Preclinical Evidence

Distribution and Metabolism of Lipocurc™ (Liposomal Curcumin) in Dog and Human Blood Cells: Species Selectivity and Pharmacokinetic Relevance
Anticancer Res.2017 Jul;37(7):3483-3492
Liposomal curcumin is a nano-formulation (contains 6 mg/mL) that was developed for parenteral administration. Studies have revealed marked species differences of the plasma disposition of curcumin and its active metabolite Tetrahydrocurcumin (THC). Curcumin is known to interact with the blood cells, however, the impact of this interaction on its plasma pharmacokinetics is not known. The liver is the key metabolic site for curcumin. Former studies have shown that THC, a reductive active metabolite of curcumin, was measured in the plasma of whole blood incubated with liposomal curcumin.
Objective:

To investigate and compare the disposition of liposomal curcumin (Lipocurc™) and its major metabolite THC in blood cells. For comparison, the cellular distribution of curcumin was also investigated in cryopreserved hepatocytes from Beagle dogs and humans.

Methodology:

Curcumin (~2 µM) was incubated at 37°C for 15 min individually with red blood cells (RBCs), peripheral blood mononuclear cells (PBMCs), and hepatocytes obtained from male Beagle dog and male human donor sources.

Results and Discussion:
  • Blood cell distribution, metabolism of liposomal curcumin and factors impacting the pharmacokinetics of curcumin were observed successfully in this study
  • Species difference was noted between the distribution of curcumin and THC in blood cells from Beagle dog and human
  • Concentrations of curcumin were significantly higher in human RBCs and hepatocytes than that of the dogs, while it was opposite for PMBCs; higher in dog cells than that of the human cells
  • The measurement of THC in RBCs and PBMCs suggest that during the incubation period curcumin must have entered these cells and metabolized there to THC
  • The levels of THC were significantly higher in dog RBCs and PBMCs compared to human, while it was opposite for hepatocytes; higher in human cells than dog cells. This suggests the higher presence of reductase activity in dog RBCs and PBMCs as well as human hepatocytes
  • The ratio of THC to curcumin found in the RBC medium following incubation of 15 minutes was significantly higher for dog (6.3) compared to human (0.006), while there was no such marked species difference for PBMCs and hepatocytes.

The in vitro results obtained in this study were compared with in vivo data from published studies done in Beagle dogs and phase I human trials with liposomal curcumin. It was found that there was a very good correlation between the species differences of RBC metabolism of curcumin to THC and in vivo plasma levels of curcumin and THC from human studies.

Conclusion

There were species dependence and an excellent correlation between the in vitro disposition of curcumin and THC following incubation with RBCs and in vivo plasma levels of curcumin and THC in dog and human following intravenous infusion.