Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability

Kiew SF 1 , Ho YT 2 , Kiew LV 3 , Kah JCY 4 , Lee HB 1 , Imae T 5 Show all authors , Chung LY 6

Affiliations 

  • 1 Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 2 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, 117456, Republic of Singapore
  • 3 Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: lvkiew@um.edu.my
  • 4 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Centre for Life Sciences (CeLS), #05-01, 28 Medical Drive, 117456, Republic of Singapore; Department of Biomedical Engineering, National University of Singapore, 4 Engineering Drive 3, Blk E4, #04-08, 117583, Republic of Singapore
  • 5 Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei 10607, Taiwan, ROC; Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Section 4, Keelung Road, Taipei 10607, Taiwan, ROC
  • 6 Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: chungly@hotmail.com
Int J Pharm, 2017 Dec 20;534(1-2):297-307.
PMID: 29080707 DOI: 10.1016/j.ijpharm.2017.10.045

Abstract

We synthesized a dextrin (DEX)-conjugated graphene oxide (GO) nanocarrier (GO100-DEX) as a potential drug delivery system to respond to a tumor-associated stimulus, α-amylase, that has high permeability through the fenestrated endothelial barrier to the tumor site. At acidic pH and in the presence of α-amylase to simulate tumor conditions, GO100-DEX released a 1.5-fold higher amount of doxorubicin (DOX) than of GO100. Under the same conditions, the cytotoxic effects of GO100-DEX/DOX were 2-fold greater than those of free DOX and 2.9-fold greater than those of GO100/DOX. Employing an in vitro biomimetic microfluidic blood vessel model lined with human umbilical vein endothelial cells, we evaluated the tumor vasculature endothelial permeation of GO100-DEX and GO100 using dextrans of 10 and 70kDa for comparison and as standards to validate the microfluidic blood vessel model. The results showed that the permeabilities of GO100-DEX and GO100 were 4.3- and 4.9-fold greater than that of 70kDa dextran and 2.7- and 3.1-fold higher than that of 10kDa dextran, thus demonstrating the good permeability of the GO-based nanocarrier through the fenestrated endothelial barrier.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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