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Synthesis and Characterization of PLGA-PEG Thymoquinone Nanoparticles and Its Cytotoxicity Effects in Tamoxifen-Resistant Breast Cancer Cells

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Cancer Biology and Advances in Treatment

Part of the book series: Advances in Experimental Medicine and Biology ((ICRRM,volume 1292))

Abstract

Introduction: Drug resistance has been a continuous challenge in cancer treatment. The use of nanotechnology in the development of new cancer drugs has potential. One of the extensively studied compounds is thymoquinone (TQ), and this work aims to compare two types of TQ-nanoformulation and its cytotoxicity toward resistant breast cancer cells.

Method: TQ-nanoparticles were prepared and optimized by using two different formulations with different drugs to PLGA-PEG ratio (1:20 and 1:7) and different PLGA-PEG to Pluronic F68 ratio (10:1 and 2:1). The morphology and size were determined using TEM and DLS. Characterization of particles was done using UV-VIS, ATR-IR, entrapment efficiency, and drug release. The effects of drug, polymer, and surfactants were compared between the two formulations. Cytotoxicity assay was performed using MTS assay.

Results: TEM finding showed 96% of particles produced with 1:7 drug to PLGA-PEG were less than 90 nm in size and spherical in shape. This was confirmed with DLS which showed smaller particle size than those formed with 1:20 drug to PLGA-PEG ratio. Further analysis showed zeta potential was negatively charged which could facilitate cellular uptake as reported previously. In addition, PDI value was less than 0.1 in both formulations indicating monodispersed and less broad in size distribution. The absorption peak of PLGA-PEG-TQ-Nps was at 255 nm. The 1:7 drug to polymer formulation was selected for further analysis where the entrapment efficiency was 79.9% and in vitro drug release showed a maximum release of TQ of 50%. Cytotoxicity result showed IC50 of TQ-nanoparticle at 20.05 μM and free TQ was 8.25 μM.

Conclusion: This study showed that nanoparticle synthesized with 1:7 drug to PLGA-PEG ratio and 2:1 PLGA-PEG to Pluronic F68 formed nanoparticles with less than 100 nm and had spherical shape as confirmed with DLS. This could facilitate its transportation and absorption to reach its target. There was conserved TQ stability as exhibited slow release of this volatile oil. The TQ-nanoparticles showed selective cytotoxic effect toward UACC 732 cells compared to MCF-7 breast cancer cells.

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Abbreviations

ATR-IR:

Attenuated Total Reflectance-Infrared Spectroscopy

DLS:

Dynamic Light Scattering

EE:

Entrapment Efficiancy

ER:

estrogen receptor

HER2:

Human Epidermal Growth Factor Receptor 2

IC50:

Half maximal inhibitory concentration

MDR1:

Multidrug Resistance Protein 1

MRP4:

Multidrug Resistance-associated Protein 4

MTS:

3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium

PDI:

Polydispersity Index

RPMI:

Roswell Park Memorial Institute

TEM:

Transmission Electron Microscope

TQ:

thymoquinone

UV-VIS:

Ultraviolet-visible spectrophotometry

β-actin:

beta actin

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Authors and Affiliations

  1. Oncological and Radiological Sciences Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia

    Rozaina Ahmad & Shahrul Hamid

  2. School of Chemical Sciences, Universiti Sains Malaysia, Minden, Penang, Malaysia

    Noor Haida Mohd Kaus

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  1. Rozaina Ahmad
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  2. Noor Haida Mohd Kaus
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  3. Shahrul Hamid
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Correspondence to Shahrul Hamid .

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Editors and Affiliations

  1. Stem Cell Institute, University of Science, Vietnam National University, Ho Chi Minh, Vietnam

    Phuc Van Pham

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Ahmad, R., Kaus, N.H.M., Hamid, S. (2018). Synthesis and Characterization of PLGA-PEG Thymoquinone Nanoparticles and Its Cytotoxicity Effects in Tamoxifen-Resistant Breast Cancer Cells. In: Pham, P.V. (eds) Cancer Biology and Advances in Treatment. Advances in Experimental Medicine and Biology(), vol 1292. Springer, Cham. https://doi.org/10.1007/5584_2018_302

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