Abstract
Curcumin (CCM) is a natural polyphenol with promising pharmacological potential. This potential is severely restricted, however, due to its limited bioavailability, poor solubility and stability. To address this, several systems of curcumin and polyethylene glycol, PEG (PEG4000 or PEG6000), were synthetized, with or without whey protein concentrate (WPC), trans-resveratrol (RES) or silymarin (SIL) using solid dispersion technique. Firstly, CCM-PEG composites were synthesized using PEG4000 or PEG6000 for 1:8 mol ratio by polymer melting method. Further, the CCM-WPC-PEG4000 composite for 1:0.4:8 mol ratio and CCM-WPC-PEG6000 composite for 1:0.5:10 mol ratio were synthesized. Furthermore, CCM-RES-WPC-PEG and CCM-SIL-WPC-PEG composites were prepared for 1:2.5:0.4:10 mol ratio for PEG4000 or PEG6000. The composite formation was investigated by Fourier transform infrared spectroscopy (FTIR). The thermal stability of synthesized composites was analyzed through thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) revealing a high stability up to 200 °C. Thus, each composite formulation was optimized to carry CCM, RES and WPC or CCM, SIL and WPC within PEG matrix primarily by hydrogen bonds and van der Waals interactions. This study demonstrated that all synthesized composites may have potential advantages for applications such as nutraceuticals, functional foods, supplements and pharmaceuticals.
Introduction
Many plants have a specific biological and pharmacological activity that can be successfully exploited for the design of new and better drugs [1, 2], nutraceuticals and nanostructured functional foods [3, 4]. A natural antioxidant and anti-inflammatory aid, turmeric (Curcuma longa), has been used for millennia for different remedies in Asian traditional medicine. This has been linked to its higher content in curcuminoids (3–7% mass) when compared to other members of Curcuma spp. These curcuminoids are mainly comprised of curcumin, demethoxycurcumin and bisdemethoxycurcumin, alongside 14 terpene-conjugated ones [5, 6].
However, due to their chemical structure, curcuminoids have a limited solubility in water, which, in turn, minimizes their pharmacological potential. The curcumin molecule is highly hydrophobic and cannot be used systemically because of its poor oral bioavailability caused by its limited water solubility and dissolution properties [1,2,3, 7]. Instability at physiological pH, rapid metabolism and fast elimination of CCM is also quite restricting in terms of bioavailability.
Literature presents various methods used to increase the solubility and bioavailability of poorly soluble drugs, such as solid dispersions [2], or inclusion in β-cyclodextrin [8, 9].
Polyethylene glycol (PEG) is used to both decrease degradation and increase solubility of drugs in pharmacological applications. The composite formation of polyethylene glycol with different bioactive molecules, such as proteins or drugs [10], can help the obtained nanoparticles to circulate more within blood, as PEG might help the immune system and process that marks old cells and pathogens for elimination (opsonization) [11, 12]. PEG is also used as an excipient in many pharmaceutical products and used to “camouflage” drug molecules to enhance their circulation time in blood system and evade premature elimination by immune system. There is abundant research in regard to improving the solubility and bioavailability of curcumin through the use of PEG [13,14,15,16].
Among biopolymers, proteins also stand out due to their biodegradability and high ability to bind drug molecules [17]. These amphiphilic molecules can form composites (molecular associations) with curcumin (hydrophobic in nature) through a self-assembly mechanism, with the hydrophobic part at the interior, and the exterior hydrophilic part forming a micellar structure, increasing the aqueous solubility of curcumin [18]. There are quite a few studies regarding curcumin and whey protein both in its concentrate (WPC) [19,20,21,22,23,24] and isolate forms (WPI) [19, 25,26,27,28,29,30,31,32] as well as different protein fractions found in whey, such as β-lactoglobulin [19, 33,34,35], α-lactalbumin [19], bovine serum albumin (BSA) [36, 37] or lactoferrin [38]. Curcumin was also studied in regard to other types of proteins, both animal–human serum albumin and holo-transferrin [39], β-casein [40] as well as vegetable such as pea [32, 41,42,43], soy [44,45,46,47,48,49], rice [50], zein [41, 42, 51,52,53,54], walnut [55], or sunflower [56].
In the present work, we have studied a series of composites based on curcumin and PEG4000 or PEG6000, without or with addition of a protein, like whey protein concentrate (WPC), and a flavonoid polyphenol in the form of either trans-resveratrol (RES) or silymarin (SIL). These flavonoids were selected due to their reported synergistic effect when combined with curcumin, namely trans-resveratrol [57, 58] and silymarin [59].
Both PEG and WPC are used as stabilizing agents, increasing curcumin’s bioavailability. Accordingly, we hypothesized that using CCM in the presence of both PEG and whey protein will benefit the formation of stable composites of CCM. Moreover, taking into account the reported synergistic effect between CCM and RES as well as CCM and SIL, we assumed that using them together in the presence of PEG and whey protein will assist the realization of stable multi-component composites as delivery systems of these biomolecules with therapeutic potential or as food ingredients for human health benefits.
This investigation focuses on the synthesis and characterization of the prepared composites in binary (PEG-CCM), ternary (PEG-CCM-WPC) and quaternary (PEG-CCM-RES-WPC or PEG-CCM-SIL-WPC) systems through Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The major objective was to evaluate the thermal properties of all composites in comparison with their precursors and appraise their thermal stability for functional nutraceuticals for potential dietary medicine applications.
The composites were prepared by using solid dispersion technique [2] and PEG melting method [60]. The binary (PEG-CCM) composites were synthesized at a selected curcumin: polymer (1:8) mole ratio, using PEG4000 or PEG6000. The novelty of this study is related especially to the effects of CCM binding on WPC within PEG matrix. Further, the effects of CCM interaction with flavonoid molecules in the presence of WPC within PEG matrix were discussed.
Materials and methods
Materials
Curcumin (95% purity) was obtained from Sigma-Aldrich (Darmstadt, Germany). Trans-resveratrol (99% purity) was purchased from Sigma-Aldrich (Saint Louis, USA). Silymarin (80.6% purity) was purchased from Nanjing Hua Cheng Pharmaceuticals (Liaoning, China) with a content of natural phenolics as follows: silybin 40.93%, isosilybin 11.65%, silychristin 17.08%, and silydianin 4.51%. Whey protein concentrate (80% protein) was purchased from Foodcom S.A. (Warsaw, Poland). PEG4000 and PEG6000 were acquired from Merck (Darmstadt, Germany). The KBr, FTIR grade of high purity, was purchased from Merck (Darmstadt, Germany).
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Enhanced stability of curcumin and polyethylene glycol composites in the presence of flavonoids and whey protein concentrate synthesis, structural evaluation and thermal analysis
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Tomoaia-Cotisel, M., Kun, AZ., Rácz, CP. et al. Enhanced stability of curcumin and polyethylene glycol composites in the presence of flavonoids and whey protein concentrate: synthesis, structural evaluation and thermal analysis. J Therm Anal Calorim (2025).
https://doi.org/10.1007/s10973-025-14111-0
