可吸入bedaquiline -loaded cubosomes for the treatment of non-small cell lung cancer (NSCLC)

Highlights

•Bedaquiline-loaded cubosomes (BQLC) displayed excellent particle size,Zeta潜力, and aerosolization behavior suitable forNSCLCtreatment.

•BQLCs were efficiently internalized by lung cancer cells and decreased IC ₅₀ 与游离的bedaquiline相比，三倍。

•BQLC显着抑制了菌落形成和癌症转移 体外。

•在A549 3D球体中，与游离BQ相比，BQLC显着抑制肿瘤的生长。

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 IC₅₀48小时后，与NSCLC（A549）细胞中的游离BQ相比。BQLC通过凋亡途径抑制细胞增殖，进一步抑制菌落形成和癌症转移in vitro。此外，与游离BQ相比，3D肿瘤仿真研究确定了凸体纳米载体的抗癌疗效。这是首次研究核子体的潜力，因为对重新利用药物的吸入疗法，BQ和结果表明，由于出色的雾化性能和增强的抗癌活性，BQLC可能是一种有希望的NSCLC治疗。

See the article

Suyash M. Patil, Shruti S. Sawant, Nitesh K. Kunda,
可吸入bedaquiline -loaded cubosomes for the treatment of non-small cell lung cancer (NSCLC),
国际药品杂志，第607、2021、20146卷，ISSN 0378-5173，
https://doi.org/10.1016/j.ijpharm.2021.121046.