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Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model

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Abstract

Purpose

Chemotherapy as an important tool for cancer treatment faces many obstacles such as multidrug resistance and adverse toxic effects on healthy tissues. Drug delivery systems have opened a new window to overcome these problems.

Methods

A polyelectrolyte carboxymethyl cellulose polymer as a magnetic nanocarrier was synthesized for enhancing delivery and uptake of doxorubicin in MCF7 breast cancer cells and decreasing the adverse toxic effects to healthy tissues.

Results

The physicochemical properties of developed nanocarrier showed that it can be used in drug delivery purposes. The efficiency of the delivery system was assessed by loading and release studies. Besides, biological assays including protein-particle interaction, hemolysis assay, cytotoxicity study, cellular uptake, and apoptosis analysis were performed. All results persuaded us to investigate the cytotoxic effects of nanocarrier in an animal model by determining the biochemical parameters attributed to organ injuries, and hematoxylin and eosin (H&E) staining for histopathological manifestations. We observed that the nanocarrier has no toxic effect on healthy tissues, while, it is capable of reducing the toxic side effects of doxorubicin by more cellular internalization.

Conclusion

Chemical characterizations and biological studies confirmed that developed nanocarrier with permanent cationic groups of imidazolium and anionic carboxylic acid groups is an effective candidate for anticancer drug delivery.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CK:

Creatine kinase

CMC:

Carboxymethyl cellulose

Cr:

Creatinine

DAPI:

4′,6-diamidino-2-phenylindole

DDS:

Drug delivery systems

DEE:

Drug encapsulation efficiency

DLE:

Drug loading efficiency

DLS:

Dynamic light scattering

DOX:

Doxorubicin

DSC:

Differential scanning calorimetry

EDTA:

Ethylenediaminetetraacetic acid

EDX:

Energy-dispersive X-ray spectroscopy

EPR:

Enhanced permeability and retention

FBS:

Fetal bovine serum

FTIR:

Fourier transform infrared PLGA

LDH:

Lactate dehydrogenase

MDR:

Multidrug resistance

MFI:

Mean fluorescent intensity

MNPs:

Magnetic nanoparticles

MTT:

3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphe-nyltetrazolium bromide

P-gp:

P-glycoprotein

RPMI-1640:

Roswell Park Memorial Institute 1640 growth medium

SEM:

Scanning electron microscopy

TEM:

Transmission Electron Microscopy

VSM:

Vibrating-sample magnetometer

Ur:

Urea

XRD:

X-ray diffraction

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Acknowledgments and Disclosures

We thank the Drug Applied Research Centre (DARC), Aging Research Institute, Physical Medicine and Rehabilitation Research Centre, Clinical Research Development Unit, Shohada Hospital, Tabriz University of Medical Sciences, Tabriz, Iran and Cellular and Molecular Research Centre, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran. The authors report no conflicts of interest.

Author information

Author notes

  1. Vahid Shafiei-Irannejad and Mahdi Rahimi contributed equally to this work

Authors and Affiliations

  1. Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Vahid Shafiei-Irannejad, Roshan Dinparast-isaleh & Saman Bahrambeigi

  2. Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Vahid Shafiei-Irannejad

  3. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdi Rahimi & Alireza Alihemmati

  4. Aging Research Institute, Physical Medicine and Rehabilitation Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran

    Mahdi Rahimi

  5. Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran

    Mahdi Rahimi, Salman Shojaei & Zarrin Ghasemi

  6. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Mojtaba Zarei & Bahman Yousefi

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  1. Vahid Shafiei-Irannejad
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Correspondence to Bahman Yousefi.

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Shafiei-Irannejad, V., Rahimi, M., Zarei, M. et al. Polyelectrolyte Carboxymethyl Cellulose for Enhanced Delivery of Doxorubicin in MCF7 Breast Cancer Cells: Toxicological Evaluations in Mice Model. Pharm Res 36, 68 (2019). https://doi.org/10.1007/s11095-019-2598-3

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