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 output: Contribution to journalJournal articlepeer-review

8 Scopus citations

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.

Original languageEnglish
Article number112
JournalPharmaceutical Research
Volume35
Issue number6
DOIs
StatePublished - 1 Jun 2018

Keywords

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

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