Biodistribution of Curcumin and Its Derivatives: New Aspects for Curcumin Administration

摘要

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including antioxidant, anti-inflammatory, antitumor and chemo-protective effects. However, its clinical applications were initially limited by its poor absorption, rapid metabolism and rapid systemic elimination. To improve the bioavailability of curcumin, new approaches have to be taken. Three curcumin derivatives (mPEG_(2k)-Gly-Cur, mPEG_(2k)-Gly-Cur-OA and Cur-OA_2) were synthesized in this paper, and their biodistribution was analyzed by HPLC technique. In mice, all compounds were administered i.v. (equal to free curcumin 20 mg/kg), and the results confirmed the rapid clearance of free curcumin in blood and liver, but it was beyond our expectation to observe the remarkable lung tissue accumulation effect of curcumin, with C_(max)= 193.12 μg/g after 30 min of administration, and can still be detected with 8.25 μg/g after 4 h. PEGylation can extend the circulation half-life of curcumin, but the effect was limited attributed to the low molecular weight of PEG. PEG co-modify with Oleic acid can increase liver uptake of curcumin. Oleic acid alone esterified curcumin can significantly increase curcumin level in liver, and can be detected with 15.77 μg/g after 4 h. In conclusion, our finding suggested that free curcumin have the lung accumulation property, which implied lung disease therapeutic effect; and it would also be suitable for curcumin to explore pulmonary delivery system so as to increase its bioavailability. Additionally, Oleic acid esterification method could be another way to enhance curcumin activity in certain specific organs, especially in liver.