Zinc Oxide Composites of Doxorubicin in the Form of Coating, Composite Films and Gels with a High Antitumor Activity and Low Toxicity

Emma R Arakelova,Mkrtich A Yeranosyan,Susanna L Grigoryan,Stepan G Grigoryan,Flora G Arsenyan,Anahit A Mirzoian,Ashot M Khachatryan,Rafayel E Muradyan,Zoya M Farmazyan,Hrachik V Gasparyan

doi:10.4236/ns.2019.113008

Emma R Arakelova, Mkrtich A Yeranosyan + Show 8 more

Open Access

https://doi.org/10.4236/ns.2019.113008

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Abstract

This work is devoted to the formation doxorubicin (DOX) zinc oxide composites in the form of coating (DOX + ZnO), hydrogels and composite films of DOX with polyvinyl alcohol (DOX + PVA + ZnO) by DC-magnetron deposition of ZnO nanoscale particles (ZnO NPs) on their surfaces (DOX, DOX + PVA) with higher (two times and more) antitumor activity and considerable smaller toxicity at low doses of DOX in compositions compared to the initial drug. Using the methods of spectroscopy, atomic force microscopy (AFM), scanning electron microscopy (SEM) and X-ray Powder Diffraction (XRD), the role of ZnO NPs size on the antitumor activity of doxorubicin zinc oxide compositions is shown. AFM shows presence of many ZnO NPs on the surface DOX. A comparison of the FTIR spectra of DOX and its zinc oxide compositions has shown the presence of new bands of OH valence and deformation vibrations. It is possible to assume that interaction between ZnO and DOX takes place in the form of hydrogen bond, promoting the complexes formation. It is possible that both synergic and hydrogen-bonding ZnO with DOX increase the antitumor activity.

Highlights

The modification of known antitumor preparations for the purpose of reducing their system toxicity and side effects, as well as the development of new methods for target delivery of drugs are the most important tasks in oncology
This paper is devoted to the systematization of data on antitumor activity of zinc oxide composites of doxorubicin [24,25,26,27], based on facile technology for obtaining them in the form of coatings, gels and composite films, alternative to the traditional nanotubes, nanoparticles
The novelty of this work in comparison with the previous research is the presentation of the role of nanoscale ZnO nanoscale particles (ZnO NPs) sizes on antitumor activity of doxorubicin zinc oxide composites

Summary

INTRODUCTION

The modification of known antitumor preparations for the purpose of reducing their system toxicity and side effects, as well as the development of new methods for target delivery of drugs are the most important tasks in oncology. When transforming to the gas phase, the complex decomposes on the surface of solid substrates with deposition of initial compound, ZnO It is a chemical transport reaction (CTR), various modifications of which can receive wide acceptance in various areas of science and engineering. Recent investigations on deposition of thin zinc oxide films on surface of salicylidene amino acid chelates with expressed antioxidant and antitumor properties by DC magnetron sputtering of a zinc target, have shown that zinc oxide composites in the form of coatings and composite films with polyvinyl alcohol (PVA) reveal higher (by 2 and 2.5 times) antitumor activity and considerable lower toxicity in comparison with the initial compounds [22, 23]. Nanosize ZnO particles (ZnO NPs) were deposited on the surfaces of DOX by DC-magnetron sputtering of zinc targets for the purpose of antitumor drug delivery to the tumour tissue in the form of coatings, composite films and gels taking into account antioxidant and transport properties of zinc oxide. It is expected that the achievement of the above-mentioned objectives will lead to the formation of zinc oxide compositions of antitumor drug doxorubicin with high antitumor activity and low toxicity

Formation of Coating from DOX

Formation of Hydrogels from DOX

Formation of Composite Films from DOX

Characterization of DOX and Zinc Oxide Composites

RESULTS AND DISCUSSION

CONCLUSIONS