Fabrication and characterization of curcumin loaded ovalbumin nanocarriers and bioactive properties

Abstract

In this study, curcumin loaded ovalbumin nanoparticles (CONPs) were fabricated at optimized processing conditions and compared with the neat ONPs. The particles were characterized for molecular, thermal, antimicrobial, and antioxidant properties. The particle size values varied from 45.64 nm to 138.14 nm and the encapsulation efficiency of the CONP was 24%. SEM images indicated that ONPs and CONPs had spherical shapes and the particle diameters and size distributions were in accordance with the DLS measurement results. Fabrication of CONPs provided better (P < 0.05) inhibition on test pathogens as compared to pure curcumin, which demonstrates that particle size reduction of curcumin positively influenced its antibacterial efficiency. It was also clear that nanoencapsulation of curcumin significantly (P < 0.05) increased its antioxidant activity, suggesting that the curcumin/ovalbumin nanoencapsules could achieve similar antioxidant effect at much lower curcumin concentrations. FTIR results showed that curcumin was entrapped inside the ovalbumin nanocarriers successfully. According to DSC measurements, the melting temperature of ovalbumin did not change by curcumin encapsulation. In conclusion, the results suggested that ONPs could be an available carrier for encapsulation of curcumin at nano scale and had the potential to be used in the food industry and other bioactive delivery systems.

Keywords:
bioactive delivery systems; nanotechnology; food science and technology

1 Introduction

The use of plants in the remedy of diseases dates back to almost the beginning of humankind since their beneficial effects have been known by ancient times. As a consequence of the traditional medicinal use of plants, they have drawn great attention in modern pharmacology and medicine in a couple of decades. Turmeric (Curcuma longa L.), possessing curcuminoid bioactive compounds in the rhizome has also been widely used for the treatment of inflammatory diseases (Abu-Taweel et al., 2020; Ammon & Wahl, 1991; Maheshwari et al., 2006). Curcumin (diferuloylmethane) – (1,7-bis (4-hydroxy-3-methoxyphenyl)-1,6-hepadiene-3,5-dione) is the major phenolic compound of turmeric rhizomes, which gives their characteristic yellow color (Anderson et al., 2000). Extensive research on curcumin has indicated that it had numerous health-promoting effects such as antimicrobial, antioxidant, anti-carcinogen and anti-inflammatory activitiy at in vivo and in vitro conditions (Ak & Gülçin, 2008; De et al., 2009; López-Lázaro, 2008; Menon & Sudheer, 2007). Curcumin can show protection against inflammatory illnesses, neurological illnesses, cardiovascular disorders, lung disease, metabolic illnesses, liver diseases, and malignancies (Zahedipour et al., 2020). Patel et al. (2020) reviewed several studies examining the effect of cellular and molecular mechanisms of curcumin on the protection and treatment of many diseases. Curcumin can be given alone or in combination with other substances to boost their bioavailability or to provide the controlled absorption in the body. Piperine, for example, inhibits hepatic glucurconidation. When used together, it prevents curcumin from being converted to the glucurconide metabolite, allowing more medication to reach the systemic circulation (Hasanzadeh et al., 2020).

Nanotechnology has offered numerous promising applications to the food and pharmaceutical fields. Encapsulation of nutraceutical and bioactive compounds in nano-scale has drawn great attention in recent years (Rao & Naidu, 2016). It has been also well-known that nanoencapsulation improves several properties such as water solubility, biocompatibility, bioavailability, stability, bioactivity, and target specificity of phytochemicals (Wang et al., 2014). Although several in vitro beneficial properties of curcumin have been revealed, its pure form has a low in vivo bioavailability and bioabsorption in the body (Wahlström & Blennow, 1978). Salehi et al. (2019) reported that despite operating as a robust acid-base and boron indicator, the biggest challenge with curcumin when harnessing its biological activity is its bioavailability due to poor solubility, poor absorption in plasma and tissues, fast metabolism, and excretion. Nanoencapsulation of curcumin has been reported as a good way for overcoming these problems especially poor solubility and low bioavailability (Bhawana et al., 2011). Several wall materials such as chitosan, casein, bovine serum albumin, whey protein, polyurethane, polyurea, and cyclodextrin have been used for nanoencapsulation of curcumin for bioactive and medicinal purposes (Das et al., 2010; Jayaprakasha et al., 2016; Kumar et al., 2016; Lian et al., 2014; Pan et al., 2013; Souguir et al., 2013). Also, several encapsulation methods such as low or high energy emulsification, phase inversion, desolvation, electrospraying and liposome technology have been applied for curcumin (Jiang et al., 2020). Ovalbumin is known as a phospho-glycoprotein containing 385 amino acids with a 47.000 Da of molecular weight and isoelectric point (pI) of 4.8. It has several advantages such as being high abundancy and low cost to be used in encapsulation studies for food and pharmaceutical applications (Elzoghby et al., 2012; Wongsasulak et al., 2010). In this study, it was aimed to determine the optimum conditions for encapsulation of curcumin using desolvation (precipitation) method in ovalbumin based carriers.

2 Materials and methods

2.1 Materials

In this study, ovalbumin was provided from Sigma-Aldrich (product code: A5503, lyophilized powder, ≥98%, Germany) and was used as a carrier polymer in the nanoencapsulation system. Curcumin (C₂₁H₂₀O₆, M.W: 368.38) and phosphate-buffered saline (pH: 7.4, at 25 °C) were obtained from Sigma-Aldrich (Germany). Absolute ethanol was purchased from Merck (Germany).

2.2 Optimization of ovalbumin nanoparticle production parameters

In this research, different parameters including ovalbumin concentration, solution stirring rate and antisolvent/porotein concentration were selected for the optimization of nanoparticle fabrication. The points used in the optimization were selected as following: ovalbumin concentration; 10, 20, and 30 mg/mL; stirring rate; 400, 800, and 1200 rpm, and antisolvent/protein ratio; 5, 12.5, and 20 v/v. Optimization of the parameters was conducted based on the reduction of the particle size values of the resulting nanoparticles.

2.3 Preparation of ovalbumin nanoparticles

ONPs and CONPs were prepared according to a modified desolvation method described by Jahanban-Esfahlan et al. (2016). Briefly, ovalbumin was dissolved in ultra-pure water at 4 °C and the solution was added dropwise into pure ethanol (%99.5 v/v) as antisolvent under magnetic stirring at 400, 800 or 1200 rpm for 20 min. For the curcumin loaded ovalbumin nanocarriers, the ovalbumin solution was added dropwise to 100 µg/mL amount of curcumin dissolved in pure ethanol at the same conditions which were used for ONPs. The freshly prepared nanocarriers were used to determine particle size and zeta potential measurements. For further assays, the samples were freeze-dried and stored at -18 °C.

2.4 Particle size and zeta potential measurements

Particle size and zeta potential measurements of the resulting nanoparticles were performed by Nano ZSP (Malvern Instruments Corp., Worcestershire, U.K.). The samples were dispersed in pure ethanol (%99.5 v/v) and were placed into a disposable folded capillary cell having electrodes. An average of 30 measurements were run for each sample. All the measurements were performed in a cell placed in a temperature-controlled holder (25 °C).

2.5 Encapsulation efficiency

Curcumin encapsulation efficiency of the nanoparticles was determined according to the method of Brahatheeswaran et al. (2012). The supernatant was obtained from nanoparticle dispersions in PBS by centrifugation at 15.000 × g for 15 min and then the residual curcumin amount in the supernatant was evaluated by measuring the absorbance at 425 nm using a UV-vis spectrophotometer (Agilent 8453 E, Agilent Technologies, Mississauga, ON, Canada). The amount of curcumin encapsulated and the percent encapsulation (%) in the nanoparticles was calculated using the following Equations 1 and 2, respectively:

$Curcumi{n}_{encapsulated}=Curcumi{n}_{total}-Curcumi{n}_{filtrate}$ (1)

$\%Encapsulation=\frac{Curcumi{n}_{encapsulated}}{Curcumi{n}_{total}}\times 100$ (2)

2.6 Antibacterial activity

Antibacterial activity of ONPs and CONPs produced at optimum conditions was assessed by the agar diffusion method as described by Bakirdere et al. (2015) using Escherichia coli O157:H7 ATCC 33150, Salmonella enterica subsp. enterica serovar Typhimurium ATCC 14028, Staphylococcus aureus ATCC 25923, and Listeria monocytogenes ATCC 19118 as test bacteria. Firstly, the cryopreserved bacterial strains were twice activated (10⁵–10⁶ cfu/mL) using Nutrient Broth (Merck, Germany) by incubation at 37 °C for 24 h. The pour-plating method was used in the case of the agar diffusion test. Firstly, the strains were inoculated to Nutrient Agar mediums (Merck, Germany at the ratio of 1% (v:v). Following transferring the inoculated mediums into plastic petri plates aseptically, they were kept at 4 °C for 1 h for solidification. The nanoparticle solutions and pure curcumin (1 mg/mL prepared with 80% of ethanol) were pipetted into the four equidistant wells (5 mm in diameter) on the agars. Ethanol (80% v:v) was used as a control. The petri plates inoculated with the bacteria were incubated at 37 °C for 24 h. At the end of the incubation period, all plates were examined for the diameters of clear zones around the wells.

2.7 Antioxidant activity

Antioxidant activity of ONPs and CONPs was determined using DPPH (2, 2 diphenyl-1-picryl hydrazyl) radical scavenging method as described by Brand-Williams et al. (1995). The results were expressed as Trolox equivalent antioxidant capacity (TEAC) values i.e. μM of Trolox equivalent/mg of curcumin.

The copper reducing antioxidant capacity (CUPRAC) measurement was conducted according to the method given by Apak et al. (2008) with some modifications. For this aim, 1 mg of the nanoparticle was dissolved in 1 mL 80% ethanol solution. Then, 0.1 mL of the solution was mixed with 1 mL of CuCl₂ (10 mM), 1 mL neocuproine (7.5 mM) and 1 mL NH₄Ac (1 M), and then 1 mL distilled water was added to this mixture to complete the volume of the mixture to 4.1 mL. The mixture was incubated for 60 min at room temperature in the dark. Then the absorbance was measured at 450 nm using the UV-vis spectrophotometer (Agilent 8453 E, Agilent Technologies, Mississauga, ON, Canada). Antioxidant capacity was expressed as mg Trolox equivalent per g dry weight (dry base).

2.8 Scanning electron microscopy (SEM)

Scanning electron microscope (SEM, LEO 440-Zeiss; LEO Electron Microscopy Ltd., Oberkochen, Germany) at 20.000 and 10.000 × magnifications were used to determine morphological properties of the lyophilized ovalbumin-based nanoparticles. All samples were covered with a gold layer before analysis.

2.9 Fourier Transform Infrared Spectroscopy (FTIR)

The spectra of ONPs and CONPs were obtained using an ATR-FTIR (Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy) to determine their molecular structure. A Bruker Tensor 27 spectrometer (Bremen-Germany) equipped with a KBr beam splitter, a DLaTGS detector, and an ATR accessory with a diamond ATR cell was used for the characterization. The ATR-FTIR spectra of the samples were recorded from 4000 to 600 cm⁻¹ with a resolution of 2 cm⁻¹, accumulating 16 scans per spectra.

2.10 Differential scanning calorimetry (DSC)

A differential scanning calorimeter (Q100, TA Instruments Inc., New Castle, DE, USA) was used to characterize the thermal properties of the samples. For each analysis, 5 mg of sample was weighed into an aluminum pan and sealed with a hermetic lid. The samples were heated from 20 to 300 °C at a heating rate of 10 °C/min. A hermetically sealed empty aluminum pan was considered as a reference. The analyses were performed under nitrogen atmosphere, at a flow rate of 20 mL/min.

2.11 Statistical analysis

In this study, the analyses were carried out in triplicate. Statistical analysis (analysis of variance, ANOVA) was performed using a Windows-based statistical analysis software (SAS 8.2, SAS Institute, Cary, North Carolina, USA). The significance of the differences between the mean data was assessed using Duncan's multiple comparison test at a significance level of 95%.

3 Results and discussion

3.1 Optimization of nanoparticle production parameters

Ovalbumin based nanoparticles were prepared using different production conditions as seen in Table 1. Minimization of the particle size values of the nanoparticles was targeted in this optimization step. Table 1 shows the particle size and zeta potential values of the nanoparticles. Zeta potential and particle size measurements of the nanoparticles produced with 20 mg/mL and 30 mg/mL of ovalbumin could not be achieved due to the protein aggregation. Therefore, the concerning results were not given.

Table 1
Particle size and zeta potential values of optimized ONPs.

Ovalbumin concentration (mg/mL)	Stirring rate (rpm)	Antisolvent/ protein (mL/mL)	Particle size (nm)	Zeta potential (mV)
10	400	5.0	138.14 ± 6.52a	-4.54 ± 0.21a
10	400	12.5	74.25 ± 0.72b	-4.18 ± 0.28a
10	400	20.0	71.52 ± 1.58c	-4.67 ± 0.94a
10	800	5.0	125.54 ± 3.84d	-4.52 ± 0.26a
10	800	12.5	72.84 ± 2.42e	-4.79 ± 0.11a
10	800	20.0	69.73 ± 3.36f	-4.16 ± 0.31a
10	1200	5.0	89.22 ± 2.14g	-4.61 ± 0.54a
10	1200	12.5	47.81 ± 0.25h	-4.84 ± 0.88a
10	1200	20.0	45.64 ± 1.54i	-4.12 ± 0.11a

• Different letters in the same column indicate a significant difference (P < 0.05) between the results.

As seen in Table 1, the particle size values varied from 45.64 nm to 138.14 nm. An increase of stirring rate to 1200 rpm caused a significant (P < 0.05) decrease in the particle size while ovalbumin concentration did not make a significant influence. The results showed that mechanical agitation provided well dispersion of the nanoprticles in the solution, providing the lowering effect on particle size. On the other hand, as the antisolvent/ protein ratio was increased, smaller particles were formed. It is due to the number of polymer chains per unit volume of solvent and the influence of polymer concentration on the viscosity (Li & Kaner, 2006).

3.2 Encapsulation efficiency, particle size, and zeta potential

In this study, CONPs were fabricated at optimized processing conditions (10 mg/mL of ovalbumin, 1200 rpm of stirring rate, and 20 mL/mL of antisolvent/protein ratio) and compared with the neat ONPs produced at the same conditions. The encapsulation efficiency of the CONP was 24%.

Particle size and zeta potential values of the optimized CONPs and ONPs were given in Table 2. Each sample was dispersed in pure ethanol (%99.5 v/v) and sonicated for 2 min before analysis and all the measurements were performed at 25 °C.

Table 2
Particle size and zeta potential values of the ovalbumin nanoparticles produced at optimized conditions.

Sample	Particle Size (nm)	Zeta Potential (mV)
ONPs	45.64 ± 1.54b	-4.12 ± 0.11b
CONPs	89.47 ± 0.58a	-0.35 ± 0.24a

• ONPs: Ovalbumin nanoparticles, CONPs: Curcumin loaded ovalbumin nanoparticles. Different letters in the same column indicate a significant difference (P < 0.05) between the results.

Curcumin loading to ovalbumin nanoparticles caused significant increase in particle size (P < 0.05). Electrokinetic potential, namely zeta potential, in colloidal systems, is defined as the stability degree of colloidal dispersions and indicates the interaction between positive or negative charged particles (Xiong et al., 2016). The Zeta potential of ONPs was determined as -4.12 and curcumin loading into the ONPs brought the zeta potential value close to zero. The alteration of the zeta potential by the curcumin loading gives idea about an electrostatic interaction between curcumin and ovalbumin. In a study conducted by Niu et al. (2021), similar interaction was determined between nanoparticles prepared with ovalbumin and sodium carboxymethylcellulose complex. In another research in which curcumin loaded PLA (polylactic acid) nanoparticles were fabricated, the presence of curcumin in the nanoparticles reduced the negative zeta potential value from -36.18 mV to -1.12 mV (Rachmawati et al., 2016).

3.3 Antimicrobial activity

The antimicrobial activity of pure curcumin, ONPs, and CONPs was given in Table 3. ONPs did not show antibacterial activity against any strains. It was seen that fabrication of CONPs provided better (P > 0.05) inhibition on the test bacteria as compared to pure curcumin. This demonstrates that particle size reduction of curcumin positively influenced its antibacterial efficiency. Susceptibility of Gram-positive test bacteria, namely L. monocytogenes and S. aureus against CONPs was higher than Gram-negatives (S. Typhimurium and E. coli O157:H7). This could be owing to differences in the composition and structure of respective cell membranes. As known, Gram-positive bacteria have an outer peptidoglycan layer while Gram-negative bacteria have an outer phospholipidic membrane, which can cause curcumin to interact in different ways when it comes into contact with them (Bhawana et al., 2011). These results were in accordance with the study of Bhawana et al. (2011) who reported that the activity of nanocurcumin was more pronounced against S. aureus and Bacillus subtilis than E. coli and Pseudomonas aeruginosa.

Table 3
Antimicrobial activity of the ovalbumin nanoparticles produced at optimized conditions.

Sample	Inhibition zone (mm)
	Escherichia coli O157:H7	Salmonella Typhimurium	Staphylococcus aureus	Listeria monocytogenes
Curcumin	7.67 ± 0.29cB	11.33 ± 0.58bB	9.83 ± 0.29bB	14.17 ± 1.04aB
ONPs	0.00 ± 0.00aC	0.00 ± 0.00aC	0.00 ± 0.00aC	0.00 ± 0.00aC
CONPs	10.17 ± 0.29cA	12.67 ± 0.29bA	13.33 ± 0.29bA	17.17 ± 0.29aA

• ONPs: Ovalbumin nanoparticles, CONPs: Curcumin loaded ovalbumin nanoparticles. Different letters in the same column indicate a significant difference (P < 0.05) between the results. The same uppercase letters within the same column show that the results are not statistically significantly different (P > 0.05)

Curcumin has been known for its antimicrobial activity for long times (Moghadamtousi et al., 2014). Therefore, it has been used in encapsulation studies for food and clinical applications in order to increase its activity and obtain controlled release. Several studies have also been conducted to determine its mode of antibacterial action. It was reported that curcumin showed its antibacterial activity against E. coli and Bacillus subtilis by inhibiting the FtsZ polymerization and disruption of prokaryotic cell division (Kaur et al., 2010). Inhibitory activity of curcumin against Helicobacter pylori was ensued by deactivation of metalloproteinase-3 and metalloproteinase-9 enzymes which plays as an inflammatory role in mice and cultured cell infections (Kundu et al., 2011).

3.4 Antioxidant activity

Antioxidant activity of the curcumin-ovalbumin nanoparticles was measured by DPPH and CUPRAC assays and the results were presented in Table 4. DPPH is a very stable free radical with nitrogen present at its center. Its stability mainly originates from the spatial barrier of resonance stabilization of the three benzene rings, so that the unpaired electrons on the nitrogen atoms sandwiched in the middle cannot play the role of the necessary electron pair (Mohammadian et al., 2019). Antioxidant activity of ONP was negligible. This may be resulted from the OVA protein containing thiol, which contains some aromatic amino acid residues or amino acids such as tryptophan, tyrosine, and methionine and acts as hydrogen donors to be oxidized (Liu et al., 2017). On the other hand, nanoencapsulation of curcumin significantly (P < 0.05) increased the antioxidant activity of curcumin, suggesting that the curcumin nanoencapsulation system prepared with ovalbumin could exhibit a synergistic effect. It might be said that OVA facilitated the conjugate structure of curcumin to provide the proton to DPPH and improved the free radical scavenging ability of curcumin (Liang et al., 2015; Xie et al., 2019). Similar effects were also observed in CUPRAC analysis results.

Table 4
Antioxidant activity of the ovalbumin nanoparticles produced at optimized conditions as stated by DPPH and CUPRAC radical scavenging values.

Sample	DPPH (µM TE /mg sample)	CUPRAC (mg TE/mg sample)
Curcumin	28.21 ± 1.68b	46.60 ± 0.86b
ONPs	1.28 ± 0.04c	1.12 ± 0.06c
CONPs	43.21 ± 0.87a	62.95 ± 4.14a

• ONPs: Ovalbumin nanoparticles, CONPs: Curcumin loaded ovalbumin nanoparticles. Different letters in the same column indicate a significant difference (P < 0.05) between the results.

In a study conducted by Niu et al. (2021), it was found that fabrication of curcumin loaded ovalbumin/sodium carboxymethylcellulose nanoparticles enhanced solubility and bioavailability of curcumin compared to its pure form. In another research, antioxidant activity was improved by forming ovalbumin-curcumin complex (Liu et al., 2017). Moreover, Xie et al. (2019) found that curcumin loaded ovalbumin/carragenan complex nanoparticles improved the thermal stability, light stability, and antioxidant activity of curcumin. Although it is difficult to clearly explain the enhancement of the antioxidant capacity of curcumin by protein encapsulation, based on the literature, it can be said that curcumin and ovalbumin could form complexes by binding, and this effect may lead to a secondary structure change of the ovalbumin protein, which becomes more prone to pyrolysis (Liu et al., 2017).

3.5 SEM

SEM micrographs of CONPs and ONPs were given in Figure 1. As indicated in Table 3, particle size was determined as 45.64 nm and 89.47 nm for ONPs and CONPs, respectively. According to SEM results, the particle diameters and size distributions were in accorfance with the DLS measurements. Although loading the particles with curcumin increased the particle size, it did not cause a change in its morphological structure. SEM micrographs confirmed that both of ONPs and CONPs were spherical in shape. Dried ONPs and CONPs samples were also shown to retain their physical shape and stability during the lyophilization process.

Figure 1
SEM micrographs of curcumin loaded (CONPs) and unloaded (ONP) ovalbumin nanoparticles.

3.6 FTIR

FTIR spectroscopy measurement was done in order to make molecular characterization ONPs and CONPs, as the results were presented in Figure 2. The peaks observed at 2962 and 2932 cm^-1 were assigned to stretching vibrations of C-H binding. The FTIR spectra of CONPs and ONPs showed that there was not a significant polymer-curcumin interaction, which was understood from the similarity of the peaks at major vibration points.

Figure 2
FTIR graphics of curcumin loaded (CONP) and unloaded (ONP) ovalbumin nanoparticles.

The results also revealed that curcumin was successfully entrapped inside the ovalbumin nanocarriers, which was demonstrated by the lack of additional peaks for CONPs. These results were in accordance with the findings of Jithan et al. (2011) and Thadakapally et al. (2016). However, small vibrations at 879, 967, 1124, 1280, 2050, and 2341 cm^-1 wavelengths which were absent in the FTIR profile of ONP, indicated the limited molecular interaction between curcumin. On the other hand, the band intensity of CONPs was always higher than that of ONP, showing that curcumin incorporation increased the energy of the bindings between the molecules of albumin.

3.7 DSC

DSC profiles of the nanoparticles were presented in Figure 3. A broad endothermic peak was observed at both nanoparticle samples near 105 °C, showing that the melting temperatures did not change by curcumin encapsulation. It was also seen that curcumin entrapment increased the melting enthalpy of the ONP from 154.8 J/g to 174.1 J/g, as measured by the peak areas. The characteristic endothermic peak of protein appeared at 231 °C in both DSC profiles of the samples. However, the enthalpy was reduced with the encapsulation of curcumin in the protein shell, which indicates that protein structure organization was partially lost by the encapsulation process. A similar finding was also reported by Luppi et al. (2011), who found that the characteristic endothermic peak of the bovine serum albumin protein (BSA) samples was determined at 231 °C for both of them, but the enthalpy values were different.

Figure 3
DSC profiles of curcumin loaded (C-ONP) and unloaded (ONP) ovalbumin nanoparticles.

4 Conclusion

In the present study, it was indicated that ONPs were well matrix to carry curcumin and increase its bioactive properties. Curcumin loaded ONPs provided better antimicrobial activity than pure curcumin. Also, the antioxidant activity of curcumin was significantly increased by the nanoencapsulation process. It was noted that the spherical shapes of the nanoparticles were obtained by the desolvation method and protected during the lyophilization. On the other hand, the encapsulation process had no negative effect on the thermal, molecular, and bioactive properties of curcumin and ovalbumin. In conclusion, ovalbumin was confirmed as a good carrier of curcumin, and ovalbumin based nanoparticles could be conveniently used to deliver bioactive components in the food industry.

Acknowledgements

This study was supported by the Scientific Research Projects Coordination Department of Yildiz Technical University, Turkey with the Project code of 2015-07-05-KAP02.

• Practical Application: Curcumin is an excellent bioactive material with several health benefits. However, its low water solubility limits its efficient use in the food industry. In the present study, ovalbumin nanoparticles (ONPs) and curcumin loaded ovalbumin nanoparticles (CONPs) were successfully fabricated and characterized in terms of structural and bioactive properties. The results showed that the encapsulation process enhanced bioactive properties of curcumin and ONPs was a good carrier for low solubility substances such as curcumin and applications in the bioactive delivery systems.

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Publication Dates

• Publication in this collection
  25 Mar 2022
• Date of issue
  2022

History

• Received
  14 June 2021
• Accepted
  30 Nov 2021