Liver uptake & ADMET studies

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Drug interactions with cultured cells

By using D’Liver’s specialised expertise in isolating highly purified freshly prepared cultures of hepatocytes, Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs), we can effectively and reliably determine the interaction with the compound. This assay enables a time and cost effective comparison of interaction profiles of several compounds in the same cell system.

For the study of intact liver cell uptake function, freshly isolated liver cells can not be replaced by any commercial available cell line. No commercial cell lines are able to maintain the highly specific liver uptake mechanisms in cell culture. 

LSEC

The major cell type responsible for liver metabolism of biopharmaceutical compounds are most often not hepatocytes, but the lesser known liver sinusoidal endothelial cells (LSECs). Consequently, any liver metabolism studies need to include the LSEC in order to reveal the complete interaction of biopharmaceuticals with liver cells.

Human liver cells - our speciality

D’Liver performs analyses with freshly isolated human hepatocytes, Kupffer cells and Liver sinusoidal endothelial cells. We isolate Kupffer cells and liver sinusoidal endothelial cells to a purity of >90%. These cells, isolated by us on a short time scale, maintain their remarkable physiological scavenger function. Of note, primary LSECs kept in cultures for more than a day, even under optimal conditions, lose their characteristic scavenger function. Moreover, replated “primary LSECs" or cell lines originating from primary LSECs, are useless in studies on LSEC scavenger function.

 

Assays

  • Liver cell type(s) responsible for uptake
  • Metabolic fate/degradation
  • Toxicological effects on LSECs, KCs and hepatocytes
  • Labelling of compound(s) with radioisotopes and/or fluorochromes

Key benefits and features

  • Identifying the compound(s) most likely to pass thorough the liver without being metabolized
  • Compare interaction profiles of several compounds in the same cell system
  • Time and cost effective
  • We use only cells that have been freshly prepared from intact liver
  • Encompass all three major liver cell types
  • Analyse native compounds or compounds labelled with 3H, 13C, 14C, 15N, 125I and/or fluorochromes
  • Studies will be tailored to our customers’ specific requirements
  • Swift response to requests
  • Quality in execution and delivery