Issue 61, 2016

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

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

Supplementary files

Article information

Article type
Paper
Submitted
23 Mar 2016
Accepted
01 Jun 2016
First published
02 Jun 2016
This article is Open Access
Creative Commons BY license

RSC Adv., 2016,6, 55848-55859

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. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements