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Controlled quercetin release from high-capacity-loading hyperbranched polyglycerol-functionalized graphene oxide

Authors Islami M, Zarrabi A, Tada S, Kawamoto M, Isoshima T, Ito Y

Received 27 June 2018

Accepted for publication 9 August 2018

Published 5 October 2018 Volume 2018:13 Pages 6059—6071

DOI https://doi.org/10.2147/IJN.S178374

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster


Matin Islami,1 Ali Zarrabi,1 Seiichi Tada,2 Masuki Kawamoto,2,3 Takashi Isoshima,3 Yoshihiro Ito2,3

1Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 8174673441, Iran; 2Emergent Bioengineering Materials Research Team, RIKEN Center for Emergent Matter Science, Wako, Saitama 351-0198, Japan; 3Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan

Purpose: An efficient drug-delivery system was prepared based on graphene oxide using a facile and one-step strategy for controlling the release of anticancer drugs.
Methods: Fabrication of single-layer graphene oxide (GO) sheets was carried out by both modified and improved Hummers method. Biocompatible hyperbranched polyglycerol (HPG) was grafted on the surface of GO through the ring-opening hyperbranched polymerization of glycidol. Various ratios of GO and glycidol were used for polymer grafting. An anticancer drug, quercetin (Qu), was loaded into modified GO via noncovalent interactions.
Results: Polymer grafting on the surface of GO sheets was confirmed by results obtained from Fourier-transform infrared and Raman spectroscopy, thermogravimetric analysis, energy-dispersive X-ray and X-ray spectroscopy, scanning electron microscopy, and atomic force microscopy. It was revealed that polymerization increased d-spacing between the basal planes. In addition, as a hydrophilic polymer, HPG improved the stability and dispersion of GO sheets in biological solutions and endowed extra drug-loading capacity for the sheets. The effect of hyperbranched structure on drug loading and release was investigated by comparing drug loading and release for HPG-modified GO and linear PPO-modified GO. Our experiments indicated high drug-loading capacity (up to 185%), and excellent encapsulation efficiency (up to 93%) for HPG-GO compared to linear PO-grafted GO. The release profile of Qu under various pH levels exhibited controlled and sustained drug release without an initial burst effect for HPG-GO, suggesting that an acidic solution could facilitate drug release. HPG-GO did not show any cytotoxicity on the MCF7 cell line in different concentrations during 72 hours’ incubation. Uptake and entrance of HPG-GO into the cells were verified by determining the intracellular amount of Qu by high-performance liquid chromatography.
Conclusion: A combination of the unique properties of GO and the biodegradable polymer polyglycerol revealed high drug-loading capacity, pH-dependent drug release, and cytocompatibility with HPG-GO, thus introducing it as a promising nanocarrier for anticancer drug delivery.

Keywords: polyglycerol, graphene oxide, hyperbranched polymer, cancer cell

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