Anticancer, antioxidant, and antimicrobial activities of nanoemulsions based on water-in-olive oil and loaded on biogenic silver nanoparticles

Ragaa A. Hamouda; Bayan A. Eshmawi; Amna A. Saddiq

doi:10.1515/gps-2024-0026

Article Open Access

Anticancer, antioxidant, and antimicrobial activities of nanoemulsions based on water-in-olive oil and loaded on biogenic silver nanoparticles

Ragaa A. Hamouda , Bayan A. Eshmawi and Amna A. Saddiq

Published/Copyright: June 26, 2024

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From the journal Green Processing and Synthesis Volume 13 Issue 1

Abstract

Nanoemulsions (NEMs) are more stable and permeable than regular emulsions because of their increased surface area and smaller particle sizes, which are stabilized by emulsifiers and consist of nanometer-sized droplets. Utilization of an olive oil nanoemulsion (NEM-olive oil) loaded with silver nanoparticles (Ag-NPs) derived from marine alga Turbinaria turbinata may be effective against microorganisms and cancer cell lines. NEM-olive oil was made by mixing olive oil, surfactant (Span:Tween (28:72)), and D water (1:4:5). The marine alga Turbinaria turbinata was used for the synthesis of Ag-NPs (Tu-Ag-NPs), and combined with NEM-olive oil (1:1) to synthesize Ag-NPs loaded in olive oil–water nanoemulsion (Ag/NEM-olive oil). Transmission electron microscopy, energy-dispersive X-ray analysis, zeta potential, Fourier transform infrared, and X-ray powder diffraction spectroscopy were used to characterize the nanoparticles. Both NEM-olive oil and Ag/NEM-olive oil nanoparticles showed a negative surface charge and small diameter. The major components of NEM-olive oil are dodecanoic acid, 2-penten-1-yl ester, 9-octadecenoic acid, and oleic acid. All tested nanoparticles exhibited anticancer activity against the CACO-2 cell line and Hep G2, and antimicrobial activities against E. faecalis, S. aureus, E. coli, and C. albicans. The present research suggested that olive oil NEM loaded with marine algae Ag-NPs can be a safe and economical anticancer, antimicrobial, and drug delivery.

Keywords: marine algae; olive oil; nanoemulsion; anticancer; antioxidant; antimicrobial

1 Introduction

Cancer is an atypical type of tissue proliferation in which cells divide erratically, resulting in a gradual increase in the number of dividing cells [1]. Cancer is a common disorder among people worldwide [2]. Despite the discovery of several chemical and natural drugs for the treatment of cancer, it is still the most dangerous disease in the world, causing mortality in many people [3]. The detection of new anticancer drugs with low-danger effects has become an essential and critical target in many studies [3,4]. A large number of essential oils have been used in many in vitro studies to influence a variety of breast cancer cells [5]. A variety of valuable components are found in olive oil, which could be useful for the inhibition or possible treatment of cancer [6].

Olive oil contains monounsaturated fatty acids, which may be accompanied by a decreased risk of some cancers, and mainly phenolic compounds that have antioxidant activities [7]. Biologically synthesized silver nanoparticles (Ag-NPs) specifically have a wide range of medicinal applications that minimize toxicity and cost and are found to be exceptionally stable [8]. It has been observed that Ag-NPs have cytotoxic effects through an increase in ROS production associated with DNA damage, apoptosis, and necrosis [9].

Many bioactive compounds can be used in the synthesis of nanoparticles, such as caffeic acid, which acts as a reducing agent for the reduction of Ag⁺ into Ag-NPs [10]. Ag-NPs can be fabricated using a mixture of glucose and CTAB in the presence of ammonia [11]. Cyanidin 3,5-di-O-glucoside extracted from the red-orange rose petals was used effectively in synthesized gold nanoparticles and displayed excellent inhibitory effect against S. aureus, E. coil, and Candida [12]

Algae play a major role in the biosynthesis of Ag-NPs with a small size range, which opens the door for using Ag-NPs as anticancer agents [13]. Ag-NPs are biogenic by the marine brown alga Padina pavonia with high stability and rapid formation with small sizes ranging from 49.58 to 86.37 nm [14]. Ag-NPs bio-fabricated by polysaccharides were extracted from brown algae and showed a spherical shape, small size, pronounced cytotoxicity toward rat glioma cells, and antibacterial activities [15]. The alginate extracted from Laminaria ochroleuca brown alga was a good reducing and stabilizing agent in the biosynthesis of Ag-NPs, which exhibited remarkable antibacterial activity against both Gram-positive and Gram-negative bacteria [16]. The Ag-NPs were fabricated using laminarin extracted from Turbinaria ornata and exhibited cytotoxicity in retinoblastoma Y79 cell lines [17]. The edible marine brown alga aqueous extract of Ecklonia cava is a useful reducing agent for the environmentally friendly synthesis of Ag-NPs with potent antioxidant, antibacterial, and anticancer properties against human cervical cancer cells [18]. The brown alga Padina tetrastromatica can be used for eco-friendly and useful biosynthesis of antimicrobial Ag-NPs against Bacillus sp. Bacillus subtilis, Klebsiella planticola, and Pseudomonas sp. [19]. Shanthi et al. [20] demonstrated the potential applications of fucoidan-coated anionic Ag-NPs derived from Turbinaria decurrens in medicines. The Ag-NPs biosynthesized by the brown alga Sargassum wightii have good enzyme inhibitory, antioxidant, and antibacterial effects [21]. Ag-NPs synthesized by olive oil exhibited maximum antibacterial activity against Klebsiella pneumonia and Ag-NPs biosynthesized by olive oil could be used as a safe natural consequence against multidrug-resistant bacteria [22]. Ag-NPs loaded in the tea tree oil nanoemulsion (TTO NEM) were an efficient antimicrobial agent for the management of infections and multidrug-resistant bacteria (MDRB) [23]. Green synthesized Ag-NPs loaded in various herbal oils (oil-in-water nanoemulsion technique) showed anticancer activity against MCF-7 human breast cancer, and these nanoparticles have been established in various biomedical treatments such as cosmetics [24]. Chitosan-capped silver sols (Chit/Ag-NPs) exhibited higher antimicrobial activities against Staphylococcus aureus and Candida albicans than those with pure chitosan [25].

This is a new study on the synthesis of olive oil water nanoemulsion, and it is loaded in Ag-NPs green synthesis by brown marine alga Turbinaria turbinata, characterizations, and the evaluation of the effects of olive oil water nanoemulsion, and its loaded in green synthesis Ag-NPs as anticancer, antioxidant, and antibacterial activities.

2 Materials and methods

2.1 Materials

The marine alga Turbinaria turbinata was collected from Jeddah Beach, Saudi Arabia (KSA), cleaned, washed with tap water, followed by DD water, and dried in the shade, followed by grinding and drying in an electrical oven at 60°C, until a constant weight was obtained. Pure olive oil was purchased from Jeddah, Saudi Arabia (KSA). All chemicals used were of analytical grade and were purchased from Sigma-Aldrich Company.

2.2 Algal extract

One gram of air-dried T. turbinata was blended with 100 mL of deionized (DD) water, boiled for 1 h, and then cooled and filtered.

2.3 Biosynthesis of Tu-Ag-NPs

About 0.17 g of AgNO₃ was mixed with 90 mL of DD water, and 10 mL of the algal extract was added dropwise using a magnetic stirrer at 60°C, until the color changed to dark brown [26].

2.4 Nanoemulsion synthesis

A mixture of Span 80 and Tween 80 (28:72) was chosen as the surfactant and mixed thoroughly under magnetic stirring. Approximately 4 ml of the surfactant was added to 1 g of olive oil, mixed well, and then 5 mL of water was added dropwise under magnetic stirring for 15 min.

2.5 Nanoemulsion loaded in Tu-Ag-NPs

Subsequently, Tu-Ag-NPs (2 mg·mL⁻¹) were mixed with the previously synthesized nanoemulsion under magnetic stirring [23].

2.6 Nanoparticle characterization

2.6.1 UV spectrophotometry

Spectroscopic methods were used to analyze the nanoparticles and nanoparticles loaded with bioactive compounds [27,28]. UV-Vis spectroscopy (ATI Unicam 5625 UV/VIS Vision Software V3.20) was used to determine the surface plasmon absorption (SPR) of the biogenic Tu-Ag-NPs

2.6.2 Fourier transform infrared (FTIR) spectroscopy

Nanoemulsion and Tu-Ag-NP-loaded nanoemulsion were characterized by FTIR spectroscopy) using an FT-IR 5300 spectrophotometer (JASCO Europe S.r.l, Cremella, Italy), in the range between 400 and 4,000 cm⁻¹

2.6.3 X-ray powder diffraction (XRD)

The crystalline or amorphous nanoemulsion and Tu-Ag-NP-loaded nanoemulsion were characterized using an X-ray diffractometer (PAN Analytical X-Pert PRO, Spectris plc, Almelo, The Netherlands).

2.6.4 Zeta potential analysis

Zeta potential analysis afforded the details of the stabilization of nanoemulsion, and Tu-Ag-NP-loaded nanoemulsion was analyzed using a Malvern Zeta size Nano-Zs90 (Malvern, Westborough, PA, USA).

2.6.5 Energy-dispersive spectroscopy (EDS)

The surface morphology and elemental contents of nanoemulsions and Tu-Ag-NP-loaded nanoemulsions were examined using a field emission scanning electron microscope (SEM) equipped with energy-dispersive spectroscope (JEOL JSM-6510/v, Tokyo, Japan).

2.6.6 Transmission electron microscopy (TEM)

The particle sizes and shapes of the nanoemulsion and Tu-Ag-NP-loaded nanoemulsion were determined using TEM (JEOL JSM-6510/v, Tokyo, Japan).

2.6.7 GC-MS analysis of the nanoemulsion

The chemical composition of the nanoemulsion was determined using a Trace GC1310-ISQ mass spectrometer (Thermo Scientific, Austin, TX, USA) at the Regional Center for Mycology and Biotechnology at Al-Azhar University. The column used was TG–5MS (30 m × 0.25 mm × 0.25 µm film thickness), with the initial and final temperatures being 35–280°C, which was increased by 3°C·min⁻¹ to 200°C. Helium was used as a carrier, and the volume of the injected sample was 1 µL. The ion source temperature was set to 200°C. The compounds were recognized by the WILEY 09 and NIST 11 mass spectral databases.

2.7 Free radical scavenging activity (DPPH)

Approximately 1 ml of different concentrations (20, 40, 80, 160, and 200 µg·mL⁻¹) of each Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil was added to the DPPH solution (4 ml, 0.004% methanolic solution). After 30 min of incubation at room temperature, the absorbance of the mixture was measured at 517 nm [29]

The percentage inhibition = [ Abs ( control ) – Abs ( sample ) /Abs control ] × 100

2.8 Cell culture

RPMI-1640 was used to maintain the CACO-2 cell line in a human colon cancer patient. Both cell lines were grown in the cell culture unit at the Center for Drug Discovery Research and Development at the College of Pharmacy, Ain Shams University. Human liver cancer (Hep G2) was maintained in DMEM-high glucose. In a humidified atmosphere with 5% (v/v) CO₂ at 37°C, both media were supplemented with 10% heat-inactivated fetal bovine serum, 100 units/mL penicillin, and 100 µg·mL⁻¹ streptomycin.

2.9 Cytotoxicity assay

The test substance (dissolved in DMSO) was maintained at a stock concentration of 1,000,000 µg·mL⁻¹. The cells were seeded in 96-well plates at a density of 2, 000 cells/well. For 72 hours, the cells were subjected to various treatments, and five distinct nanoemulsions containing varying quantities of Tu-Ag-NPs were investigated. Following drug exposure, cytotoxicity was evaluated using the SRB assay as previously described [30]. Absorbance was measured at 545 nm using a microplate reader (BioTek Instruments, Vermont, USA). The relative absorbance percentage of the control was used to express the results. The experiments were conducted in triplicate. The concentration at which 50% growth inhibition was achieved, known as the half-maximal inhibitory concentration (IC50), was determined using GraphPad Prism software, version 5.00 (Graph Pad Software, Inc. La Jolla, CA, USA).

2.10 Antimicrobial activities

The antimicrobial activity of the nanoparticles was established against Staphylococcus aureus ATCC 29213 Enterococcus faecalis (ATCC 29212) (Gram-positive bacteria), and also Escherichia coli ATCC 35218 (Gram-negative bacteria) and Candida albicans ATCC 76615 (fungus). The strains were obtained from the Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, KSA.

Antibacterial and antifungal properties were screened using the agar diffusion technique. Briefly, six holes (4 mm in diameter) were cut into the seeded agar plates, and Muller-Hinton agar Petri dishes (150 mm) were inoculated with various microbial strains (cfu 10⁶). To determine the lowest inhibitory concentration, 50 μL of each sample at different concentrations was added to the wells. The Petri dishes were incubated at 37°C for 48 h. Inhibitory activity was measured using the clear zone around the holes (mm). To determine the MIC, different concentrations were prepared for each formulation (2, 1, 0.5, 0.25, 0.125, 0.0625 mg·mL⁻¹) and tested against different bacterial strains and fungi.

2.11 Statistical analysis

All data were obtained in triplicate and are presented as the designed mean and standard error (mean ± SD). Statistical analysis (ANOVA and Duncan’s multiple comparison test) was performed using SPSS software (version 16.0, professional edition). The level of significance was defined as p < 0.05.

3 Results and discussion

3.1 Characterization of nanoparticles

3.1.1 UV spectroscopy

Biogenic Ag-NPs were obtained using T. turbinata brown marine alga extract; the reactions occurred after a few minutes and were indicated by a change in color to brown. T. turbinata extract was used as the reducing and stabilizing agent. The variation in color was attributed to the excitation of the SPR of biogenic Tu-Ag-NPs. The UV-Vis absorption spectrum of Tu-Ag-NPs was observed at 422 nm (Figure 1). A single peak was obtained at 428 nm for Ag-NPs biosynthesized using T. turbinata collected from the Red Sea, Safaga, Egypt [31]. The absorption spectrum of Ag-NPs synthesized using Turbinaria conoides showed peaks at 420 nm [32], 421 nm [33], and 452 nm [34], which revealed the formation of Ag-NPs (Figure 2).

Figure 1

UV-visible absorption spectra of Tu-Ag-NPs bio-fabricated using the aqueous extract of T. turbinata brown alga (T. turbinata alga was used as a reducing and stabilizing agent, and the reaction was conducted at 60°C using magnetic stirring).

Figure 2

FT-IR spectra analysis of NEM-olive oil (4 ml of surfactant: 1 g of olive oil: 1 g of olive oil mixed well with a magnetic stirrer for 15 min).

3.1.2 FTIR spectra analysis of NEM-olive oil

Figure 2 shows the ATR-FTIR spectra of NEM-olive oil. It exhibits 13 peaks: the broad peak at 3,343 cm⁻¹ was attributed to the stretching of the O–H group [35]. The weak peaks at 2,919 and 2,852 cm⁻¹ were assigned to the alkyl chains (CH₂), which agree with the results of nanoemulsion (oleic acid) [36]. The band at 1,813 cm⁻¹ represented NO [37]. The band at 1,737 cm⁻¹ indicated C═O stretching vibration for lipids [38]. The quinoid ring (C═O) was observed at 1,637 cm⁻¹, and also observed in the nanoemulsion stabilized with Tween 80 [39]. The peak at 1,462 cm⁻¹ may denote the band of C–O–H bending in the nanoemulsion [40]. The band at 1,348 cm⁻¹ indicated NO₂ [41]. The C–N stretching of amine was observed at 1,245 cm⁻¹ [42], and the band at 948 cm⁻¹ was assigned to the C–C group [43]. The peak at 581 cm⁻¹ with other peaks, such as those at 3,418, 1,646, 1,383, and 1,121 cm⁻¹, confirmed the formation of the spinel structure and oleic acid [44]. The results in Figure 3 show the ATR-FTIR spectra of the Ag/NEM-olive oil. The results denote the small differences in the peak positions about those found in NEM-olive oil without Ag-NP loading. The peak at 3,339 cm⁻¹ was assigned to the stretching of the O–H group [45], and the sharp peak at 2,917 cm⁻¹ was assigned to the –CH stretching [46]. The small peak at 2,854 cm⁻¹ indicates the deformation of membrane phospholipids [47]. The peak at 1,358 cm⁻¹ was assigned to the symmetric carboxylate stretching [48]. The peak at 1,077 cm⁻¹ was assigned to the C–O band [49]. The band at 600 cm⁻¹ was attributed to PO₄ [50].

Figure 3

FT-IR spectra analysis of Ag/NEM-olive oil and Tu-Ag-NPs mixed with the nanoemulsion (1:1) at ambient temperature.

3.1.3 X-ray diffraction

Figure 4 shows the X-ray diffraction patterns of the NEM-olive oil and Ag/NEM-olive oil. The results demonstrate that no peaks appeared in the crystalline patterns for NEM-olive oil; in contrast, when Ag-NPs were loaded in NEM-olive oil, crystalline peaks appeared at 2θ = 4.23°, 6.28°, and 8.34°, which were assigned to Miller indices 110, 111, and 200, respectively. The NEM-olive oil has an amorphous structure, and Ag nanocrystalline is loaded by an amorphous state. The XRD results and overall assessment of the carbonated hydroxyapatite nanoemulsions (CHAp) showed an amorphous state [51]. The solid nanoemulsion preconcentrate of paclitaxel (PAC) using oil is molecularly dispersed or in an amorphous state in the matrix [52]. According to XRD analysis, the crystallinity of Ketotifen fumarate (KF) loaded by nanoemulsion was reduced, which was noticed by the loss of most peaks in the nanoparticles related to the drug [53]. The results of the X-ray diffractogram indicated crystalline Carvedilol; however, the nanoemulsion Carvedilol possessed an amorphous state in which no crystalline peaks were observed [54].

$Figure 4 X-ray diffraction of NEM-olive oil (a) and Ag/NEM-olive oil (b).$

Figure 4

X-ray diffraction of NEM-olive oil (a) and Ag/NEM-olive oil (b).

3.1.4 Zeta potential analysis

Figure 5 shows the zeta potential analysis of NEM-olive oil and Ag/NEM-olive oil. The results indicate that the surface charge of NEM-olive oil has a negative charge (−19.8 mV), and the negative charge increases when Ag-NPs were loaded in NEM-olive oil to form Ag/NEM-olive oil (−35.5 mV). Repulsion among the nanoparticles and superior constancy may be due to the negative charge of the nanoparticles, and the stability of the nanoparticles is postulated by negative charges that block aggregation and agglomeration [24]. Zeta potential measurements revealed that loading Ag NPs in tree oil nanoemulsion (TTO NEM) initiates zeta potential variations from −17.75 to −29.24 mV, which possibly advances the stability of tree oil nanoemulsion [23]. Andrographolide-loaded nanoemulsions (AG-NEMs) have a negative charge [55]. The improved hyaluronic acid established nanoemulsion formula showed a zeta potential of −23.9 mV [56]. The stability of nanoemulsions differs according to the oil types that are used in the synthesis of nanoemulsions; nanoemulsion-containing lemon grass, or mandarin EO present a high stability during storage of 56 days; however, the oregano or thyme EO-pectin nanoemulsions were unstable over storage [57]. A pomegranate seed oil (PSO) nanoemulsion loaded with α-tocopherol can be used as a delivery system with good features under severe environmental conditions [58]. The citrus essential oil (CEO) nanoemulsion had good stability during 200-day storage, which is of great significance for long-term preservation in the food industry [59].

Figure 5

Zeta potential of NEM-olive oil (a) and Ag/NEM-olive oil (b). Comparison between surface charges of the nanoparticles (c).

3.1.5 TEM images

Figures 6 and 7 display the TEM images and particle distributions of NEM-olive oil and Ag/NEM-olive oil. The image shows that the morphological NEM-olive oil is polydispersive and spherical, with sizes ranging from 7 to 15 nm (Figure 7a). The most predominated size ranged from 12.6 to 13.4 nm. The images of Ag/NEM-olive oil denote the polydispersed particles, spherical in shape, with a size ranging from 3 to 10.2 nm. The TEM image of tree oil nanoemulsion (TTO NEM) and Ag nanoparticle-loaded nanoemulsion demonstrated average sizes of 17.5 and 4.5 nm with spherical [23]. The Ag-NP nanoemulsions were spherical [60]. The combination of nanosilver and nanoemulsions produced Ag/nanoemulsions with an average size ranging from 42.9 to 135.5 nm [61]. TEM image proved that Ag-NPs were adsorbed/distributed in nanoemulsions. Moghtader et al. [62] reported that Ag-NPs were adsorbed/distributed on the pure-cotton fabrics nanoemulsion.

Figure 6

TEM images of NEM-olive oil (a, b) and Ag/NEM-olive oil (c, d). The emulsion-encapsulated Ag-NPs.

Figure 7

Particle size distributions of NEM-olive oil (a) and Ag/NEM-olive oil (b).

3.1.6 Energy dispersive X-ray (EDS)

Figure 8 shows the energy dispersive X-ray (EDS) measurements and SEM images of the Ag/NEM-olive oil. Carbon, oxygen, sodium, magnesium, silicon, calcium, and silver were present at 66.93, 33.09, 0.13, 0.08, 0.01, 0.09, and 0.7 wt%, respectively. Oxygen and carbon were predominant at 33.09 and 66.93 wt%, but in the case of Ag, they were 0.7 wt%, which denotes the low amount of silver loaded in the nanoemulsion. An Ag peak was observed at 3 keV. In the energy-dispersive X-ray analysis, the peak observed at 3 keV corresponds to the binding energy of Ag Lω [63]. The peak for silver was observed at 3 keV, which is predictable for the absorption of metallic silver nanocrystalline [64].

Figure 8

SEM image (a) and the energy dispersive X-ray (EDS) measurement (b) of Ag/NEM-olive oil.

3.1.7 Phytochemical analysis

Phytochemical screening was performed to determine the presence of the most active compounds that were found in NEM-olive oil (Table 1). GC-MS analysis revealed the following major phytochemical compounds with percentages:dodecanoic acid, 2-penten-1-yl ester, 9-octadecenoic acid, prostaglandin A1-biotin, acetic acid, 2-acetoxymethyl-1,2,3-trimethylbutyl ester, oleic acid, dotriacontane, dodecanoic acid, hexadecanoic acid, 1-(1-methylethyl)-1,2-ethanediyl ester, octadecanoic acid, palmitic acid tetramethylene ester, hexadecanoic acid, 1-(1-methylethyl)-1,2-ethanediyl ester, isosorbide, tetradecanoic acid, and hexadecanoic acid at 13.35, 8.56, 6.71, 5.75, 4.97, 4.82, 4.43, 3.49, 3.04, 2.71, 2.46, 2.44, 2.21, and 2%, and there were many compounds where the percentage was <2%. All the identified compounds are classified as fatty acids except some compounds, such as isosorbide, which are classified as diols and prostaglandin A1-biotin as lipophilic. The compounds in the nanoemulsion have biological activities such as antimicrobial, anticancer, antiviral, antioxidant, and antiproliferative effects (Table 1).

Table 1

Ingredients of olive oil-nanoemulsion

Rt	Compounds	Formula	Area %	Classification	Advantages	Ref.
23.31	Isosorbide	C₆H₁₀O₄	2.44	Diols	Biomedical engineering materials	[65]
27.52	Decanoic acid	C₁₀H₂₀O₂	0.25	Saturated fatty acid	Antibacterial activity	[66]
35.89	Dodecanoic acid	C₁₂H₂₄O₂	4.43	Saturated fatty acid	Antimicrobial activity	[67]
36.04	Dodecanoic acid, ethyl ester	C₁₄H₂₈O₂	0.41	Saturated fatty acid	Antibacterial, antiviral, and antioxidant	[68]
42.64	Tetradecanoic acid	C₁₄H₂₈O₂	2.21	Saturated fatty acid	Larvicidal efficacy	[69]
43.23	Tetradecanoic acid, ethyl ester	C₁₆H₃₂O₂	0.24	Saturated fatty acid	Used in cosmetics	[70]
8.11	9-Hexadecenoic acid	C₁₆H₃₀O₂	0.45	Unsaturated fatty acid	Anti-inflammatory	[71]
48.72	Octanoic acid, oct-3-en-2-yl ester	C₁₈H₃₆O₂	1.18	Saturated fatty acid	Antimicrobial	[72]
49.08	Hexadecanoic acid	C₁₆H₃₂O₂	2.00	Unsaturated fatty acid	Anti-inflammatory	[71]
50.40	Octanoic acid, oct-3-en-2-yl ester	C₂₃H₄₆O₂	0.79	Saturated fatty acid	Antimicrobial	[72]
54.61	Oleic acid	C₁₈H₃₄O₂	4.97	Unsaturated fatty acid	Antimicrobial activity	[73]
55.42	Octadecanoic acid	C₁₈H₃₆O₂	3.04	Saturated fatty acid	Anticancer	[74]
62.81	Dodecanoic acid, 2-penten-1-yl ester	C₁₇H₃₂O₂	13.35	Saturated fatty acid	Antimicrobial activity	[75]
64.31	Acetic acid, 2-acetoxymethyl-1,2,3-trimethylbutyl ester	C₁₂H₂₂O₄	5.57	Organic acid	Antimicrobial activities	[76]
65.63	Hexadecanoic acid	C₁₉H₃₈O₄	0.87	Unsaturated fatty acid	Anti-inflammatory	[71]
68.77	Prostaglandin A1-biotin	C₃₅H₅₈N₄O₅S	6.71	lipophilic molecule	Antiproliferative effects	[77]
69.14	Octadecanoic acid	C₃₉H₇₆O₅	0.73	Saturated fatty acid	Anticancer	[74]
70.06	Dotriacontane	C₁₈H₃₀D₆O	4.82	n-alkane	Activation of human neutrophils	[78]
70.72	9-Octadecenoic acid	C₂₁H₄₀O₄	8.56	Saturated fatty acid	Antibacterial	[79]
71.2	Octadecanoic acid	C₁₉H₃₈O₄	1.18	Saturated fatty acid	Anticancer	[74]
72.64	9-Octadecenamide	C₂₂H₄₃NO	1.45	Fatty amide	Antioxidative and hypolipidemic	[80]
73.89	Dotriacontane	C₁₈H₁₆O₇	1.16	n-alkane	Activation of human neutrophils	[78]
74.04	Hexadecanoic acid, 1-(1-methylethyl)-1,2-ethanediyl ester	C₃₇H₇₂O₅	3.49	Unsaturated fatty acid	Anti-inflammatory	[71]
75.15	Hexadecanoic acid	C₃₇H₇₂O₄	1.93	Unsaturated fatty acid	Anti-inflammatory	[71]
78.83	Hexadecanoic acid, 1-(1-methylethyl)-1,2-ethanediyl ester	C₃₇H₇₂O₅	2.46	Unsaturated fatty acid	Anti-inflammatory	[71]
79.82	Hexadecanoic acid, 1-[[[(2-aminoethoxy)hydroxyphosphinyl]oxy]methyl] -1,2-ethanediyl ester	C₃₇H₇₄NO₈	1.87	Unsaturated fatty acid	Anti-inflammatory	[71]
83.25	Oleic acid, eicosyl ester	C₃₈H₇₄O₂	0.73	Unsaturated fatty acid	Antimicrobial activity	[73]
83.80	Oleic acid, eicosyl ester	C₃₈H₇₄O₂	0.65	Unsaturated fatty acid	Antimicrobial activity	[73]
92.19	Palmitic acid, tetramethylene ester	C₃₆H₇₀O₄	2.71	Saturated fatty acid	Antimicrobial activity	[81]

3.2 Antioxidant activity

The DPPH assays were used to evaluate the free-radical-scavenging potential to compare Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil (Figure 9). The results show that Tu-Ag-NPs have the highest antioxidant at low concentrations compared to those of NEM-olive oil and Ag/NEM-olive oil. However, at the highest concentrations (40–200 µg·mL⁻¹), the Ag/NEM-olive oil possessed higher antioxidant activities than Tu-Ag-NPs and NEM-olive oil. The results demonstrate the values are not significant between Tu-Ag-NPs and Ag/NEM-olive oil at 160 µg·mL⁻¹; in contrast, the values are significant between Tu-Ag-NPs and Ag/NEM-olive oil when the concentrations increased to 200 µg·mL⁻¹. The increased concentration of olive nanoemulsions was accompanied by enhanced antioxidant activity [82]. Olive oil can be used to formulate nanoemulsions. Such emulsions would be beneficial because of their greater antioxidant activity, derived from olive oil, in addition to providing a means of delivery to foods [83]. Olive oil is composed of many antioxidants to entrap the radicals such as O2˙⁻, RO˙, and OH˙. Therefore, olive oil is used to avoid autoxidation of curcumin in aqueous preparations in the form of oil-in-water nanoemulsions and is also used as an anticancer agent because of its antioxidant activities [84].

Figure 9

Antioxidant activities of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil. Bars represent error bars, and different letters denote significant values.

3.3 Anticancer activity

The cytotoxic activity of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil was examined in cancer cell lines, such as human colon cancer CACO-2 and human liver cancer (Hep G2). The results shown in Figure 10a demonstrate the inhibitory effect of Tu-Ag-NPs on human colon cancer CACO-2 and human liver cancer (Hep G2). The IC50 of Tu-Ag-NPs on human colon cancer CACO-2 and human liver cancer (Hep G2) was 2.375 and 2.214 µg·mL⁻¹, respectively. The biosynthesis of Ag-NPs by Guiera senegalensis leaf extract possessed anticancer activities against Hep G2 with IC50 (33.25 μg·mL⁻¹) [85]. An increase in Brassica Ag-NP concentrations increased the reserve of Caco-2 cells [86]. The inhibitory effect of Ag-NPs may be related to their size because of their cytotoxic effect, which is caused by their interference with cellular proteins and the induction of changes in their chemistry. Additionally, small nanoparticles in cancer cells may contribute to this effect [26].

Figure 10

(a) Effect of Tu-Ag-NPs on human colon cancer CACO-2 and human liver cancer (Hep G2). (b) Effect of NEM-olive oil on two different cancer cell lines, human colon cancer CACO-2 and human liver cancer (Hep G2). (c) Effect of Ag/NEM-olive oil on two different cancer cell lines, human colon cancer CACO-2 and human liver cancer (Hep G2).

Figure 10b shows the cytotoxic effects of different concentrations of NEM-olive oil against CACO-2 and Hep G2. The results demonstrate that all tested concentrations (0.1–1,000 µg·mL⁻¹) of NEM-olive oil possessed anticancer activities against CACO-2 and Hep G2, and the same effects were observed in two types of cancer. Eugenol (EU) and eugenol-loaded nanoemulsions (EU NEs) caused inhibition effects against both HB8065 and HTB-37, and the inhibition effect due to the ROS of EU and EU NEs triggers apoptosis [87]. Nigella sativa L. nanoemulsion reduces the viability of hepatocellular carcinoma cells and enhances ROS intensity and chromatin condensation [88]. The MTT assay revealed IC50 values of 283.3 and 227 µg·mL⁻¹ for clove essential oil and clove essential oil nanoemulsions against CACO-2 [89].

The results in Figure 10c reveal the cytotoxic effect of Ag/NEM-olive oil on cancer cell lines, CACO-2, and Hep G2. The results clearly show that Ag/NEM-olive oil caused cytotoxicity against CACO-2 and Hep G2. There was a significant difference at low concentrations of 1 µg·mL⁻¹ Ag/NEM-olive oil between cell lines CACO-2 and Hep G2. The highest concentrations (10, 100, and 1,000 µg·mL⁻¹) of Ag/NEM-olive oil exhibited the same inhibition effect against CACO-2 and Hep G2. Ag nanoparticles in oil-in-water nanoemulsion possessed anticancer activity against MCF-7 human breast cancer cells [24]. Table 2 shows the IC50 of tested nanoparticles against CACO-2 and Hep G2. The results showed that Ag/NEM-olive oil caused more anticancer activity against CACO-2 than Tu/Ag-NPs, which possessed low IC50, while the reverse results were obtained with Hep G2. The IC50 in NEM-olive oil against CACO-2 was not detected due to high activities against the cancer cell line and possessed low IC50 in the case of Hep G2 (1.36 µg·mL⁻¹).

Table 2

IC50 (µg·mL⁻¹) of Tu/Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil

Treatments	Tu/Ag-NPs	NEM-olive oil	Ag/NEM-olive oil
CACO-2	2.375 ± 0.061	ND	2.196 ± 0.54
Hep-G2	2.214 ± 0.067	1.36	2.608 ± 0.133

ND. Not detected.

3.4 Antimicrobial activities

Different concentrations (2–0.0032 mg·mL⁻¹) of Tu-Ag-NPS, NEM-olive oil, and Ag/NEM-olive oil were tested against S. aureus and E. faecalis (Gram-positive bacteria) and also E. coli (Gram-negative bacteria) and C. albicans (fungus) by measuring the inhibition zone (Table 3). The results demonstrated that Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil exerted antimicrobial activities against all tested bacteria and fungi. The MIC values differed according to the type of microorganism and nanoparticles. The MIC value of Tu-Ag-NPs and Ag/NEM-olive oil against S. aureus and E. coli was 0.0065 mg·mL⁻¹, and MIC values with NEM-olive oil were 0.025 and 0.0125 against S. aureus and E. coli, respectively. The MIC value of NEM-olive oil and Ag/NEM-olive oil was 0.0065 mg·mL⁻¹, and the MIC value of Tu-Ag-NPs against E. faecalis (ATCC 29212) was 0.025 mg·mL⁻¹. The MIC values of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil were 0.0125, 0.1, and 0.025 mg·mL⁻¹, respectively. Figure 11 and demonstrate the effect of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil against S. aureus, E. faecalis, E. coli, and C. albicans. The significant effects of the tested nanoparticles differed according to the nanoparticle type and tested microorganisms. The results demonstrated that Tu-Ag-NPs and Ag/NEM-olive oil possessed the same effect against Staphylococcus aureus ATCC 29213. There were significant differences between NEM-olive oil and Ag/NEM-olive oil against E. faecalis, but the highest effect was observed for Tu-Ag-NPs. The lowest inhibitory activities of Tu-Ag-NPS and Ag/NEM-olive oil were against Escherichia coli ATCC 35218. The highest inhibition zone of all treated microorganisms was observed with Tu-Ag-NPs against C. albicans. Nanoemulsions with a size of 7 nm were effective against MDR Staphylococcus aureus and Escherichia coli [90]. Phytosphingosine nanoemulsions (Ps-NEs) exhibit broad antimicrobial activity against bacteria and yeast [91]. These results are in agreement with Rosato et al. [92], who reported that the nanoemulsion containing Carlina acaulis L (EO-NEM) exhibited antibacterial activities against Gram (+) bacteria with MIC values ranging between 7.5 and 60 mg·mL⁻¹ mg·mL⁻¹, while lower values of MIC were obtained against Gram-negative strains. The transformation of thyme oil to a nanoemulsion improved antibacterial activity against food-borne pathogens, which damaged bacterial cell membranes after the nanoemulsion treatment [93]. The nanoemulsion formulation affected Staphylococcus aureus through changes in the cell wall composition and cell shape, reducing the respiration of the bacterial cell and promoting potassium leakage from the cell permeability to the cytoplasmic contents [94]. The transformation of olive oil to a nanoemulsion boosted its antimicrobial activity against all tested microorganisms Staphylococcus aureus, Bacillus cereus, E. coli, Salmonella typhi, and Candida albicans [82]. Chouhan et al. [95] summarized the mechanism of the effect of nanoemulsion against microorganisms through induced leakage, disruption of the cell membrane, inhibition of ergosterol biosynthesis, permeabilized membrane, and cell wall damage. The nanoemulsion droplets accumulate in the epidermis and dermis of the cells and can interact directly and disrupt organisms at the site of infection, killing pathogens by physical disruption of the cell wall and subsequent lysis of the organism [96].

Table 3

Antimicrobial activities and MIC of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil

Nanotypes	Microorganisms	0.2	0.1	0.05	0.025	0.0125	0.0065
Tu/Ag-NPs	S. aureus	14 ± 1	13.25 ± 1.2	13. ± 1.4	10.66 ± 0.75	10 ± 0	8 ± 1
	E. faecalis	11.66 ± 1.25	10 ± 1	6.16 ± 0.67	5.3 ± 0.75	0	0
	E. coli	11.66 ± 0.88	10.75 ± 0.95	10 ± 0.81	9.75 ± 0.75	9 ± 0.81	6 ± 0.81
	C. albicans	18.33 ± 0.88	16.66 ± 0.66	15.33 ± 0.33	13 ± 0.33	5.66 ± 0.33	0
NEM-olive oil	S. aureus	12 ± 0	9.25 ± 1.7	6.75 ± 0.28	5.37 ± 0.8	0	0
	E. faecalis	16.66 ± 2	12.75 ± 1.7	11.75 ± 1.15	11 ± 0.5	10.25 ± 0.5	8.75 ± 0.5
	E. coli	9 ± 1	7.25 ± 1	5.25 ± 0.28	5.12 ± 0.28	5 ± 0.28	0
	C. albicans	7.5 ± 0.0.5	6.66 ± 0.5	0	0	0	0
Ag/NEM-olive oil	S. aureus	14 ± 0.75	12.75 ± 0.95	11.25 ± 95	10 ± 0	9 ± 0	7.75 ± 0
	E. faecalis	16 ± 1	13.75 ± 0.66	12.25 ± 1.2	11.5 ± 0.66	10 ± 0.57	9 ± 0.57
	E. coli	12 ± 1	11.25 ± 0.95	10.5 ± 0.57	9.25 ± 0.95	8.25 ± 0.86	7.25 ± 1.1
	C. albicans	15.33 ± 0.88	13.66 ± 0.33	12.33 ± 0.33	6 ± 0.33	0	0

Figure 11

Antimicrobial activities of Tu-Ag-NPs, NEM-olive oil, and Ag/NEM-olive oil. Bars represent error bar, and different letters denote significant values.

Both metal/metal oxide nanocomposites and essential oils have wide-ranging spectra of bio-activities with antioxidant, anticancer, and antimicrobial activities owing to their diverse sizes, shapes, activities, physical and chemical stability, and high surface-to-volume ratios [97]. Hort et al. [98] reported no changes in biochemical, hematological, oxidative stress, and genotoxicity parameters of male Wistar rats treated with NEMs, once daily for 21 days via oral or intraperitoneal delivery. NEMs significantly improve the bioavailability and bioactivity of hydrophobic bioactives delivered orally, including nutraceuticals, vitamins, healthy fats, and medicines [99]. Oral administration of nanoemulsions loaded with pliartine enhances its solubility, bioavailability, and antitumor efficacy [100].

4 Conclusions

An olive oil nanoemulsion (NEM-Olive oil) was prepared using surfactants such as Tween and Span and homogenized with water using a magnetic stirrer. Ag-NPs were fabricated using the marine brown alga Turbinaria turbinata and loaded on olive oil nanoemulsion (Ag/NEM-olive oil). The TEM image showed a very small size for both NEM-olive oil (7 to 15 nm) and Ag/NEM-olive oil (3.00–10.2 nm). The zeta potential values indicate that Ag/NEM-olive oil possessed more negative charge (−35.5 mV) than NEM-olive oil (−19.8 mV), which proved that Ag/NEM-olive oil was more stable. The nanoparticles showed good anticancer activities against the CACO-2 cell line and Hep G2 in vitro but less than the doxorubicin standard anticancer drug. The nanoparticles showed good antimicrobial activities against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis (ATCC 29212) (Gram-positive), Escherichia coli ATCC 35218 (Gram-negative), and Candida albicans ATCC 76615 (fungus). The nanoemulsion has good biocompatibility owing to the high content of fatty acids such as hexadecanoic acid, oleic acid, and octadecanoic acid, which was confirmed by GC-MS analysis. Nanoemulsions exhibited a wide range of applications, such as drug delivery, antimicrobial, and anticancer activities, and can also be used in the cosmetic and dermatological fields. Nanoemulsions can be synthesized by low-energy methods with high productivity and robustness, making manufacturing scale-up easy.

ragaa.hamouda@gebri.usc.edu.eg, ragaahom@yahoo.com

Acknowledgments

This work was funded by the University of Jeddah, Jeddah, Saudi Arabia, under grant No. (UJ-23 DR-269). The authors acknowledge the technical and financial support of the University of Jeddah. The authors thank Dr. Khadejah Moeed Alqurni, Faculty of Applied Medical Sciences, Jeddah, Saudi Arabia, for providing microorganisms.

Funding information: This work was funded by the University of Jeddah, Jeddah, Saudi Arabia, under grant No. (UJ-23-DR-269).
Author contributions: R.A.H.: conceptualization, data analysis, methodology, validation writing and reviewing; A.A.S.: resources, B.A.E.: antimicrobial methodology and resources.
Conflict of interest: Authors state no conflict of interest.
Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2024-02-04

Accepted: 2024-05-22

Published Online: 2024-06-26

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

https://doi.org/10.1515/gps-2024-0026

Keywords for this article

marine algae; olive oil; nanoemulsion; anticancer; antioxidant; antimicrobial

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