Elif Özyılmaz1, Özge Çağlar1,2, Sebahat Aşcıoğlu1, Merve Bezgin1, Mukaddes Saklan1, Handan Sağlam1, Oytun Erbaş3

1Department of Biochemistry, Selçuk University, Faculty of Science, Konya, Turkey
2Department of Chemistry, Selçuk University, Faculty of Science, Konya, Turkey
3Department of Physiology, Demiroğlu Science University, Faculty of Medicine, Istanbul, Turkey

Keywords: Curcumin, iron oxide nanoparticles, magnetic nanoparticles, turmeric.

Abstract

Objectives: In this study, it was aimed to obtain curcumin from the extracts of the turmeric plant by using a simple and fast magnetic separation method, unlike other standard methods.

Materials and methods: Magnetic iron oxide nanoparticles (IONPs) were prepared by chemical co-precipitation of Fe3+ and Fe2+ ions. Magnetic nanoparticles were used to extract curcumin from turmeric. In addition, curcumin was characterized and compared with commercial curcumin. Curcumin was recovered by purifying it from extracts of the turmeric plant.

Results: Fe3O4 nanoparticles were characterized using transmission electron microscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy, and Ultraviolet (UV)-visible spectra. Transmission electron microscopy analysis was used to describe the particle size and surface morphology of Fe3O4 nanoparticles, and the XRD device was used to explain X-ray diffraction. Curcumin was extracted from turmeric plant extracts purified with Fe3O4 nanoparticles. Fourier-transform infrared spectroscopy was used to determine the functional groups in the structure of turmeric, Fe3O4 nanoparticles, Fe3O4 turmeric complex, commercial curcumin, and curcumin. The UV spectrum of commercial curcumin and curcumin was also examined using the Shimadzu UV-1700 Pharma spectrophotometer. It has been established that it is recovered with a purification yield of 1.5 percent following purification.

Conclusion: These results suggest that curcumin, which has research potential in the field of health, may also be beneficial in terms of creating different scientific and economic expansions and producing new studies.

Introduction

Turmeric is a perennial and tuberous herbaceous plant that belongs to the ginger family, with yellow flowers and large leaves. It is also called turmeric, saffron root, yellow dye, castor, and saffron. It is widely grown in China, India and Southeast Asia.[1] Turmeric has an important place in Indian medicine since it is used especially in cold, cough, sinusitis, rheumatic diseases, cardiovascular diseases, and skin diseases.[2-4] Curcumin substance is obtained from the turmeric plant.[5-7] It is known to have many pharmacological activities such as antioxidant, anti-inflammatory, anti-aging, analgesic, antiprotease activity, anticancer.[5,8-10] Curcumin is an antioxidant that suppresses lipid peroxidation and reduces the formation of inflammatory compounds by scavenging reactive oxygen species.[11,12] Curcumin has the ability to prevent protein accumulation that causes diseases such as Alzheimer’s and Parkinson’s diseases.[10,13,14]

Isolation of biomolecules is generally carried out using different electrophoretic, chromatographic, ultrafiltration or precipitation and solvent extraction methods.[15] All of these methods present considerable disadvantages when used on an industrial scale, such as expensive instrumentations, time-consuming processes, or large amounts of organic solvent waste.[16] Methods such as thin-layer chromatography,[17-19] high-performance liquid chromatography,[20-24] electrochemical method, [25,26] spectrofluorometry[27-29] and Ultraviolet-visible (UV-Vis) spectrophotometry[10,24,30-33] have been utilized to determine curcumin in a diversity of matrices like Curcuma longa, foodstuffs, and biological materials.

With the rapid advancement of nanotechnology, interest in magnetic nanoparticles is increasing day by day. Recently, magnetic nanoparticles have been prepared in various ways, such as sol-gel self-propagation,[34] chemical co-precipitation,[35-37] and in the tiny pools of the water-in-oil microemulsion.[38]

The prepared magnetic nanoparticles have been widely used in bionanotechnology such as magnetic resonance imaging, bioseparation, diagnostic agents, tumor hyperthermia and biomolecule immobilization.[39-51] These magnetic nanoparticles have attracted the attention of researchers with their small size, low toxicity, superparamagnetism and most importantly their specific applications.[36,51-55] In this study, curcumin, which is the miracle of nature, was obtained by purifying it quickly and easily with magnetic iron oxide nanoparticles (IONPs) without the use of expensive instruments.

Patients and Methods

Materials

Curcumin was supplied from Alfa aesar. Iron(II)chloride tetrahydrate (FeCl2.4H2O), and iron(III)chloride hexahydrate (FeCl3.6H2O), were supplied from Merck. Turmeric and all other chemicals used were obtained from various commercial sources.

Characterization

Transmission electron microscopy (TEM) was used to examine the particle size and surface morphology of Fe3O4 nanoparticles. X-ray diffraction (XRD) of the nanoparticles was determined with the Bruker™ D8 Advance device (Bruker BioSciences Espanola, S.A. Madrid, Spain). Fourier transform infrared spectroscopy (FTIR) was used to determine the functional groups in the structure of turmeric, Fe3O4 nanoparticles, Fe3O4 turmeric complex, commercial curcumin, and curcumin. The UV spectrum of commercial curcumin and curcumin was measured using the Shimadzu UV-1700 Pharma spectrophotometer (UV-1700 Pharma Spec, Shimadzu, Kyoto, Japan).

Synthesis of Fe3O4 nanoparticles

Magnetic Fe3O4 nanoparticles have been prepared by the co-precipitation method according to previous literature.[54] 50 mL 1.0 M FeCl2.4H2O and 1.75 M FeCl3.6H2O solutions were prepared with deionized water in two different beakers. Then this solution transferred to a 250 mL three-necked flask and stirred under a nitrogen atmosphere. It was observed that the color of the solution turned dark brown immediately after addition. This color indicated that IONPs were formed.

The resulting solution was heated to 80°C for 1 hour. The precipitates were isolated from the solvent by magnetic filtration and washed several times with deionized water until neutral pH. They were dried under vacuum at 50°C for 10 hours.

Curcumin extraction using magnetic nanoparticles

0.5 g Fe3O4 nanoparticles and 1 g turmeric were mixed in the sonicator in a 1:1 ethanol/ water mixture for 6 hours. Then magnetic nanoparticles were separated from the Fe3O4- curcumin composite by magnetic decantation. The resulting composite structure was dried, and ethanol and water were added in a ratio of 1:1 and remixed in the sonicator for 1 hour. The mixture was adjusted to pH 5-6. Magnetic nanoparticles were separated from the curcumin mixture by magnetic separation with a permanent magnet. The insoluble curcumin mixture was separated and the soluble part was evaporated in the evaporator and dried in a vacuum oven at 50°C.

Results

Fe3O4 nanoparticles were obtained according to the co-precipitation method of Fe2+ and Fe3+ ions.[54]

Transmission electron microscopy analysis was performed to see the particle size and morphology of synthesized Fe3O4 nanoparticles (Figure 1a). The dense aggregates were exhibited due to the lack of any repulsive force between Fe3O4 nanoparticles.

Figure 1b shows XRD patterns of synthesized Fe3O4 nanoparticles. The characteristic peaks of the Fe3O4 crystal were seen at 2θ = 30.3°, 35.5°, 43.0°, 53.0°, 57.4°, and 63.5°, respectively.

The properties of the Fe3O4 nanoparticles surface, due to the presence of under-coordinated iron (Fe) (III) sites, confer high specificity to select iron-chelating molecules from complex matrices.[17] Presenting a keto-enol functionality, curcumin tended to bind very well towards the surface of the magnetic nanoparticles. It showed that curcumin is a good ligand for the surface of Fe3O4 nanoparticles. This confirms the literature that curcumin has an important ability to form stable complexes with Fe (III).[16,56] Figure 2 shows the structure of the Fe3O4-turmeric complex.

The FTIR spectrum of the turmeric, Fe3O4, and Fe3O4-turmeric complexes, respectively, was given in Figure 3. The FTIR bands at low wavenumbers (<700 cm-1) come from vibrations from the Fe-O bonds. The FTIR bands around 604 and 534 cm-1 belong to the stretching vibration mode of Fe-O bonds in magnetite nanoparticles. It was observed that the stretching vibration modes of the turmeric, C-O bands, C=O bands, and C=C bands were at 994 cm-1, 1511 cm-1, and 1626 cm-1, respectively. The formation of the Fe3O4-turmeric was assigned by the disappearance of the characteristic band at about 994 cm-1 and the appearance of a C=C at 1624 cm-1.

Characterization of curcumin and commercial curcumin

Fourier-transform infrared spectra of curcumin obtained with commercial curcumin were compared. The FTIR spectrum of commercial curcumin of O-H, C-H, C=O and C=C bands were observed at 3508 cm-1, 1626 cm-1, 1506 cm-1, 1426 cm-1, 1203 cm-1, 1024 cm-1, respectively. Similarly, the isolated curcumin bands were observed at 3271 cm-1, 1600 cm-1, 1508 cm-1, 1203 cm-1 1024 cm-1, respectively (Figure 4).

The UV spectrum of commercial curcumin and curcumin was measured. The strong interaction between IONPs attached to the surface and phenolics in the compounds was demonstrated by UV-Vis spectrophotometry. The absorption spectrum of commercial curcumin and curcumin showed a maximum wide band at approximately 423 nm in Figure 5.[16,55-58]

Many researchers have studied the amount of curcumin in turmeric. Priyadarsini[59] reported that turmeric contains 2-9% curcuminoids, depending on the origin and the soil conditions in which it was grown. Lal reported that it is found in different amounts according to the production regions in India. It has reported that it is found at a rate of 2% in Madras and 4-7% in Alleppey.[60] In another study, Paultre et al.[61] explained that the amount of curcumin is 3-10%. From the standard curcumin calibration graph, the curcumin concentration was found to be 0.0275 mM at 423 nm. The amount of curcumin was calculated as 15 mg by using the concentration. Curcumin was recovered from the extracts of the turmeric plant by magnetic purification with an amount of 1.5%.

Discussion

There is a need for alternative treatment methods in the treatment of cancer and many diseases. The therapeutic uses of medicinal plants have attracted considerable attention in recent years.

Curcumin is a natural flavonoid. It has many important properties such as anticancer, antioxidant, and antibacterial effects. Different techniques such as chromatographic, electrophoretic are used to isolate biomolecules. These methods are both time-consuming and expensive. Therefore, simpler and more economical techniques are needed for isolation.

Magnetic Fe3O4 nanoparticles, with their low toxicity, biocompatibility, and easy separation with the help of magnets, have attracted a lot of attention in recent years, especially in applications such as targeted drug therapy, cancer therapy, enzyme immobilization, hyperthermia, and magnetic resonance imaging. Biocatalytic applications are also used in different fields such as biomedicine, biomedical, and bioengineering. A suitable magnetic field is created by adding biomolecules or organic substances to these magnetic nanoparticles, and the separation of substances can be performed quickly and easily by using magnets.[42,51]

For the isolation of curcumin, unlike other purification techniques, the use of magnetic nanoparticles was preferred considering the advantage of a simple and fast separation technique with the help of magnets. In the study, Fe3O4 nanoparticles were synthesized and their structure was confirmed by characterization techniques.[37,55,56,59,63-68]

In Figure 1a, the morphology and particle size of Fe3O4 nanoparticles was examined by TEM analysis. The formation of nanoparticles was confirmed.[5,62,63] In addition, characteristic peaks of the synthesized Fe3O4 crystals were analyzed (Figure 1b). These peaks were seen by XRD analysis at 2θ = 30.3°, 35.5°, 43.0°, 53.0°, 57.4° and 63.5°, respectively.[37,56-58,62] Turmeric, Fe3O4, and Fe3O4-turmeric compound FTIR spectra were also studied (Figure 3). The stretching vibrations of Fe3O4, Fe-O bonds, the stretching vibrations of in the turmeric structure C-O bands, C=O bands, and C=C bands were confirmed.[37,58,61-64] Curcumin was obtained from the extracts of the turmeric plant by using the obtained nanoparticles. It was determined that curcumin from the extracts of the turmeric plant was recovered with a purification efficiency of 1.5%.

The FTIR and UV spectra of commercial curcumin and curcumin were examined and compared. Figure 5 showed a significant interaction between surface-bound IONPs and phenolics in the compounds. The absorption spectra of both commercial curcumin and obtained curcumin showed a broad band maximum at 423 nm.[16,59,65]

It is thought that this study can be beneficial in terms of the fact that curcumin, which has the potential to research in the field of health, can create different expansions both scientifically and economically and produce new studies.

In conclusion, Fe3O4 magnetic nanoparticles were synthesized and used to obtain curcumin from turmeric. The synthesized Fe3O4 magnetic nanoparticles were characterized by FTIR, XRD and TEM. The resulting curcumin compound was purified quickly and easily in the presence of magnetic IONPs without using expensive devices. Then, it was compared to commercial curcumin. Curcumin from extracts of the turmeric plant was recovered with a purification yield of 1.5%. With this method, it is predicted that biomolecules that can be easily transported from the laboratory to the industrial level can be easily purified by using an economical and environmentally friendly method, without the need for expensive devices.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This study was supported with the application number 1919B011902144 within the scope of Scientific and Technological Research Council of Turkey (TUBITAK)/BIDEB/2209-A University Students Research Projects Support Program.

Acknowledgments

We would like to thank TUBITAK and Selcuk University for their support.

References

  1. Arlı M, Çelik H. The biological importance of curcumin. EAJS 2020;6:21-34.
  2. Chumroenphat T, Somboonwatthanakul I, Saensouk S, Siriamornpun S. Changes in curcuminoids and chemical components of turmeric (Curcuma longa L.) under freeze-drying and low-temperature drying methods. Food Chem 2021;339:128121.
  3. Ammon HP, Anazodo MI, Safayhi H, Dhawan BN, Srimal RC. Curcumin: A potent inhibitor of leukotriene B4 formation in rat peritoneal polymorphonuclear neutrophils (PMNL). Planta Med 1992;58:226.
  4. Miquel J, Bernd A, Sempere JM, Díaz-Alperi J, Ramírez A. The curcuma antioxidants: Pharmacological effects and prospects for future clinical use. A review. Arch Gerontol Geriatr 2002;34:37-46.
  5. Peng S, Li Z, Zou L, Liu W, Liu C, McClements DJ. Enhancement of curcumin bioavailability by encapsulation in sophorolipid-coated nanoparticles: An in vitro and in vivo study. J Agric Food Chem 2018;66:1488-97.
  6. Basol N, Savas AY, Meral A, Erbas O. The valuable effects of potent antioxidant curcumin in cisplatin induced liver and kidney injury. Cumhuriyet Med J 2018;40:9-18.
  7. Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: Problems and promises. Mol Pharm 2007;4:807-18.
  8. Meng R, Wu Z, Xie QT, Cheng JS, Zhang B. Preparation and characterization of zein/ carboxymethyl dextrin nanoparticles to encapsulate curcumin: Physicochemical stability, antioxidant activity and controlled release properties. Food Chem 2021;340:127893.
  9. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: The indian solid gold. In: Aggarwal, BB, Surh, YJ, Shishodia, S, editors. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease. New York; Springer Publications; 2007. p. 1-76.
  10. Anand P, Thomas SG, Kunnumakkara AB, Sundaram C, Harikumar KB, Sung B, et al. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature. Biochem Pharmacol 2008;76:1590-611.
  11. Pérez-Garrido A, Helguera AM, Ruiz JM, Rentero PZ. Topological sub-structural molecular design approach: Radical scavenging activity. Eur J Med Chem 2012;49:86-94.
  12. Wang YJ, Pan MH, Cheng AL, Lin LI, Ho YS, Hsieh CY, et al. Stability of curcumin in buffer solutions and characterization of its degradation products. J Pharm Biomed Anal 1997;15:1867-76.
  13. Yan JW, Li YP, Ye WJ, Chen SB, Hou JQ, Tan JH, et al. Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation. Bioorg Med Chem 2012;20:2527-34.
  14. Masuda M, Suzuki N, Taniguchi S, Oikawa T, Nonaka T, Iwatsubo T, et al. Small molecule inhibitors of alpha-synuclein filament assembly. Biochemistry 2006;45:6085-94.
  15. Kitts DD, Weiler K. Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr Pharm Des 2003;9:1309-23.
  16. Magro M, Campos R, Baratella D, Ferreira MI, Bonaiuto E, Corraducci V, et al. Magnetic purification of curcumin from Curcuma longa rhizome by novel naked maghemite nanoparticles. J Agric Food Chem 2015;63:912-20.
  17. Horák D, Babic M, Macková H, Benes MJ. Preparation and properties of magnetic nano- and microsized particles for biological and environmental separations. J Sep Sci 2007;30:1751-72.
  18. Safarik I, Safarikova M. Magnetic techniques for the isolation and purification of proteins and peptides. Biomagn Res Technol 2004;2:7.
  19. Lyon JL, Fleming DA, Stone MB, Schiffer P, Williams ME. Synthesis of Fe oxide Core/Au shell nanoparticles by iterative hydroxylamine seeding. Nano Letters 2004;4:719-23.
  20. Zhang Y, Kohler N, Zhang M. Surface modification of superparamagnetic magnetite nanoparticles and their intracellular uptake. Biomaterials 2002;23:1553-61.
  21. Lu Y, Yin Y, Mayers BT, Xia Y. Modifying the surface properties of superparamagnetic iron oxide nanoparticles through a sol-gel approach. Nano Letters 2002;2:183-6.
  22. Urbanova V, Magro M, Gedanken A, Baratella D, Vianello F, Zboril R. Nanocrystalline iron oxides, composites, and related materials as a platform for electrochemical, magnetic, and chemical biosensors. Chem Mater 2014;26:6653-73.
  23. Mackay ME, Tuteja A, Duxbury PM, Hawker CJ, Van Horn B, Guan Z, et al. General strategies for nanoparticle dispersion. Science 2006;311:1740-3.
  24. Magro M, Faralli A, Baratella D, Bertipaglia I, Giannetti S, Salviulo G, et al. Avidin functionalized maghemite nanoparticles and their application for recombinant human biotinyl-SERCA purification. Langmuir 2012;28:15392-401.
  25. Magro M, Sinigaglia G, Nodari L, Tucek J, Polakova K, Marusak Z, et al. Charge binding of rhodamine derivative to OH- stabilized nanomaghemite: Universal nanocarrier for construction of magnetofluorescent biosensors. Acta Biomater 2012;8:2068-76.
  26. Sinigaglia G, Magro M, Miotto G, Cardillo S, Agostinelli E, Zboril R, et al. Catalytically active bovine serum amine oxidase bound to fluorescent and magnetically drivable nanoparticles. Int J Nanomedicine 2012;7:2249-59.
  27. Magro M, Valle G, Russo U, Nodari L, Vianello F. Maghemite Nanoparticles and Method for Preparing Thereof. 2012; World Patent WO/2012/010200.
  28. Venerando R, Miotto G, Magro M, Dallan M, Baratella D, Bonaiuto E, et al. Magnetic nanoparticles with covalently bound self-assembled protein corona for advanced biomedical applications. J Phys Chem C 2013;117:20320-31.
  29. Magro M, Campos R, Baratella D, Lima G, Holà K, Divoky C, et al. A magnetically drivable nanovehicle for curcumin with antioxidant capacity and MRI relaxation properties. Chemistry 2014;20:11913-20.
  30. Nagpal M, Sood S. Role of curcumin in systemic and oral health: An overview. J Nat Sci Biol Med 2013;4:3-7.
  31. Liu D, Chen Z. The effect of curcumin on breast cancer cells. J Breast Cancer 2013;16:133-7.
  32. Yallapu MM, Jaggi M, Chauhan SC. beta-Cyclodextrincurcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces 2010;79:113-25.
  33. Maheshwari RK, Singh AK, Gaddipati J, Srimal RC. Multiple biological activities of curcumin: A short review. Life Sci 2006;78:2081-7.
  34. Yang X, li Q, Zhao J, Li B, Wang Y. ChemInform abstract: Preparation and magnetic properties of controllable-morphologies Nano-SrFe 12 O 19 particles prepared by sol-gel self-propagation synthesis. Journal of Alloys and Compounds 2009;475:312-5.
  35. Wang X, Zhao C, Zhao P, Dou P, Ding Y, Xu P. Gellan gel beads containing magnetic nanoparticles: An effective biosorbent for the removal of heavy metals from aqueous system. Bioresour Technol 2009;100:2301-4.
  36. Wu Y, Wang Y, Luo G, Dai Y. In situ preparation of magnetic Fe3O4-chitosan nanoparticles for lipase immobilization by cross-linking and oxidation in aqueous solution. Bioresour Technol 2009;100:3459-64.
  37. Ozyilmaz E, Ascioglu S, Yilmaz M. Calix[4]arene tetracarboxylic acid-treated lipase immobilized onto metal-organic framework: Biocatalyst for ester hydrolysis and kinetic resolution. Int J Biol Macromol 2021;175:79-86.
  38. Wang Y, Wang X, Luo G, Dai Y. Adsorption of bovin serum albumin (BSA) onto the magnetic chitosan nanoparticles prepared by a microemulsion system. Bioresour Technol 2008;99:3881-4.
  39. Sayin S, Yilmaz E, Yilmaz M. Improvement of catalytic properties of Candida rugosa lipase by sol-gel encapsulation in the presence of magnetic calix[4]arene nanoparticles. Org Biomol Chem 2011;9:4021-4.
  40. Yilmaz E. Enantioselective enzymatic hydrolysis of racemic drugs by encapsulation in sol-gel magnetic sporopollenin. Bioprocess Biosyst Eng 2012;35:493-502.
  41. Gupta AK, Gupta M. Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials 2005;26:3995-4021.
  42. Ozyilmaz E, Alhiali A, Caglar O, Yilmaz M. Preparation of regenerable magnetic nanoparticles for cellulase immobilization: Improvement of enzymatic activity and stability. Biotechnol Prog 2021;37:e3145.
  43. Krízová J, Spanová A, Rittich B, Horák D. Magnetic hydrophilic methacrylate-based polymer microspheres for genomic DNA isolation. J Chromatogr A 2005;1064:247-53.
  44. Ito A, Shinkai M, Honda H, Kobayashi T. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 2005;100:1-11.
  45. Mornet S, Vasseur S, Grasset F, Veverka P, Goglio G, Demourgues A, et al. Magnetic nanoparticle design for medical applications. Progress in Solid State Chemistry 2006;34:237-47.
  46. Neuberger T, Schöpf B, Hofmann H, Hofmann M, von Rechenberg B. Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system. Journal of Magnetism and Magnetic Materials 2005;293:483-96.
  47. del Campo A, Sen T, Lellouche JP, Bruce IJ. Multifunctional magnetite and silica- magnetite nanoparticles: Synthesis, surface activation and applications in life sciences. Journal of Magnetism and Magnetic Materials 2005;293:33-40.
  48. Saiyed ZM, Sharma S, Godawat R, Telang SD, Ramchand CN. Activity and stability of alkaline phosphatase (ALP) immobilized onto magnetic nanoparticles (Fe3O4). J Biotechnol 2007;131:240-4.
  49. Yilmaz E, Sezgin M, Yilmaz M. Immobilized copper-ion affinity adsorbent based on a crosslinked b-cyclodextrin polymer for adsorption of Candida rugosa lipase. Biocatal Biotransform 2009;27:360-6.
  50. Yildiz H, Ozyilmaz E, Bhatti AA, Yilmaz M. Enantioselective resolution of racemic flurbiprofen methyl ester by lipase encapsulated mercapto calix[4] arenes capped Fe3O4 nanoparticles. Bioprocess Biosyst Eng 2017;40:1189-1196.
  51. Ozyilmaz E, Sayin S. A magnetically separable biocatalyst for resolution of racemic naproxen methyl ester. Bioprocess Biosyst Eng 2013;36:1803-6.
  52. Chen F, Luo GS, Wang YJ. Studies on adsorption properties of chemically modified chitosan resins to diuretics. Acta Polymerica Sinica 2005:53-9.
  53. Caglar O, Ozyilmaz E, Erbas O. Superparamagnetic iron oxide nanoparticles use in the temporal lobe epilepsy model. D J Tx Sci 2021;6:66-72.
  54. Yilmaz E, Sezgin M, Yilmaz M. Immobilization of Candida rugosa lipase on magnetic sol-gel composite supports for enzymatic resolution of (R,S)-Naproxen methyl ester. Journal of Molecular Catalysis B: Enzymatic 2011;69:35-41.
  55. Saikia C, Das MK, Ramteke A, Maji TK. Effect of crosslinker on drug delivery properties of curcumin loaded starch coated iron oxide nanoparticles. Int J Biol Macromol 2016;93:1121-32.
  56. Borsari M, Ferrari E, Grandi R, Saladini M. Curcuminoids as potential new iron-chelating agents: spectroscopic, polarographic and potentiometric study on their Fe(III) complexing ability. Inorganica Chimica Acta 2002;328:61-8.
  57. Ozyilmaz E, Sayin S, Arslan M, Yilmaz M. Improving catalytic hydrolysis reaction efficiency of sol-gelencapsulated Candida rugosa lipase with magnetic b-cyclodextrin nanoparticles. Colloids Surf B Biointerfaces 2014;113:182-9.
  58. Hiremath CG, Heggnnavar GB, Kariduraganavar MY, Hiremath MB. Co-delivery of paclitaxel and curcumin to foliate positive cancer cells using Pluronic-coated iron oxide nanoparticles. Prog Biomater 2019;8:155-168.
  59. Priyadarsini KI. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014;19:20091-112.
  60. Lal J. Turmeric, curcumin and our life: A review. Bulletin of Environment Pharmacology and Life Sciences 2012;1:11-7.
  61. Paultre K, Cade W, Hernandez D, Reynolds J, Greif D, Best TM. Therapeutic effects of turmeric or curcumin extract on pain and function for individuals with knee osteoarthritis: A systematic review. BMJ Open Sport Exerc Med 2021;7:e000935.
  62. González-Martínez E, Pérez AG, González-Martínez DA, Águila CRD, Urbina EC, Ramírez DU, et al. Chitosan-coated magnetic nanoparticles; exploring their potentialities for DNA and Cu(II) recovery. Inorganic and Nano-Metal Chemistry 2021;51:1098- 107.
  63. Pham XN , Nguyen TP , Pham TN , Tran TTN, Tran TVT. Synthesis and characterization of chitosancoated magnetite nanoparticles and their application in curcumin drug delivery. Advances in Natural Sciences: Nanoscience and Nanotechnology 2016;7:045010.
  64. Ebadi M, Bullo S, Buskara K, Hussein MZ, Fakurazi S, Pastorin G. Release of a liver anticancer drug, sorafenib from its PVA/LDH- and PEG/LDH-coated iron oxide nanoparticles for drug delivery applications. Sci Rep 2020;10:21521.
  65. Ebadi M, Saifullah B, Buskaran K, Hussein MZ, Fakurazi S. Synthesis and properties of magnetic nanotheranostics coated with polyethylene glycol/5- fluorouracil/layered double hydroxide. Int J Nanomedicine 2019;14:6661-78.
  66. Prakash N, Sadaf M, Salomi A, Daniel EC. Cytotoxicity of functionalized iron oxide nanoparticles coated with rifampicin and tetracycline hydrochloride on Escherichia coli and Staphylococcus aureus. Appl Nanosci 2019;9:1353-66.
  67. Mareeswaran PM, Babu E, Sathish V, Kim B, Woo S, Rajagopal S. p-Sulfonatocalix[4]arene as a carrier for curcumin. New Journal of Chemistry 2014;38:1336-45.
  68. Barick KC, Rathee E, Gawali SL, Sarkar A, Kunwar A, Priyadarsini KI, et al. Pluronic stabilized Fe3O4 magnetic nanoparticles for intracellular delivery of curcumin. RSC Advances 2016;6:98674-81.