Pharmaceutical Research

, 35:112 | Cite as

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

  • Gamal M. Zayed
  • Islam Kamal
  • Wael A. Abdelhafez
  • Fahd M. Alsharif
  • Mohamed A. Amin
  • Montaser Sh. A. Shaykoon
  • Hatem A. Sarhan
  • Ahmed M. Abdelsalam
Research Paper



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.


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.


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.


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.

Key words

bifunctionalized PEG doxorubicin HCl electrostatic adsorption GNPs MCF-7 pH sensitive release 





Analysis of variance




Doxorubicin HCl


Dimethyl sulfoxide


Enhanced permeability and retention


Gold nanoparticles

HAuCl4.3 H3O

Hydrogen tetrachloroauric acid trihydrate


The concentration of substance required for 50% growth inhibition


Breast cancer cell line


Multi-drug resistance


Molecular weight cut off


Photon correlation spectroscopy


Polydispersity index




Phosphate buffered saline


Polyethylene glycol


Reticulo-endothelial system


Surface plasmon resonance


Transmission electron microscope

Supplementary material

11095_2018_2393_MOESM1_ESM.docx (1 mb)
ESM 1 (DOCX 1034 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gamal M. Zayed
    • 1
    • 2
  • Islam Kamal
    • 3
  • Wael A. Abdelhafez
    • 1
  • Fahd M. Alsharif
    • 1
  • Mohamed A. Amin
    • 4
  • Montaser Sh. A. Shaykoon
    • 5
  • Hatem A. Sarhan
    • 6
  • Ahmed M. Abdelsalam
    • 1
  1. 1.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyAl-Azhar UniversityAssiutEgypt
  2. 2.Al-Azhar Centre of Nanosceinecs and Applications (ACNA)AssiutEgypt
  3. 3.Department of Pharmaceutics and Industrial Pharmacy, Faculty of PharmacyPort Said UniversityPort FouadEgypt
  4. 4.Department of PharmaceuticsQassim UniversityQassimKingdom of Saudi Arabia
  5. 5.Department of Pharmaceutical ChemistryAl-Azhar UniversityAssiutEgypt
  6. 6.Department of Pharmaceutics, Faculty of PharmacyMinia UniversityMiniaEgypt

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