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Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent

Overview of attention for article published in International Journal of Nanomedicine, May 2017
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Title
Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent
Published in
International Journal of Nanomedicine, May 2017
DOI 10.2147/ijn.s137347
Pubmed ID
Authors

Mohamed Wehbe, Malathi Anantha, Minghan Shi, Ada Wai-yin Leung, Wieslawa Dragowska, Leon Sanche, Marcel Bally

Abstract

Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex. Here, we describe an injectable Cu(DDC)2 formulation prepared through a method that involves synthesis of Cu(DDC)2 inside the aqueous core of liposomes. Convection-enhanced delivery of a Cu(DDC)2 formulation prepared using 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/cholesterol liposomes into a rat model of F98 glioma engendered a 25% increase in median survival time relative to vehicle-treated animals. In a murine subcutaneous MV-4-11 model, treatment resulted in a 45% reduction in tumor burden when compared to controls. Pharmacokinetic studies indicated that the Cu(DDC)2 was rapidly eliminated after intravenous administration while the liposomes remained in circulation. To test whether liposomal lipid composition could increase Cu(DDC)2 circulation lifetime, a number of different formulations were evaluated. Studies demonstrated that liposomes composed of DSPC and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-(carboxy[polyethylene glycol]-2000) (95:5) enhanced Cu(DDC)2 concentrations in the circulation as reflected by a 4.2-fold increase in plasma AUC(0-∞) relative to the DSPC/cholesterol formulation. The anticancer activity of this Cu(DDC)2 formulation was subsequently evaluated in the MV-4-11 model. At its maximum tolerated dose, this formulation exhibited comparable activity to the DSPC/cholesterol formulation. This is the first report demonstrating the therapeutic effects of an injectable Cu(DDC)2 formulation in vivo.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 34 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 18%
Researcher 5 15%
Student > Doctoral Student 4 12%
Student > Bachelor 4 12%
Student > Master 4 12%
Other 5 15%
Unknown 6 18%
Readers by discipline Count As %
Medicine and Dentistry 7 21%
Chemistry 6 18%
Pharmacology, Toxicology and Pharmaceutical Science 4 12%
Biochemistry, Genetics and Molecular Biology 4 12%
Agricultural and Biological Sciences 2 6%
Other 7 21%
Unknown 4 12%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 November 2017.
All research outputs
#9,664,427
of 12,083,996 outputs
Outputs from International Journal of Nanomedicine
#1,866
of 2,384 outputs
Outputs of similar age
#206,634
of 284,717 outputs
Outputs of similar age from International Journal of Nanomedicine
#43
of 62 outputs
Altmetric has tracked 12,083,996 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,384 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 13th percentile – i.e., 13% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 284,717 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 62 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.