A Kinetic Degradation Study of Curcumin in Its Free Form and Loaded in Polymeric Micelles
- 430 Downloads
Curcumin, a phenolic compound, possesses many pharmacological activities and is under clinical evaluation to treat different diseases. However, conflicting data about its stability have been reported. In this study, the kinetic degradation of curcumin from a natural curcuminoid mixture under various conditions (pH, temperature, and dielectric constant of the medium) was investigated. Moreover, the degradation of pure curcumin at some selected conditions was also determined. To fully solubilize curcumin and to prevent precipitation of curcumin that occurs when low concentrations of co–solvent are present, a 50:50 (v/v) aqueous buffer/methanol mixture was used as standard medium to study its degradation kinetics. The results showed that degradation of curcumin both as pure compound and present in the curcuminoid mixture followed first order kinetic reaction. It was further shown that an increasing pH, temperature, and dielectric constant of the medium resulted in an increase in the degradation rate. Curcumin showed rapid degradation due to autoxidation in aqueous buffer pH = 8.0 with a rate constant of 280 × 10-3 h-1, corresponding with a half–life (t1/2) of 2.5 h. Dioxygenated bicyclopentadione was identified as the final degradation product. Importantly, curcumin loaded as curcuminoid mixture in ω–methoxy poly (ethylene glycol)–b–(N–(2–benzoyloxypropyl) methacrylamide) (mPEG–HPMA–Bz) polymeric micelles and in Triton X–100 micelles was about 300–500 times more stable than in aqueous buffer. Therefore, loading of curcumin into polymeric micelles is a promising approach to stabilize this compound and develop formulations suitable for further pharmaceutical and clinical studies.
KEY WORDScurcumin degradation polymeric micelles stability
The authors are grateful for the support received from the Thailand Research Fund (TRF) through the Royal Golden Jubilee PhD Program (RGJ) Grant No. 5. G. CM/52/D. 2. IN. We thank the Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University and Faculty of Pharmacy, Chiang Mai University for their support.
- 2.Vogel H, Pelletier J. Curcumin—biological and medicinal properties. J Pharmacol. 1815;2:50–0.Google Scholar
- 8.Schneider C, Gordon ON, Edwards RL, Luis PB. Degradation of curcumin: from mechanism to biological implications. J Agric Food Chem. 2015;63(35):7606–14.Google Scholar
- 10.Garcea G, Berry DP, Jones DJ, Singh R, Dennison AR, Farmer PB, et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev. 2005;14(1):120–5.PubMedGoogle Scholar
- 16.Gordon O. Oxidative transformation of curcumin: products and reaction mechanisms. Nashville (NSH): Vanderbilt University; 2014. Dissertation.Google Scholar
- 24.Sandur SK, Pandey MK, Sung B, Ahn KS, Murakami A, Sethi G, et al. Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism. Carcinogenesis. 2007;28(8):1765–73.CrossRefPubMedGoogle Scholar
- 34.Yoshioka H, Sugiura K, Kawahara R, Fujita T, Makino M, Kamiya M, et al. Formation of radicals and chemiluminescence during the autoxidation of tea catechins. Agr Biol Chem Tokyo. 1991;55(11):2717–23.Google Scholar
- 36.Ozgen M, Reese RN, Tulio AZ, Scheerens JC, Miller AR. Modified 2,2-Azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) method to measure antioxidant capacity of selected small fruits and comparison to ferric reducing antioxidant power (FRAP) and 2,2‘-Diphenyl-1-picrylhydrazyl (DPPH) methods. J Agric Food Chem. 2006;54(4):1151–7.CrossRefPubMedGoogle Scholar