Elsevier

Food Chemistry

Volume 119, Issue 2, 15 March 2010, Pages 669-674
Food Chemistry

Enhanced in vitro anti-cancer activity of curcumin encapsulated in hydrophobically modified starch

https://doi.org/10.1016/j.foodchem.2009.07.018Get rights and content

Abstract

Curcumin is a natural polyphenolic compound with anti-oxidation, anti-inflammation, and anti-cancer properties. However, these benefits of curcumin suffer from its extremely low water solubility and bioavailability. In this study, we demonstrated that hydrophobically modified starch (HMS), a food-grade biopolymer, is able to form micelles and to encapsulate curcumin. Upon encapsulation, curcumin showed increased solubility by about 1670-folds. This may be due to the hydrophobic interaction and hydrogen bonding between curcumin and HMS, as suggested by results from infrared and fluorescence spectroscopy. The synchrotron small-angle X-ray scattering results indicated that the addition of curcumin did not alter the structure of HMS, whose radius of gyration remained at 14.1 ± 0.1 nm. Moreover, encapsulated curcumin revealed enhanced in vitro anti-cancer activity compared to free curcumin. This study provides a novel food-grade encapsulation formulation to increase the bioaccessibility of curcumin.

Introduction

One of the newest trends in food science and technology is functional food. According to the International Food Information Council (IFIC), functional food is defined as “foods that provide health benefits beyond basic nutrition” (Shibamoto et al., 2008, Vaclavik and Christian, 2008). In recent years, extensive research has been carried out to study the health promotion properties of different phytochemicals and to devise novel encapsulation materials and methods, trying to incorporate functional ingredients into foods (Pegg & Shahidi, 2007).

Among various functional food ingredients, polyphenols have attracted many researchers’ attention because of their anti-oxidant, anti-inflammatory, and anti-cancer properties (Chan et al., 1998, Huang et al., 1994, Sharma et al., 2005, Sreejayan and Rao, 1996). Together with some other plant-derived polyphenols, curcumin [bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione], which is extracted from plant turmeric (Curcuma longa), is among the best characterised polyphenols (Khanna, 1999). Since it has a strong yellowish colour, it is primarily used as a food colourant. Equally important, curcumin has a long history to treat inflammation and cancers in India and China (Joe, Vijaykumar, & Lokesh, 2004).

Curcumin functions as an anti-cancer agent by activating apoptosis signaling and inhibiting cell proliferation (Duvoix et al., 2005). On one hand, curcumin inhibits Bcl2 and activates Caspase 9 to induce apoptosis, and on the other hand, it blocks many cell proliferation signaling pathways, such as MAP kinase pathway, AKT pathway and mTOR pathways (Duvoix et al., 2005, Howitz and Sinclair, 2008, Joe et al., 2004, Syng-ai et al., 2004).

The application of curcumin as a health-promoting agent has been limited by its poor water solubility and bioavailability. While curcumin is dissolves in ethanol, acetone, chloroform, DMSO (dimethyl sulphoxide) and some other polar organic solvents, its solubility in pure water is estimated to be at most 11 ng/mL (Kaminaga et al., 2003). Even worse, once absorbed in human body, curcumin undergoes rapid degradation and excretion (Sharma et al., 2005).

Many approaches have been applied to increase the water solubility and/or bioavailability of food bioactives by methods such as emulsion, chemical modification and micelle encapsulation. The greatest loading capacity is achieved by using an oil in water (O/W) emulsion system. As reported, curcumin can be dissolved in hot soybean oil up to 1% (Sou, Inenaga, Takeoka, & Tsuchida, 2008). The curcumin O/W nanoemulsions using medium chain triacylglycerols as the oil phase, which contained 1% curcumin, showed significantly improved anti-inflammation activity (Wang et al., 2008).

In addition to emulsion system, cyclodextrin is also known to form inclusion complex with curcumin (Tang et al., 2002, Tomren et al., 2007, Tonnesen et al., 2002). Among different cyclodextrin variants, hydroxypropyl-γ-cyclodextrin (HPγCD) has the highest encapsulation capacity, and the water solubility of curcumin in 10% HPγCD can reach about 2 mg/mL (Tomren et al., 2007).

Additionally, chemical modification methods were also reported to increase the water solubility of curcumin. Glucose molecules have been conjugated onto curcumin molecule by either chemical reaction or by plant cell culture (Kaminaga et al., 2003). These glucose–curcumin prodrugs have much better solubility in water, and the solubility of curcumin 4′,4″-O-β-d-digentiobioside in water could reach as high as 240 mg/mL (Kaminaga et al., 2003).

Micellar encapsulation is another approach to increase the water solubility of nutraceuticals. Micelles can be formed by small molecular-weight surfactants, such as cetyltrimethylammonium bromide (CTAB) (Iwunze, 2004, Leung et al., 2008, Wang et al., 2006). Synthetic amphiphilic polymers, for example, PEO-b-PCL [poly(ethylene glycol)-block-poly(caprolactone)] and methoxy poly(ethylene glycol)-palmitate, were also reported to form polymer micelles to encapsulate curcumin (Ma et al., 2008, Sahu et al., 2008). The solubilisation capacity and loading efficiency have been extensively investigated. However, no food-grade polymers have been reported to encapsulate curcumin, which greatly limits the application of curcumin in functional food products.

In searching food-grade amphiphilic materials to encapsulate curcumin, we focused on hydrophobically modified starch (HMS), an abundant and low cost food ingredient synthesised with waxy maize and n-octenyl succinic anhydride (n-OSA) (Shaikh, Bhosale, & Singhal, 2006). HMS is widely used to encapsulate flavours during spray drying process (Krishnan et al., 2005, Shaikh et al., 2006, Soottitantawat et al., 2005a, Soottitantawat et al., 2005b, Xie et al., 2007). Since HMS is an amphiphilic polymer, we hypothesise that following the polymeric micellar encapsulation strategy, HMS is also able to form polymer micelles and to encapsulate curcumin. In this study, we demonstrated that HMS micelles greatly increased the water solubility of curcumin. Moreover, curcumin encapsulated in HMS micellar cores exhibited increased anti-cancer activity in vitro.

Section snippets

Materials

Curcumin was a generous gift from Sabinsa Corporation (Piscataway, NJ), which contains 85% curcumin, with 11% of demethoxycurcumin and 4% of bisdemethoxycurcumin (Wang et al., 2008). It was used without further purification. Hydrophobically modified starch (HMS) was obtained from National Starch and Chemical Company (Bridgewater, NJ) with a brand name of Hi-Cap 100. Pyrene, acetone and chloroform were purchased from Sigma–Aldrich (St. Louis, MO).

Determination of the critical aggregation concentration of HMS

The critical aggregation concentration (CAC) of

Capability of HMS to form polymer micelles

To demonstrate the ability of hydrophobically modified starch (HMS) to form polymer micelles, the pyrene fluorescent method was first used to determine the possible critical aggregation concentration (CAC) of HMS. The fluorescent spectrum of pyrene is sensitively affected by its microenvironment. When pyrene is in hydrophilic environment, one of its excitation peaks is at 334 nm. Once pyrene migrates into hydrophobic environment, such as the core portion of polymer micelles, this peak shifts

Discussion and conclusion

In this study, curcumin was encapsulated into polymer micelles formed by hydrophobically modified starch. Upon encapsulation, curcumin showed increased water solubility. As the peak position shifted in either infrared or fluorescence spectra, it was suggested that the microenvironment of curcumin was changed upon encapsulation, and there may be a hydrogen bonding interaction between curcumin and HMS.

Compared with other polymeric micelles used to encapsulate curcumin, the critical aggregation

Acknowledgements

This work was supported by United States Department of Agriculture National Research Initiative grant (2007-35603-17744). We thank Dr. Liang Guo of APS, Argonne National Laboratory for technical assistance in SAXS experiment.

References (37)

  • R.A. Sharma et al.

    Curcumin: The story so far

    European Journal of Cancer

    (2005)
  • A. Soottitantawat et al.

    Influence of emulsion and powder size on the stability of encapsulated d-limonene by spray drying

    Innovative Food Science and Emerging Technologies

    (2005)
  • A. Soottitantawat et al.

    Microencapsulation of l-menthol by spray drying and its release characteristics

    Innovative Food Science and Emerging Technologies

    (2005)
  • K. Sou et al.

    Loading of curcumin into macrophages using lipid-based nanoparticles

    International Journal of Pharmaceutics

    (2008)
  • M.A. Tomren et al.

    Studies on curcumin and curcuminoids XXXI. Symmetric and asymmetric curcuminoids: Stability, activity and complexation with cyclodextrin

    International Journal of Pharmaceutics

    (2007)
  • H.H. Tonnesen et al.

    Studies of curcumin and curcuminoids. XXVII. Cyclodextrin complexation: Solubility, chemical and photochemical stability

    International Journal of Pharmaceutics

    (2002)
  • X.Y. Wang et al.

    Enhancing anti-inflammation activity of curcumin through O/W nanoemulsions

    Food Chemistry

    (2008)
  • G. Began et al.

    Interaction of curcumin with phosphatidylcholine: A spectrofluorometric study

    Journal of Agricultural and Food Chemistry

    (1999)
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