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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Int J Cancer. Author manuscript; available in PMC 2010 October 15.
Published in final edited form as:
PMCID: PMC2747637

Oral administration of heat-solubilized curcumin for potentially increasing curcumin bioavailability in experimental animals


The paper by Narayanan et al., 20091 demonstrating the protective effect of curcumin and resveratrol in prostate cancer gives an interesting insight regarding the use of phytochemical combination therapy. It is of interest to note that liposome encapsulated curcumin was used for in vivo experimental animal use in this study to resolve the bioavailability issue of curcumin, resulting from poor absorption.1

It is very likely that poor absorption is a consequence of the fact that curcumin is practically insoluble in water. Therefore, solubility is an important issue in in vitro and in vivo experiments. Here, we would like to point out that we have shown increased solubility of curcumin (12-fold) and turmeric (3-fold) by the use of heat.2

The treatment with heat did not destroy curcumin’s biological activity, as shown by its inhibition of 4-hydroxy-2-nonenal (HNE) mediated modification (80% inhibition of HNE-modification) of a multiple antigenic peptide3 substrate in an enzyme-linked immunosorbent assay4 that employed HNE-modification of a solid-phase antigen substrate. Mass-spectrometric (matrix assisted laser desorption ionization time of flight) and spectrophotometric (400-700 nm) analysis of curcumin solubilized by heat did not demonstrate any heat-mediated disintegration of curcumin.3,5 In addition, we have also shown that curcumin solubilized in mild alkali (pH 7.6, 130 μM) also significantly inhibited HNE-antigen modification.6 It has been shown that most of the curcumin (90%) in phosphate buffered sulfate and serum free media (pH 7.2, at 37°C) was broken down in 30 min.7 The treatment with heat, however, appears to protect curcumin from breaking down faster. Heat-solubilized curcumin amounts decreased 47% in 12 h compared to starting levels, and 67% in 72 h compared to starting levels.2

Curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) is the most active ingredient of turmeric obtained from the rhizome Curcuma longa.7 This yellow pigment is a polyphenol that has been shown to be efficaceous against a variety of diseases, including cancer.2,7-9

Several vehicles have been employed to deliver curcumin in vivo or topically. DMSO (dimethyl sulfoxide) has been used for curcumin administration in vivo.10 A combination of hydroxypropyl-beta-cyclodextrin and propylene glycol alginate have been found to be best with respect to solubility of curcumin and release from the vehicle11 for topical delivery of curcumin. Incorporation of curcumin in an oil-in-water microemulsion12 has also been used for topical application. Another group13 has shown the potential of poly(ethylene oxide)-b-poly(epsilon-caprolactone)micelles as an injectable formulation for efficient solubilization, stabilization, and controlled delivery of curcumin in in vitro studies. Kunwar et al.14 have attempted curcumin binding to albumin and the use of liposomes as vehicles to deliver curcumin to live cells.

For delivery of drugs in vivo or topically, water is indisputably the simplest and the most non-toxic vehicle, provided the drug is soluble in aqueous medium. We have already demonstrated a significant increase in solubility of curcumin in water. Here, we suggest the possibility of considering heat-solubilized curcumin15 for future in vivo and in vitro studies.


1. Narayanan NK, Nargi D, Randolph C, Narayanan BA. Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. Int J Cancer. 2009 Feb 6; [PubMed]
2. Kurien BT, Singh A, Matsumoto H, Scofield RH. Improving the solubility and pharmacological efficacy of curcumin by heat treatment. Assay Drug Dev Technol. 2007;5:567–76. [PubMed]
3. Kurien BT, Jackson K, Scofield RH. Immunoblotting of multiple antigenic peptides. Electrophoresis. 1998;19:1659–61. [PubMed]
4. Kurien BT, Scofield RH. In vitro modification of solid phase multiple antigenic peptides/autoantigens with 4-hydroxy-2-nonenal (HNE) provide ideal substrates for detection of anti-HNE antibodies and peptide antioxidants. J Immunol Methods. 2005;303:66–75. [PubMed]
5. Kurien BT, Scofield RH. Increasing the solubility of the nutraceutical curcumin by heat and inhibition of oxidative modification. Mol Nutr Food Res. 2009;53:308. [PubMed]
6. Kurien BT, Scofield RH. Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study. J Ethnopharmacol. 2007;110:368–73. [PubMed]
7. Aggarwal BB, Kumar A, Aggarwal MS, Shishodia S. Curcumin derived from turmeric (Curcuma longa): a spice for all seasons. In: Bagchi D, Preuss HG, editors. Phytochemicals in Cancer Chemoprevention. CRC Press; Boca Raton, FL: 2004. pp. 349–387.
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9. Kurien BT, Scofield RH. Curry spice curcumin and prostate cancer. Mol Nutr Food Res. 2009 In press. [PubMed]
10. Cao J, Liu Y, Jia L, Jiang LP, Geng CY, Yao XF, Kong Y, Jiang BN, Zhong LF. Curcumin attenuates acrylamide-induced cytotoxicity and genotoxicity in HepG2 cells by ROS scavenging. J Agric Food Chem. 2008;56:12059–63. [PubMed]
11. Hegge AB, Schüller RB, Kristensen S, Tønnesen HH. In vitro release of curcumin from vehicles containing alginate and cyclodextrin. Studies of curcumin and curcuminoides. XXXIII. Pharmazie. 2008;63:585–92. [PubMed]
12. Teichmann A, Heuschkel S, Jacobi U, Presse G, Neubert RH, Sterry W, Lademann J. Comparison of stratum corneum penetration and localization of a lipophilic model drug applied in an o/w microemulsion and an amphiphilic cream. Eur J Pharm Biopharm. 2007;67:699–706. [PubMed]
13. Ma Z, Haddadi A, Molavi O, Lavasanifar A, Lai R, Samuel J. Micelles of poly(ethylene oxide)-b-poly(epsilon-caprolactone) as vehicles for the solubilization, stabilization, and controlled delivery of curcumin. J Biomed Mater Res A. 2008;86:300–10. [PubMed]
14. Kunwar A, Barik A, Pandey R, Priyadarsini KI. Transport of liposomal and albumin loaded curcumin to living cells: an absorption and fluorescence spectroscopic study. Biochim Biophys Acta. 2006;1760:1513–20. [PubMed]
15. Kurien BT, Scofield RH. Heat-solubilized curcumin should be considered in clinical trials for increasing bioavailability. Clin Cancer Res. 2009;15:747. [PMC free article] [PubMed]