STUDIES ON BIOAVAILABILITY ENHANCEMENT OF CURCUMIN
Keywords:Curcumin, Structural analogues, Bioavailability, Antimicrobial activity
Objective: The objective of the present work was to improve aqueous solubility and in vivo bioavailability of curcumin and structural analogues of curcumin such as potassium, calcium, magnesium salts and nitro derivative.
Methods: Structural analogues of curcumin were prepared by reaction of curcumin with potassium chloride, magnesium chloride hexahydrate and calcium chloride dihydrate in a suitable solvent. The nitro derivative synthesized by treating curcumin with sulphuric acid and nitric acid. The prepared analogues were evaluated for melting behavior, solubility, UV spectrophotometry, partition coefficient, moisture content, cellular uptake, FTIR analysis, antimicrobial activity and in vivo bioavailability in the rat.
Results: Chemical modification of curcumin increased the saturation solubility to 11.6, 16.5, 21.5, 28.0 µg/ml in calcium salt, magnesium salt, potassium salt and nitro derivative respectively, against 8.6 µg/ml of curcumin. The analogues were chemically stable as curcumin analyzed by FTIR spectrophotometry. Increased cellular uptake, as well as enhanced antimicrobial activity, was demonstrated by modified curcumin analogues. Moreover, significant improvement in plasma levels was estimated with nitro derivative.
Conclusion: The present work recommends that nitration of curcumin improves aqueous solubility which may improve absorption and in vivo bioavailability.
Jayadi T, Widiasmoko B. Curcumin benefits as an antioxidant, anti inflammation and antiapoptosis ameliorate paracetamol toxicity. Asian J Pharm Clin Res 2018;15:1.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-18.
Rai A, Kumar A, Hasan S, Saeed S. Curcumin in oral mucosal lesions: an update. Asian J Pharm Clin Res 2019;12:32-43.
Venkatesan N, Punithavathi D, Arumugam V. Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol 2000;129:231-4.
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or premalignant lesions. Anticancer Res 2001;21:2895-900.
Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004;10:6847-54.
Itokawa H, Shi Q, Akiyama T, Morris Natschke SL, Lee KH. Recent advances in the investigation of curcuminoids. Chin Med 2008;3:11.
Tomren MA, Masson M, Loftsson T, Hjorth Tonnesen H. Studies on curcumin and curcuminoids XXXI. Symmetric and asymmetric curcuminoids: Stability, activity and complexation with cyclodextrin. Int J Pharm 2007;338:27-34.
Wahlang B, Pawar YB, Bansal AK. Identification of permeability-related hurdles in oral delivery of curcumin using the caco-2 cell model. Eur J Pharm Biopharm 2011;77:275-82.
Weber M, Hunsaker A, Gonzales M, Heynekamp J, Orlando A, Deck L, et al. TPA-induced up-regulation of activator protein-1 can be inhibited or enhanced by analogs of the natural product curcumin. Biochem Pharmacol 2006;72:928–40.
Pan M, Huang M, Lin K. Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos 1999;27:486-94.
Ireson C, Orr S, Jones J, Versschoyel R, Lim CR, luo L, et al. Characterization of metabolites of the chemo-preservative agent curcumin in human and rat hepatocytes and in rat in vivo, and evaluation of their ability to inhibit phorbol ester includes prostaglandin E2 production. Cancer Res 2001;61:1058-64.
Lao CD, Ruffin MT, Normolle D, Heath DD, Murray SI, Bailey JM, et al. Dose escalation of a curcuminoid. BMC Complement Altern Med 2006;6:10.
Teiten MH, Eifes S, Dicato M, Diederich M. Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment. Toxins 2010;2:128-62.
Mosley A, Liotta C, Snyder P. Highly active anticancer curcumin analogues. Adv Exp Med Biol 2007;59:77-103.
Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin-phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm 2007;330:155-63.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, Srinivas PS. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med 1998;64:353-6.
Li L, Braiteh FS, Kurzrock R. liposome-encapsulated curcumin: in vitro and in vivo effects on proliferation, apoptosis, signaling, and angiogenesis. Cancer 2005;104:1322-31.
Marczylo H, Verschoyle D, Cooke N, Morazzoni P, Steward P, Gescher J. Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine. Cancer Chemother Pharmacol 2007;60:171-7.
Shaikh J, Ankola D, Beniwal V, Singh D, Kumar N. Nanoparticle encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer. Eur J Pharm Sci 2009;37:223-30.
Yang Y, Lin LC, Tseng Y, Wang C, Tsai H. Oral bioavailability of curcumin in rat and the herbal analysis from curcuma longa by LC-MS/MS. J Chromatogr B Anal Technol Biomed Life Sci 2007;853:183-9.
Brian F, Antony H, Peter S, Austin T. Vogel textbook of practical organic chemistry (5th edition); 2012. p. 850-65.
Forbes R, York P, Davidson J. Dissolution kinetics and solubilities of p-aminosalicylic acid and its salts. Int J Pharm 1995;126:199-208.
Yan Y, Kim A, Kwak K, Yoo K, Yong S, Choi G. Enhanced oral bioavailability of curcumin via a solid lipid-based self-emulsifying drug delivery system using a spray-drying technique. Biol Pharm Bull 2011;34:1179-86.
Febriza A, Novarina V, Idrus H, Hatta M. The effects of curcumin and vitamin D combination as inhibitor toward salmonella typhi bacteria growth in vivo. Int J Appl Pharm 2019;11:1-5.
Hosmani A, Thorat Y. Synthesis and evaluation of nanostructured particles of salt of ketoconazole for solubility enhancement. Dig J Nanomater Bios 2011;3:1411-8.
Anand P, Kunnumakkara B, Newman A, Aggarwal B. Bioavailability of curcumin: problems and promises. Mol Pharm 2007;4:807-18.
Burgos Moron E, Calderon Montano M, Salvador J, Robles A, Lopez Lazaro M. The dark side of curcumin. Int J Cancer 2010;126:1771-5.