Modification of curcumin with polyethylene glycol enhances the delivery of curcumin in preadipocytes and its antiadipogenic property.

Conjugation of curcumin (CCM) by polyethylene glycol (PEG) has been previously developed to improve water solubility of the natural form of CCM and its antiproliferative role in some human cancer cell lines. This study examined the cellular uptake kinetics of the natural form of CCM and CCM-PEG. Their cytotoxic effect in proliferating preadipocytes and antiadipogenic property in differentiating preadipocytes had also been investigated. CCM and CCM-PEG were found to be differently absorbed in 3T3-L1 preadipocytes and adipocytes with a limited amount of CCM-PEG absorption in the cell. The improved water solubility of CCM-PEG was correlated with increased cellular retention of CCM in 3T3-L1 cells, particularly in preadipocytes. Consequently, CCM-PEG treatment sensitized proliferating preadipocytes to CCM-induced cell toxicity. Furthermore, incubation of differentiating 3T3-L1 cells with CCM-PEG resulted in improvement of the inhibitory role of CCM in adipocyte differentiation with no toxic effect. These results suggest that pegylation-improved water solubility and cellular retention of CCM may be uniquely useful for improving the delivery of CCM in preadipocytes and its antiadipogenic ability.