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Effect of Chemical Binding of Doxorubicin Hydrochloride to Gold Nanoparticles, Versus Electrostatic Adsorption, on the In Vitro Drug Release and Cytotoxicity to Breast Cancer Cells

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Abstract

Purpose

The selective delivery of chemotherapeutic agent to the affected area is mainly dependent on the mode of drug loading within the delivery system. This study aims to compare the physical method to the chemical method on the efficiency of loading DOX.HCl to GNPs and the specific release of the loaded drug at certain tissue.

Method

Bifunctional polyethylene glycol with two different functionalities, the alkanethiol and the carboxyl group terminals, was synthesized. Then, DOX·HCl was covalently linked via hydrazone bond, a pH sensitive bond, to the carboxyl functional group and the produced polymer was used to prepare drug functionalized nanoparticles. Another group of GNPs was coated with carboxyl containing polymer; loading the drug into this system by the means of electrostatic adsorption. Finally, the prepared system were characterized with respect to size, shape and drug release in acetate buffer pH 5 and PBS pH 7.4 Also, the effect of DOX.HCl loaded systems on cell viability was assessed using MCF-7 breast cancer cell line.

Results

The prepared nanoparticles were spherical in shape, small in size and monodisperse. The release rate of the chemically bound drug in the acidic pH was higher than the electrostatically adsorbed one. Moreover, both systems show little release at pH 7.4. Finally, cytotoxicity profiles against human breast adenocarcinoma cell line (MCF-7) exhibited greater cytotoxicity of the chemically bound drug over the electrostatically adsorbed one.

Conclusion

Chemical binding of DOX·HCl to the carboxyl group of PEG coating GNPs selectively delivers high amount of drug to tumour-affected tissue which leads to reducing the unwanted effects of the drug in the non-affected ones.

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Abbreviations

AIBN:

Azobisisobutronitrile

ANOVA:

Analysis of variance

DCM:

Dichloromethane

DOX·HCl :

Doxorubicin HCl

DMSO:

Dimethyl sulfoxide

EPR:

Enhanced permeability and retention

GNPs:

Gold nanoparticles

HAuCl4.3 H3O:

Hydrogen tetrachloroauric acid trihydrate

IC50 :

The concentration of substance required for 50% growth inhibition

MCF-7:

Breast cancer cell line

MDR:

Multi-drug resistance

MWCO:

Molecular weight cut off

PCS:

Photon correlation spectroscopy

PDI:

Polydispersity index

P-gp:

P-glycoprotein

PBS:

Phosphate buffered saline

PEG:

Polyethylene glycol

RES:

Reticulo-endothelial system

SPR:

Surface plasmon resonance

TEM:

Transmission electron microscope

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt

    Gamal M. Zayed, Wael A. Abdelhafez, Fahd M. Alsharif & Ahmed M. Abdelsalam

  2. Al-Azhar Centre of Nanosceinecs and Applications (ACNA), Assiut, Egypt

    Gamal M. Zayed

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Port Said University, Port Fouad, Egypt

    Islam Kamal

  4. Department of Pharmaceutics, Qassim University, Qassim, Kingdom of Saudi Arabia

    Mohamed A. Amin

  5. Department of Pharmaceutical Chemistry, Al-Azhar University, Assiut, Egypt

    Montaser Sh. A. Shaykoon

  6. Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt

    Hatem A. Sarhan

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  1. Gamal M. Zayed
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  2. Islam Kamal
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  3. Wael A. Abdelhafez
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Correspondence to Gamal M. Zayed.

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Zayed, G.M., Kamal, I., Abdelhafez, W.A. et al. Effect of Chemical Binding of Doxorubicin Hydrochloride to Gold Nanoparticles, Versus Electrostatic Adsorption, on the In Vitro Drug Release and Cytotoxicity to Breast Cancer Cells. Pharm Res 35, 112 (2018). https://doi.org/10.1007/s11095-018-2393-6

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