Formulation of Chitosan-Coated Brigatinib Nanospanlastics: Optimization, Characterization, Stability Assessment and In-Vitro Cytotoxicity Activity against H-1975 Cell Lines.

Randa Mohammed Zaki,Ahmed Alsaqr,Layla A. Al-Kharashi,Saad M. Alshahrani,Md Khalid Anwer,Munerah M. Alfadhel

doi:10.3390/ph15030348

Randa Mohammed Zaki, Ahmed Alsaqr + Show 4 more

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https://doi.org/10.3390/ph15030348

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Abstract

The purpose of the current study was to develop Brigatinib (BGT)-loaded nanospanlastics (BGT-loaded NSPs) (S1-S13) containing Span 60 with different edge activators (Tween 80 and Pluronic F127) and optimized based on the vesicle size, zeta potential (ZP), and percent entrapment efficiency (%EE) using Design-Expert® software. The optimum formula was recommended with desirability of 0.819 and composed of Span-60:Tween 80 at a ratio of 4:1 and 10 min as a sonication time (S13). It showed predicted EE% (81.58%), vesicle size (386.55 nm), and ZP (−29.51 mv). The optimized nanospanlastics (S13) was further coated with chitosan and further evaluated for Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), in vitro release, Transmission Electron Microscopy (TEM), stability and in-vitro cytotoxicity studies against H-1975 lung cancer cell lines. The DSC and XRD revealed complete encapsulation of the drug. TEM imagery revealed spherical nanovesicles with a smooth surface. Also, the coated formula showed high stability for three months in two different conditions. Moreover, it resulted in improved and sustained drug release than free BGT suspension and exhibited Higuchi kinetic release mechanism. The cytotoxic activity of BGT-loaded SPs (S13) was enhanced three times in comparison to free the BGT drug against the H-1975 cell lines. Overall, these results confirmed that BGT-loaded SPs could be a promising nanocarrier to improve the anticancer efficacy of BGT.

Highlights

Anticancer drugs are considered successful when they exhibit maximum activity at target cancer cells, that can be achieved by a targeted drug delivery system [3]
Nanomaterials are an optimal choice as a targeted delivery system for the delivery of anti-cancer drugs by electively localizing them in tumor cells, lowering the risk of harm to healthy cells
Brigatinib (BGT) is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that is used to treat a certain type of non-small cell lung cancer (NSCLC) by inhibiting an abnormal protein that causes cancer cells to multiply [5–7]

Summary

Introduction

Lung cancer is the second most common types of cancer in the United States and the main cause of cancer mortality. Nanomaterials are an optimal choice as a targeted delivery system for the delivery of anti-cancer drugs by electively localizing them in tumor cells, lowering the risk of harm to healthy cells. This reduces toxicity with increased efficacy [4]. Brigatinib (BGT) is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that is used to treat a certain type of non-small cell lung cancer (NSCLC) by inhibiting an abnormal protein that causes cancer cells to multiply [5–7] This slows or stops the spread of cancer cells [8]. It was approved by the Food and Drug Administration (FDA)

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