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Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

Authors
  • Andrgie, Abegaz Tizazu1
  • Birhan, Yihenew Simegniew1
  • Mekonnen, Tefera Worku1
  • Hanurry, Endiries Yibru1
  • Darge, Haile Fentahun1
  • Lee, Rong-Ho
  • Chou, Hsiao-Ying1
  • Tsai, Hsieh-Chih1, 2
  • 1 (H.-Y.C.)
  • 2 Advanced Membrane Materials Center, National Taiwan University of Science and Technology, Taipei 106, Taiwan
Type
Published Article
Journal
Polymers
Publisher
MDPI AG
Publication Date
Dec 27, 2019
Volume
12
Issue
1
Identifiers
DOI: 10.3390/polym12010043
PMID: 31892144
PMCID: PMC7023610
Source
PubMed Central
Keywords
License
Green

Abstract

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.

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