Jump to main content
Jump to site search

Issue 61, 2016
Previous Article Next Article

Nanoformulations of anticancer thiosemicarbazones to reduce methemoglobin formation and improve anticancer activity

Author affiliations

Abstract

Triapine is a promising anticancer thiosemicarbazone which was investigated in multiple clinical trials, where it was active against leukemia but not against solid cancers. This is probably based on insufficient drug levels in the tumor due to a short plasma half-life. Therefore, we encapsulated Triapine into polymeric nanoparticles and remote-loaded liposomes to improve the drug pharmacokinetics as well as targeted delivery. However, burst release of Triapine from both nanoformulations was observed, making the synthesis of two novel Triapine derivatives necessary in order to improve the remote-loading properties. Indeed, the encapsulation efficiency increased and for one derivative also the desired continuous drug release was in line with a strongly reduced cytotoxic activity against cancer cells. In vivo studies of this most promising formulation demonstrated a significant increase in survival of the animals compared to the free drug. Finally, we investigated drug-induced methemoglobin formation, a frequently observed side effect of thiosemicarbazones, which was completely prevented by the liposomal formulation.

Graphical abstract: Nanoformulations of anticancer thiosemicarbazones to reduce methemoglobin formation and improve anticancer activity

Back to tab navigation

Supplementary files

Publication details

The article was received on 23 Mar 2016, accepted on 01 Jun 2016 and first published on 02 Jun 2016


Article type: Paper
DOI: 10.1039/C6RA07659A
Citation: RSC Adv., 2016,6, 55848-55859
  • Open access: Creative Commons BY license
  •   Request permissions

    Nanoformulations of anticancer thiosemicarbazones to reduce methemoglobin formation and improve anticancer activity

    B. Fischer, K. Kryeziu, S. Kallus, P. Heffeter, W. Berger, C. R. Kowol and B. K. Keppler, RSC Adv., 2016, 6, 55848
    DOI: 10.1039/C6RA07659A

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements