Carcinoma--Non-Small-Cell-Lung

Topics: A549 Cells; Administration, Inhalation; Antibiotics, Antineoplastic; Antitubercular Agents; beta-Cyclodextrins; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Diarylquinolines; Drug Carriers; Drug Repositioning; Humans; Lung Neoplasms; Models, Molecular

Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths globally. Treatment-related adverse effects and development of drug resistance limit the available treatment options for most patients. Therefore, newer drug candidates and drug delivery systems that have limited adverse effects with significant anti-cancer efficacy are needed. For NSCLC treatment, delivering drugs via inhalation is highly beneficial as it requires lower doses and limits systemic toxicity. Bedaquiline (BQ), an FDA-approved anti-tuberculosis drug has previously shown excellent anti-cancer efficacy. However, poor aqueous solubility limits its delivery via the lungs. In this project, we developed inhalable BQ-loaded cubosome (BQLC) nanocarriers against NSCLC. The BQLC were prepared using a solvent evaporation technique with the cubosomal nanocarriers exhibiting 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 XRD) confirmed drug encapsulation and in an amorphous form 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 cellular internalization and cytotoxicity with a ~ 3-fold reduction in IC

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Diarylquinolines; Humans; Lung Neoplasms; Nanoparticles; Particle Size