Development of pharmaceutically scalable inhaled anti-cancer nanotherapy – Repurposing amodiaquine for non-small cell lung cancer (NSCLC)

Parvathaneni, Vineela; Kulkarni, Nishant S.; Chauhan, Gautam; Shukla, Snehal K.; Elbatanony, Rasha S.; Patel, Brijeshkumar; Kunda, Nitesh K.; Muth, Aaron; Gupta, Vivek

doi:10.1016/j.msec.2020.111139

Cited by 33 publications

(24 citation statements)

References 56 publications

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“…Mass median aerodynamic diameter (MMAD) and geometric standard deviation, the crucial parameters for aerosol performance, were calculated by computing AL-Rem deposition at each stage of the NGI using log probability analysis (n = 3). The fine particle fraction (FPF) percentage was defined as the fraction of emitted dose (total amount of drug that exited the nebulizer) deposited in the NGI at each stage [ 14 ].…”

Section: Methodsmentioning

confidence: 99%

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Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatmentin vitro

et al. 2021

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Aim: To formulate an aerosolized nanoliposomal carrier for remdesivir (AL-Rem) against coronavirus disease 2019. Methods: AL-Rem was prepared using modified hydration technique. Cytotoxicity in lung adenocarcinoma cells, stability and aerodynamic characteristics of developed liposomes were evaluated. Results: AL-Rem showed high encapsulation efficiency of 99.79%, with hydrodynamic diameter of 71.46 ± 1.35 nm and surface charge of -32 mV. AL-Rem demonstrated minimal cytotoxicity in A549 cells and retained monolayer integrity of Calu-3 cells. AL-Rem showed sustained release, with complete drug release obtained within 50 h in simulated lung fluid. Long-term stability indicated >90% drug recovery at 4°C. Desirable aerosol performance, with mass median aerodynamic diameter of 4.56 ± 0.55 and fine particle fraction of 74.40 ± 2.96%, confirmed successful nebulization of AL-Rem. Conclusion: AL-Rem represents an effective alternative for coronavirus disease 2019 treatment.

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Section: Methodsmentioning

confidence: 99%

“…Pulmonary delivery would provide high lung concentrations, mitigate systemic exposure and toxicities and reduce dosing frequency [ 14 ]. Inhalation via nebulization is one approach that provides easy and convenient drug delivery for patients [ 15 ].…”

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confidence: 99%

Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatmentin vitro

et al. 2021

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“…The BDQ complex with 200 mM SBE-β-CD was evaluated for its cytotoxic effect in this study, as SBE-β-CD resulted in superior solubilization of BDQ and exhibited a stoichiometric ratio of 1:1 (Discussed in Section 2.2 ). The experiment was carried out using an MTT assay, as per established protocols utilized in our lab [ 61 , 62 , 63 ]. In brief, cells were seeded in tissue culture (TC) treated 96-well plates at a seeding density of 2500 cells/well, incubated overnight for adherence at 37 °C and 5% CO 2 , and treatments were added the next day at various concentrations (2.5, 5, 10, 25, and 50 µM) of BDQ and BDQ-CD.…”

Section: Methodsmentioning

confidence: 99%

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

Parvathaneni

Elbatanony

Goyal

et al. 2021

IJMS

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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.

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“…Therefore, an SLMs will probably mitigate against such expenses. The physicochemical properties of the SLMs such as small particle size, charge or surface modifications are very important as they might have also imparted on the penetration behavior of the formulations thereby supporting the work of Tchoryk et al 41 It can be ascertained that the SLMs were able to deliver the drugs to microparticulate core efficiently in therapeutic model ensuring their clinical use as demonstrated by Parvathaneni et al 42…”

Section: In Vivo Studiesmentioning

confidence: 62%

Formulation, In vitro and In vivo Evaluation of Sustained released Artemether-Lumefantrine-Loaded microstructured solid Lipid Microparticles (SLMs)

2021

TJNPR

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Development of pharmaceutically scalable inhaled anti-cancer nanotherapy – Repurposing amodiaquine for non-small cell lung cancer (NSCLC)

Cited by 33 publications

References 56 publications

Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatmentin vitro

Aerosolized nanoliposomal carrier of remdesivir: an effective alternative for COVID-19 treatmentin vitro

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

Formulation, In vitro and In vivo Evaluation of Sustained released Artemether-Lumefantrine-Loaded microstructured solid Lipid Microparticles (SLMs)

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