Microencapsulation stabilizes curcumin for efficient delivery in food applications

Food Packaging and Shelf Life 10 (2016) 79–86

Contents lists available at ScienceDirect

Food Packaging and Shelf Life journal homepage: http://www.elsevier.com/locate/fpsl

Microencapsulation stabilizes curcumin for efficient delivery in food applications Isuru R. Ariyarathna, D. Nedra Karunaratne* Department of Chemistry, University of Peradeniya, Peradeniya, Sri Lanka

A R T I C L E I N F O

Article history: Received 10 September 2015 Received in revised form 8 August 2016 Accepted 20 October 2016 Available online xxx Keywords: Bioavailability Curcumin Encapsulation Photodegradation Chickpea protein Slow release carrier

A B S T R A C T

Curcumin has been identified as a remarkable cure for several types of ailments and its usage in food and pharmaceutical industry is plenteous. This study elucidates a promising method to encapsulate curcumin in a chickpea (Cicer arietinum) protein matrix to improve the stability and bioavailability in the gut. The technique uses isoelectric precipitation of chickpea protein that results in formation of microparticles. Release of curcumin from the protein matrix was slow at pH 4, and a burst release of nearly 100% was observed at pH 2. Protective capacity of curcumin, by the coating is more than 40% at 323 K and 25% at both 298 and 310.5 K. Protein matrix reduced the photodegradation of curcumin by 60%. Due to these properties the capsules can be used in the food industry as a protective coating for curcumin and as a slow release carrier in pharmaceutical industry. ã 2016 Elsevier Ltd. All rights reserved.

1. Introduction Turmeric (Curcuma longa) has been used to treat sprains, wounds, pulmonary, gastrointestinal, and liver disorders in traditional Asian medicine. Scientists have identified curcumin to be the active ingredient in turmeric rhizome that is responsible for its medicinal properties (Sharma, Gescher, & Steward, 2005). Curcumin is a polyphenolic diketone present approximately 1–6% in turmeric (Tayyem, Heath, Al-Delaimy, & Rock, 2006). Curcumin is used in many pharmaceutical applications due to its remarkable properties such as anticarcinogenicity, antimicrobial, antidiabetic, antioxidant, antivenom, hypocholesteremic, anti-tumor, and antiHIV (Jurenka, 2009; Kulkarni, Dhir, & Akula, 2009; Shrishail, Handral, Handral, Tulsianand, & Shruthi, 2013). Further clinical trials attest that curcumin doses are nontoxic up to 10 g/day (Aggarwal, Kumar, & Bharti, 2003; Singh, Wahajuddin, & Jain, 2010). Curcumin is hydrophobic and has low solubility in aqueous media (Aziz et al., 2013). Previous studies have concluded that rapid systemic elimination, less absorption, and rapid metabolism of curcumin lowers its bioavailability in human body (Anand, Kunnumakkara, Newman, & Aggarwal, 2007). To overcome this problem, various methods and coatings that are associated with

* Correspondance to: Department of Chemistry, University of Peradeniya, Peradeniya, Sri Lanka. E-mail address: [email protected] (D. N. Karunaratne). http://dx.doi.org/10.1016/j.fpsl.2016.10.005 2214-2894/ã 2016 Elsevier Ltd. All rights reserved.

encapsulating curcumin have been used (Dhule et al., 2012; Mukerjee & Vishwanatha, 2009; Tsai, Chien, Lin, & Tsai, 2011). The success and efficiency of the curcumin formulations have been confirmed via clinical trials in rats (Mythri, Jagatha, Pradhan, Andersen, & Bharath, 2007; Tsai et al., 2011). Further there are records of usage of biodegradable and biocompatible substances like poly(lactic-co-glycolic acid) to improve curcumin formulations (Park, 1995). Due to poor stability under light, heat, enzymes, and alkalinity, wide usage of curcumin in pharmaceutical and food industry has posed difficulties (Sharma et al., 2005; Zebib et al., 2010). Encapsulation of curcumin to overcome these drawbacks might be the solution to this problem. In literature different types of proteins are incorporated in microencapsulation processes (Heidebach, Först, & Kulozik, 2009; Solanki et al., 2013; Weinbreck, Minor, & de Kruif, 2004). Chickpea protein holds advantages like biodegradability, biocompatibility, and non-toxicity over most of other vehicles such as ZnO, TiO2, and Au in encapsulation field (Ariyarathna & Karunaratne, 2015; Karunaratne et al., 2016; N. Murawala, Tirmale, Shiras, & Prasad, 2014; Puvvada et al., 2015). Further proteins are generally recognized as safe in food applications and do not cause toxicity or side reactions (van der Spiegel, Noordam, & van der Fels-Klerx, 2013). Whey proteins and soy proteins have been used as carrier vessels to entrap drugs and nutrients while chickpea protein is less used. Chickpea protein can be an alternative protein to overcome this limitation due to its high protein content (25%) and due to its high digestibility (95%) (Sánchez-Vioque, Clemente, Vioque,

80

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

Bautista, & Millán, 1999). Currently many techniques of microencapsulation are available. Depending on the matrix, methods such as coacervation, interfacial polymerization, in situ polymerization, poly condensation, fluidized bed coating, and isoelectric precipitation technique may be used for microencapsulation (Ariyarathna & Karunaratne, 2015; Jyothi et al., 2010). For plant proteins, spray drying and coacervation are the methods of choice (Jun-xia, Haiyan, & Jian, 2011; Tang and Li, 2013). Further cold gelation and spray drying techniques are preferred when microencapsulating with animal proteins (Subirade, Remondetto, & Beaulieu, 2003). In here, we report a method based on isoelectric precipitation technique to entrap curcumin in chickpea protein due to its simplicity, high yield, and less extensive utilization in the field of encapsulation. 2. Materials and methods Chickpeas and turmeric were purchased from Cargills supermarket, Kandy, Sri Lanka. HCl (analytical grade), NaOH, Ethanol, Hexane (chemical grade), NaCl, KH2PO4, CaCl2, KCl, and pepsin were purchased from Sigma Chemicals, St. Louis, MO, USA.

The quantification of the curcumin in each solution was carried out by measuring the concentration of curcumin by UV spectroscopy using a standard curcumin calibration curve of 1, 5, 10, 15, 20, and 25 mg L 1. Standards were prepared by dissolving curcumin in 5 mL of ethanol and diluting up to the relevant volume using deionized water. The wavelength of maximum absorption (l max) was observed at 427 nm and selected for the estimation. Absorbance values were measured using a Shimadzu-1800 instrument. 2.5. Loading capacity (LC) First loosely bound curcumin was removed by rapid shaking of the curcumin-encapsulate in dilute HCl (pH 4.5). Then the encapsulating system was broke open with 1 mol dm 3 HCl solution and the mass of curcumin entrapped in the protein was determined. The following equation was used for the calculation. LC = {[Curcumin]entrap  100/[Encapsulation system]tot} % Where [Curcumin]entrap and [Encapsulating system]tot are mass of curcumin trapped in the encapsulating system and initial mass of encapsulating system used respectively.

2.1. Chickpea protein isolation 2.6. Particle size analysis Chickpea seeds (200 g) were dry ground in to a fine powder and defatted in a Soxhlet extractor for 6 h using hexane. The defatted chickpea powder was suspended in 1 mol dm 3 NaOH (500 mL) solution and stirred for 30 min. Extract was taken out and acidified by 1 mol dm 3 HCl solution to the isoelectric point of the protein which is pH 4.5 to get maximum yield. The protein precipitate was recovered by centrifugation for 10 min at 8000  g at 273 K and dried using an Edwards freeze dryer (Sánchez-Vioque et al., 1999). 2.2. Curcumin isolation Dried turmeric rhizomes (50 g) were powdered, placed in a Soxhlet apparatus, and extracted using 200 mL of hexane for 2 h. The solvent was removed and the remaining powder was reextracted using methanol for 6 h. After the extraction, the brown colored extract was concentrated using a rotary evaporator, and freeze dried to get curcumin powder (Revathy, Elumalai, Benny, & Antony, 2011). 2.3. Method of curcumin encapsulation Chickpea protein (1 g) was dissolved in 50 mL of 1 mol dm 3 HCl solution followed by adding 0.1 g of curcumin in 5 mL ethanol and stirred to obtain a curcumin-protein homogenous solution. The solution was basified to isoelectric point (pH 4.5) using 1 mol dm 3 NaOH solution under stirring until a precipitate was observed. Dry particles were obtained by centrifuging the suspension at 8000  g for 10 min at 273 K followed by freeze drying using an Edwards freeze dryer (Ariyarathna & Karunaratne, 2015). 2.4. Encapsulation efficiency (EE) The supernatant from the centrifugation of the encapsulating system was collected from each trial. The amount of curcumin in the supernatant was quantified using UV absorbance spectroscopy (Shimadzu-1800 UV instrument). The following equation was used in the calculation: EE = {{[Curcumin]tot

[Curcumin]sup}  100/[Curcumin]tot} %

Where [Curcumin]tot and [Curcumin]sup are total curcumin used initially and of curcumin in supernatant respectively in moles.

A suspension was prepared by dispersing 0.2 g of the curcuminencapsulate in 10 mL, pH 4.5 phosphate buffer solution. Particle size was measured in triplicate by placing the suspension in a CILAS 1190 particle size analyzer. 2.7. FTIR characterization FTIR of curcumin, chickpea protein, and the curcuminencapsulate were taken by 4 cm 1 resolution ShimadzuIR Prestige-21 FTIR spectrophotometer. FTIR spectra were obtained by placing the sample pellet prepared by mixing each samples with fused KBr in a ratio of 1:100. 2.8. In vitro release A known mass of encapsulating system (0.1 g) was suspended in pH 2 phosphate buffer solution, inserted in to a dialysis bag and dialyzed against pH 2 phosphate buffer solution (fixed in a thermo stable water bath set at 310 K) under rapid stirring. At 30 min intervals, 3 mL aliquots of the dialyzate were removed, checked for absorbance at 427 nm and replaced. The percentage of curcumin released was determined from the equation. Percentage release = {[Curcumin]rel  100/[Curcumin]tot} % Where, [Curcumin]rel is the concentration of released curcumin collected at time t and [Curcumin]tot is the total mass of curcumin entrapped in the microparticles. The procedure was repeated for pH 2 simulated gastric juice in presence of pepsin (SGJP), pH 4, and pH 6 buffer media. Whole procedure was carried out in obscure light condition. SGJP was prepared by mixing NaCl (2.05 g L 1), KH2PO4 (0.60 g L 1), CaCl2 (0.11 g L 1), and KCl (0.37 g L 1), adjusted to pH 2 with 1 mol dm 3 HCl followed by adding pepsin (0.0133 g L 1) (Ariyarathna & Karunaratne, 2015). 2.9. Photodegradation study 2.0 g of curcumin slightly moistened by pH 4.5 HCl was exposed to a UV lamp (9 W, 240 V). Temperature was maintained at 298 K and portions of 0.01 g were weighed out from the sample on a weekly basis up to 8 weeks. Curcumin present in each sample was

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

measured by dissolving the sample in 100 mL HCl solution (pH 2) and measuring UV absorbance at 427 nm. The procedure was repeated for the encapsulating system. 2.10. Thermal degradation Curcumin, and the curcumin-encapsulate (0.5 g from each) were weighed separately and kept for a month at 298 K in dry and amber colored glass bottles. After one month, 0.01 g of each sample was placed in separate 250 mL volumetric flasks, dissolved in 10– 15 mL of HCl (pH 2, 10 2 M) and diluted up to the mark using deionized water. Curcumin degradation of each sample was determined using a UV spectrophotometer. The procedure was repeated at 333.5 K and 323 K for each sample. 2.11. Swelling experiment 0.1 g from the encapsulating system was placed in 50 mL test tube containing 10 mL of pH 4.5 HCl solution. At 30 min time intervals encapsulate was separated from the dispersing media, surfaces slightly dabbed using a tissue paper followed by weighing. Following equation was used to determine swelling ratio. Swelling ratio = [Ww

Wd]/ Wd

Where Ww and Wd are mass of wet encapsulating system at time t and mass of dry encapsulating system respectively. Same procedure was carried out at pH 4 and pH 5 media for the encapsulate.

81

2.13. Statistical analysis The encapsulation method, EE, LC, release study, photodegradation, and thermal degradation experiments were performed in triplicate and the results were expressed as mean  standard deviation (SD). “Origin 8” was used as the graphing software. 3. Results and discussion 3.1. Curcumin encapsulation In this study, curcumin microcapsules were obtained by isoelctric precipitation method by keeping the chickpea protein as the matrix. At the isoelectric point (pI) protein molecule has zero net charge, which drastically represses the solubility, while at pH values above or below this value, protein molecules are readily soluble. The method was carried out based on the idea that protein will trap small molecules present in the medium, when the pH of the solution is brought to the pI of the protein. Here in order to improve the EE of the method, a curcumin dissolved ethanol solution was mixed with the protein solution before pH adjustment. In the encapsulation step it is necessary to maintain the protein-curcumin solution at an acidic pH (<6.8) as curcumin readily degrades under basic conditions (Wang et al., 1997). Freeze dried encapsulate was observed under Scanning electron microscope (Fig. 1). 3.2. EE, LC, and particle size

2.12. Thermal gravimetric analysis (TGA) The relative change of weight of the microencapsulating system with respect to the change in temperature was studied by placing 5–7 mg of the encapsulating system in Universal V4.5A TA instrument, under temperature program from 303 K to 1273 K at 20 K min 1 in nitrogen atmosphere with a purge rate of 20 mL min 1.

In the encapsulation field EE and LC values are very important measurements related to the coating material. When the EE and LC values are high, the coating material is said to be more efficient to encapsulate a particular substance. In this experiment, EE and LC of the encapsulate was 78.6  2.3% and 9.2  1.8% respectively. The observed EE is more than 15% higher than an EE value that we reported in 2015, for the encapsulation of folate in chickpea

Fig. 1. Scanning electron microscopic images of the curcumin microencapsules.

82

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

Fig. 2. FTIR spectra of chickpea protein, encapsulate, and curcumin.

protein using the isoelectric precipitation technique. But the observed LC values are very similar in both studies (Ariyarathna & Karunaratne, 2015). We used pH 4.5 phosphate buffer solution to determine particle size distribution due to the reason that the encapsulate is stable and aggregation can be expected to be minimal. We found that the size distribution of capsules is in the micro range (1–20) mm. This particle size range is confirmed by the SEM studies that carried out on the curcumin-encapsulate.

3.3. FTIR characterization FTIR spectrum of curcumin (Fig. 2) shows characteristic absorption peaks at 800 cm 1, 960 cm 1, 1030 cm 1, 1275 cm 1, 1500 cm 1, 1650 cm 1, and 1650 cm 1 while absorption bands of protein appears at 1080 cm 1, 1245 cm 1, 1400 cm 1,1550 cm 1, and 1550 cm 1. FTIR of curcumin capsules resemble similar peak pattern as chickpea protein where the characteristic peaks of

Fig. 3. Release of curcumin at different pH media.

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

83

Fig. 4. Photodegradation of curcumin in the pure form and encapsulated form.

curcumin have been masked. It can be concluded that curcumin resides fully within the protein matrix. 3.4. In vitro curcumin release In this experiment encapsulating system showed a sustained release behavior and therefore the system can be used to increase bioavailability of curcumin in the gut. The burst release at pH 2 shown by the encapsulate reveals that almost 90% of curcumin is released in about 5 h time period. The release kinetics was high in pH 2 simulated gastric juice in the presence of pepsin compared to the pH 2 buffer without pepsin. This can be expected due to enzymatic degradation of the protein by pepsin which releases trapped curcumin to the medium. The encapsulating system showed a higher release at pH 2 and lowest at pH 4 (Fig. 3). Slow release kinetics can be observed when the pH of the medium is closer to the isoelectric point of the protein. Since the protein is least soluble at its isoelectric point, the curcumin stays trapped in the matrix and its release is much slower than at a pH above or below where the protein is more soluble thereby enabling the release from the matrix.

3.6. Thermal degradation Under high temperature exposure for a short time period during food processing caused for a considerable degradation of curcumin (Chen et al., 2014). However, curcumin shows a high degradation when stored for a long time period (Thakam & Saewan, 2014). This study elucidates the potential of the protein as a protective coating for curcumin on long term storage at different temperatures. Here we measured thermal degradation of curcumin of the encapsulate for a period of month. We observed that the degradation of curcumin at 323 K is 61.06  2.39% while that of the encapsulate is 19.35  2.79%. At 298 and 310.5 K curcumin protection by the protein coating was more than 20%. This clearly indicates a significant protection of curcumin during long term storage (Fig. 5).

3.5. Photodegradation study Curcumin is highly unstable when exposed to light especially in wet conditions. It has been found that photo-irradiation of curcumin leads to degradation products, vanillic acid, vanillin, ferulic acid feruloylmethane, and dimethyl ketone (Brittain, 2014; Griesser et al., 2011; Thakam & Saewan, 2014). This study attempts to understand the extent of degradation of curcumin in the encapsulating system under UV conditions. After 8 weeks of exposure, more than 80% curcumin underwent degradation while the encapsulate afforded a protective effect from light (Fig. 4). Thus, it can be concluded that the protein coating protects curcumin against photodegradation.

Fig. 5. Effect of temperature on degradation of curcumin in free form and in encapsulated form.

84

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

Fig. 6. Swelling ratio of the encapsulate at different pH media.

3.7. Swelling property Swelling is a characteristic of a polymeric matrix that significantly affects drug release property of an oral tablet

(Martínez-Ruvalcaba, Sánchez-Díaz, Becerra, Cruz-Barba, & González-Álvarez, 2009). In this study, the degree of swelling of the encapsulate was investigated at different pH (pH 4, 4.5, and 5) values to determine the influence of pH on swelling of the

Fig. 7. TGA of the encapsulate.

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

encapsulating system (Fig. 6). To prevent degradation of curcumin, swelling was studied only in acidic media. Protein has a bulky network which can allow the entry of small solvent molecules (Leitner et al., 2010). The system is in equilibrium once maximum absorption of a solvent takes place. In this study the observed high swelling ratio might be due to the formation of favorable inter molecular hydrogen bonds between protein and water molecules. Protein surfaces of the encapsulate can facilitate hydrogen bonding with water. For the encapsulate higher swelling was observed at pH 4.5 buffer media which is the isoelectric point of the chickpea protein. The minor disturbance of protein molecules at this particular pH may be the reason for the higher swelling. When the pH deviates from pH 4.5, protein molecules tends to dissolve and the number of protein molecules in the matrix that is capable of binding with water molecules via hydrogen bonding get reduced, lowering the swelling property. 3.8. Thermal gravimetric analysis (TGA) Capsules were subjected to thermal gravimetric analysis (Fig. 7). It showed minor weight loss (8.14%) at 344 K due to loss of water. Loss of weight at 583 K and 827 K in roughly equal amounts is accounted as degradation of the protein and organic material. The encapsulating system showed complete degradation without leaving any residual matters. Maximum degradation can be observed at 827 K. 4. Conclusions Encapsulation of drugs is a well studied area both in microand nanoscales while food related encapsulation has been mostly carried out in the microscale. In this study, we developed an encapsulating system that contains curcumin within a protein matrix. The method used, yielded an encapsulating system in the microscale. From this study, we deduced that encapsulation imparted protection to curcumin from heat and light. In addition the release of curcumin from the protein matrix was found to be pH dependent. The method showed promising release potential and improved stability of curcumin indicating that the encapsulating system is usable as a drug in pharmaceutics and as well as a protective coating in food manufacture. Since protein is biocompatible and has nutritional value, the encapsulating system can be considered as a multi-nutrient safe substance for human intake. Acknowledgement The authors wish to acknowledge The Sri Lanka Institute of Nanotechnology for performing the TGA and SEM. References Aggarwal, B. B., Kumar, A., & Bharti, A. C. (2003). Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Research, 23(1A), 363–398. Anand, P., Kunnumakkara, A. B., Newman, R. A., & Aggarwal, B. B. (2007). Bioavailability of curcumin: Problems and promises. Molecular Pharmaceutics. http://dx.doi.org/10.1021/mp700113r. Ariyarathna, I. R., & Karunaratne, D. N. (2015). Use of chickpea protein for encapsulation of folate to enhance nutritional potency and stability. Food and Bioproducts Processing, 95, 76–82. http://dx.doi.org/10.1016/j.fbp.2015.04.004. Aziz, M. T. A., El Ibrashy, I. N., Mikhailidis, D. P., Rezq, A. M., . . . Wassef, M. A. A. (2013). Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy. Diabetology & Metabolic Syndrome, 5(1), 13. http://dx.doi.org/10.1186/1758-5996-5-13. Brittain, H. G. (2014). Profiles of drug substances, excipients and related methodology. Elsevier Science Retrieved from https://books.google.com/books? id=8F4TAgAAQBAJ.

85

Chen, Z., Xia, Y., Liao, S., Huang, Y., Li, Y., He, Y., . . . Li, B. (2014). Thermal degradation kinetics study of curcumin with nonlinear methods. Food Chemistry, 155, 81–86. http://dx.doi.org/10.1016/j.foodchem.2014.01.034. Dhule, S. S., Penfornis, P., Frazier, T., Walker, R., Feldman, J., Tan, G., . . . Pochampally, P. (2012). Curcumin-loaded g-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. Nanomedicine: Nanotechnology, Biology, and Medicine, 8(4), 440–451. http://dx.doi.org/10.1016/ j.nano.2011.07.011. Griesser, M., Pistis, V., Suzuki, T., Tejera, N., Pratt, D. A., & Schneider, C. (2011). Autoxidative and cyclooxygenase-2 catalyzed transformation of the dietary chemopreventive agent curcumin. The Journal of Biological Chemistry, 286(2), 1114–1124. http://dx.doi.org/10.1074/jbc.M110.178806. Heidebach, T., Först, P., & Kulozik, U. (2009). Microencapsulation of probiotic cells by means of rennet-gelation of milk proteins. Food Hydrocolloids, 23(7), 1670–1677. http://dx.doi.org/10.1016/j.foodhyd.2009.01.006. Jun-xia, X., Hai-yan, Y., & Jian, Y. (2011). Microencapsulation of sweet orange oil by complex coacervation with soybean protein isolate/gum Arabic. Food Chemistry, 125(4), 1267–1272. http://dx.doi.org/10.1016/j.foodchem.2010.10.063. Jurenka, J. S. (2009). Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research. Alternative Medicine Review. Jyothi, N. V. N., Prasanna, P. M., Sakarkar, S. N., Prabha, K. S., Ramaiah, P. S., & Srawan, G. Y. (2010). Microencapsulation techniques, factors influencing encapsulation efficiency. Journal of Microencapsulation, 27(3), 187–197. http://dx.doi.org/ 10.3109/02652040903131301. Karunaratne, D. N., Siriwardhana, D. A. S., Ariyarathna, I. R., Rajakaruna, R. M. P. I., Banu, F. T., & Karunaratne, V. (2016). Nutrient delivery through nanoencapsulation. Nutrient Delivery. Elsevier653–680. http://doi.org/10.1016/ B978-0-12-804304-2.00017-2. Kulkarni, S., Dhir, A., & Akula, K. K. (2009). Potentials of curcumin as an antidepressant. The Scientific World Journal, 9, 1233–1241. http://dx.doi.org/ 10.1100/tsw.2009.137. Leitner, A., Walzthoeni, T., Kahraman, A., Herzog, F., Rinner, O., Beck, M., & Aebersold, R. (2010). Probing native protein structures by chemical cross-linking, mass spectrometry, and bioinformatics. Molecular & Cellular Proteomics: MCP, 9(8), 1634–1649. http://dx.doi.org/10.1074/mcp.R000001-MCP201. Martínez-Ruvalcaba, A., Sánchez-Díaz, J. C., Becerra, F., Cruz-Barba, L. E., & GonzálezÁlvarez, A. (2009). Swelling characterization and drug delivery kinetics of polyacrylamide-co-itaconic acid/chitosan hydrogels. Express Polymer Letters, 3 (1), 25–32. http://dx.doi.org/10.3144/expresspolymlett.2009.5. Mukerjee, A., & Vishwanatha, J. K. (2009). Formulation, characterization and evaluation of curcumin-loaded PLGA nanospheres for cancer therapy. Anticancer Research, 29(10), 3867–3875 http://doi.org/29/10/3867[pii]. Murawala, P., Tirmale, A., Shiras, A., & Prasad, B. L. V. (2014). In situ synthesized BSA capped gold nanoparticles: Effective carrier of anticancer drug Methotrexate to MCF-7 breast cancer cells. Materials Science and Engineering: C, 34, 158–167. http://dx.doi.org/10.1016/j.msec.2013.09.004. Mythri, R. B., Jagatha, B., Pradhan, N., Andersen, J., & Bharath, M. M. S. (2007). Mitochondrial complex I inhibition in Parkinson’s disease: how can curcumin protect mitochondria? Antioxidants & redox signaling 9(3), 399–408. http://dx. doi.org/10.1089/ars.2007.9.ft-25. Park, T. G. (1995). Degradation of poly(lactic-co-glycolic acid) microspheres: Effect of copolymer composition. Biomaterials, 16(15), 1123–1130. http://dx.doi.org/ 10.1016/0142-9612(95)93575-X. Puvvada, N., Rajput, S., Kumar, B. N. P., Sarkar, S., Konar, S., Brunt, K. R., . . . Pathak, A. (2015). Novel ZnO hollow-nanocarriers containing paclitaxel targeting folatereceptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression. Scientific Reports, 5, 11760. http://dx.doi. org/10.1038/srep11760. Revathy, S., Elumalai, S., Benny, M., & Antony, B. (2011). Isolation, purification and identification of curcuminoids from turmeric (Curcuma longa l .) by column chromatography. Journal of Experimental Sciences, 2(7), 21–25 Retrieved from jexpsciences.com/article/download/7767/3965. Sánchez-Vioque, R., Clemente, A., Vioque, J., Bautista, J., & Millán, F. (1999). Protein isolates from chickpea (Cicer arietinum L.): Chemical composition, functional properties and protein characterization. Food Chemistry, 64(2), 237–243. http:// dx.doi.org/10.1016/S0308-8146(98)00133-2. Sharma, R. A., Gescher, A. J., & Steward, W. P. (2005). Curcumin: The story so far. European Journal of Cancer. http://dx.doi.org/10.1016/j.ejca.2005.05.009. Shrishail, D., Handral, H. K., Handral, R., Tulsianand, G., & Shruthi, S. D. (2013). Turmeric: Nature’s precious medicine. Asian Journal of Pharmaceutical and Clinical Research, 6(3), 10–16. Singh, S. P., Wahajuddin, & Jain, G. K. (2010). Determination of curcumin in rat plasma by liquid–liquid extraction using LC-MS/MS with electrospray ionization: Assay development, validation and application to a pharmacokinetic study. Journal of Bioanalysis & Biomedicine, 02(04), 079–084. http://dx.doi.org/ 10.4172/1948-593x.1000027. Solanki, H. K., Pawar, D. D., Shah, D. A., Prajapati, V. D., Jani, G. K., Mulla, A. M., & Thakar, P. M. (2013). Development of microencapsulation delivery system for long-term preservation of probiotics as biotherapeutics agent. BioMed Research International, 2013, 1–21. http://dx.doi.org/10.1155/2013/620719. Subirade, M., Remondetto, G., & Beaulieu, L. (2003). Whey protein-derived biomaterials and their use as bioencapsulation and delivery systems. Hemijska Industrija, 57(12), 617–621. http://dx.doi.org/10.2298/HEMIND0312617S.

86

I.R. Ariyarathna, D.N. Karunaratne / Food Packaging and Shelf Life 10 (2016) 79–86

Tang, C.-H., & Li, X.-R. (2013). Microencapsulation properties of soy protein isolate: Influence of preheating and/or blending with lactose. Journal of Food Engineering, 117(3), 281–290. http://dx.doi.org/10.1016/j.jfoodeng.2013.03.018. Tayyem, R. F., Heath, D. D., Al-Delaimy, W. K., & Rock, C. L. (2006). Curcumin content of turmeric and curry powders. Nutrition and Cancer, 55(2), 126–131. http://dx. doi.org/10.1207/s15327914nc5502_2. Thakam, A., & Saewan, N. (2014). Stability of emulsion containing curcumin Zn (II) and Mg (II) complexes. H&PC Today, 9(1), 44–48 Retrieved from http://www. teknoscienze.com/Articles/HPC-Today-Stability-of-emulsion-containingcurcumin-Zn-II-and-Mg-II-.aspx#.U5zwp3JdWe4. Tsai, Y. M., Chien, C. F., Lin, L. C., & Tsai, T. H. (2011). Curcumin and its nanoformulation: The kinetics of tissue distribution and blood-brain barrier penetration. International Journal of Pharmaceutics, 416(1), 331–338. http://dx. doi.org/10.1016/j.ijpharm.2011.06.030.

Wang, Y.-J., Pan, M.-H., Cheng, A.-L., Lin, L.-I., Ho, Y.-S., Hsieh, C.-Y., & Lin, J.-K. (1997). Stability of curcumin in buffer solutions and characterization of its degradation products. Journal of Pharmaceutical and Biomedical Analysis, 15(12), 1867–1876. http://dx.doi.org/10.1016/S0731-7085(96)02024-9. Weinbreck, F., Minor, M., & de Kruif, C. G. (2004). Microencapsulation of oils using whey protein/gum Arabic coacervates. Journal of Microencapsulation, 21(6), 667–679. http://dx.doi.org/10.1080/02652040400008499. Zebib, B., Mouloungui, Z., & Noirot, V. (2010). Stabilization of curcumin by complexation with divalent cations in glycerol/water system. Bioinorganic Chemistry and Applications, 2010, . http://dx.doi.org/10.1155/2010/292760 []. van der Spiegel, M., Noordam, M. Y., & van der Fels-Klerx, H. J. (2013). Safety of novel protein sources (insects, microalgae, seaweed, duckweed, and rapeseed) and legislative aspects for their application in food and feed production. Comprehensive Reviews in Food Science and Food Safety, 12(6), 662–678. http:// dx.doi.org/10.1111/1541-4337.12032.