Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Abstract

Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

Dual Interactions of Amphiphilic Gelatin Copolymer and Nanocurcumin Improving the Delivery Efficiency of the Nanogels

“…In some investigations, ethanol showed a fair estimate of the proportions of its keto-enol forms of curcumin [55]. Dichloromethane (DCM) is one of the best solvents to use in extraction as well as in nCur processing [56,57]. Regarding our screening experiments, the co-solvents (ethanol and DCM) were used to produce nCur in amphiphilic copolymer solutions under ultrasonic-assisted condition.…”

Curcumin and piperine supplementation of obese mice under caloric restriction modulates body fat and interleukin-1β

“…Then, small amount of Cur and CurG are absorbed from the small intestine, transported to the liver via the portal vein, and undergoes a further conjugation reaction by the phase 2 metabolism. After that, it circulates in the blood and reaches various organs [ 18 , 26 ]. These data support our previous observations that CurG is the major metabolite found in rodent plasma after administration of Cur [ 18 ].…”

“…After that, it circulates in the blood and reaches various organs [ 18 , 26 ]. These data support our previous observations that CurG is the major metabolite found in rodent plasma after administration of Cur [ 18 ]. We found no significant difference in CurG levels between groups supplemented with Cur alone or combined with Pip.…”

“…It has been reported that Pip can increase Cur bioavailability, but it is not known if this effect is a direct effect of Pip on Cur metabolism [ 7 ]. Thus, using a liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) system, we analyzed plasma samples from the mice treated with Cur or both Cur and Pip (Cur + Pip) [ 18 ]. Briefly, plasma (200 μL) was mixed with 400 μL of methanol by vortex and centrifuged at 5000 g for 15 min at 4 °C.…”

A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

“…However, the clinical application of Cur remains very limited due to its extremely poor aqueous solubility (≈11 ng/ml) 25 and low bioavailability 26 . Various approaches have been attempted to address the aforementioned problems of Cur including using biomaterials such as the polymeric micelles 27 28 29 30 , liposomes 31 32 33 , polymeric nanoparticles (NPs) 34 35 36 , and hydrogels 37 38 39 to deliver Cur.…”