Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Parvathaneni, Vineela; Elbatanony, Rasha S.; Goyal, Mimansa; Chavan, Tejashri; Vega, Nathan; Kolluru, Srikanth; Muth, Aaron; Gupta, Vivek; Kunda, Nitesh K.

doi:10.3390/ijms22094783

Open AccessArticle

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

by

Vineela Parvathaneni

¹

,

Rasha S. Elbatanony

^1,2,

Mimansa Goyal

¹,

Tejashri Chavan

¹,

Nathan Vega

³,

Srikanth Kolluru

³,

Aaron Muth

¹,

Vivek Gupta

^1,*

and

Nitesh K. Kunda

^1,*

¹

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA

²

Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt, Cairo 11835, Egypt

³

School of Pharmacy and Health Sciences, Keck Graduate Institute, 535 Watson Dr, Claremont, CA 91711, USA

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(9), 4783; https://doi.org/10.3390/ijms22094783

Submission received: 25 February 2021 / Revised: 20 April 2021 / Accepted: 28 April 2021 / Published: 30 April 2021

(This article belongs to the Special Issue Pulmonary Delivery of Drugs and Biologics)

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Abstract

There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 10³-fold after complexation with SBE-β-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-β-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC₅₀ values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.

Keywords: bedaquiline; sulfobutylether-β-cyclodextrin; non-small cell lung cancer; inhalation; molecular docking

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MDPI and ACS Style

Parvathaneni, V.; Elbatanony, R.S.; Goyal, M.; Chavan, T.; Vega, N.; Kolluru, S.; Muth, A.; Gupta, V.; Kunda, N.K. Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes. Int. J. Mol. Sci. 2021, 22, 4783. https://doi.org/10.3390/ijms22094783

AMA Style

Parvathaneni V, Elbatanony RS, Goyal M, Chavan T, Vega N, Kolluru S, Muth A, Gupta V, Kunda NK. Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes. International Journal of Molecular Sciences. 2021; 22(9):4783. https://doi.org/10.3390/ijms22094783

Chicago/Turabian Style

Parvathaneni, Vineela, Rasha S. Elbatanony, Mimansa Goyal, Tejashri Chavan, Nathan Vega, Srikanth Kolluru, Aaron Muth, Vivek Gupta, and Nitesh K. Kunda. 2021. "Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes" International Journal of Molecular Sciences 22, no. 9: 4783. https://doi.org/10.3390/ijms22094783

APA Style

Parvathaneni, V., Elbatanony, R. S., Goyal, M., Chavan, T., Vega, N., Kolluru, S., Muth, A., Gupta, V., & Kunda, N. K. (2021). Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes. International Journal of Molecular Sciences, 22(9), 4783. https://doi.org/10.3390/ijms22094783

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Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

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