XRD pattern was illustrated in Figure (2). The plotted results, in which the characteristic XRD peaks of rutile (tetragonal phase) and gold (cubic phase) appeared according to Brucker database software COD 1100138 and COD 9004143 for gold and rutile nanoparticles, respectively. A typical XRD pattern for carbopol gel (amorphous phase) was exhibited where no peaks have been noticed.
Transmission Electron Microscope (TEM) and Scanning Electron Microscope (SEM) studies
TEM and SEM images illustrated the homogeneity of size and shape of gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel. It can be obviously noticed a good hybridization with a carbopol gel matrix (Figs. 3–10). TEM (black and colored) images proved the sub-spherical shape of gold and rutile nanometals. The good conjugation of the nanomaterials with the gel matrix was observed, which were surrounded by sheets of the carbopol polymer as revealed in Figs. 3 to 6. The SEM images clarified the coating of the gel matrix to gold and rutile nanometals, which enhances their stabilization (Figs. 9 and 10). In the previous studies, comparable findings were obtained by Kao et al. (2006), and Tzankov et al. (2013). They mentioned that the nanoparticles were uniformly distributed in the carbopol gel, and the size and shape of the nanoparticles were not altered by carbopol coating. Thus, such evenly hybrid nanocomposites are helpful for pharmacological purposes because they provide outstanding absorption and dispersion.
Atomic force microscope (AFM) study
2D and 3D AFM images were studied to illustrate the shape of gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel in contact with the gel matrix and its roughness profile. First of all, the samples were initially prepared before testing as follows; 1 mL of sample was diluted in 10 mL of doubled distilled water, then they were subjected to the sonication process at a condition of amplitude 98% and cycle 0.9 for 1 h using ultrasonic prop instrument. The prepared samples were placed on a clean laboratory glass slide and left for one minute and were air-dried for 24 hours before measuring on an AFM instrument using a gold tap and in a non-contact mode. 2D and 3D AFM images (Fig. 11) illustrated the spherical shape of the samples and the sheet structure of the gel matrix that interconnected the particles and appeared in a good homogenous size and shape distribution.
Surface area and pore size
The surface area measured by the BET method illustrates the high surface area of both gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel. However, gold/carbopol hybrid nanogel has a BET surface area of 43 m2/g, while titanium dioxide/carbopol hybrid nanogel has a BET surface area of 34 m2/g. However, these values were less than gold nanometals and rutile but still more than bulk ones [35]. Pore size measured by Dubinim-Astakhov (DA) method illustrates the mesoporous feature of both gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel (Figs. 12, 13). However, gold/carbopol hybrid nanogel has a total pore size of 2.35 nm, while titanium dioxide/carbopol hybrid nanogel has 3.4 nm. The Isotherm curve of prepared compounds declares the V-type isotherm (Figs. 12 and 13). Where this type of adsorption isotherm is obtained when intermolecular attraction effects are large, and adsorption takes place in pores and capillaries. Besides, porous materials and materials have a weak interaction between the adsorbate and adsorbent. This indicates that the carbopol gel possesses a large area of pores and capillaries. On the other hand, the interaction between the carbopol and the nanomaterials is physical in nature. These results mean that the gold and rutile/carbopol matrix nanocomposite gel exhibit better processibility, availability in different forms and nature, ease of tailoring to different forms, and long-term stability during applications.
DLS and zeta-potential
DLS and zeta potential measurements were carried out to study the hydrodynamic diameter and surface charge of the synthesized colloidal gold and titanium dioxide NPs. DLS for both gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel showed homogeneity in size where they have one sharp peak at 32 nm and 51 nm, respectively. While the size of both gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel were 45 nm and 67 nm, respectively. The big size of both gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel can be accounted for the good coating of gold nanometals and rutile with gel matrix on their surfaces. The Zeta-potential of gold and titanium dioxide nanoparticles was found to be + 22 and − 28 mV, respectively.
Cytotoxicity and associated morphological changes of Gold/carbobol gel on the wi38 cells at different concentrations 1000, 500, 250, 125.5, 62.5 and 31.25 ug/mL using methyl-thiazolyl tetrazolium protocol (MTT)
Determination of cytotoxicity of titanium dioxide NPS and gold NPS on normal human diploid cell line (WI-38 cell) depending on (MTT protocol) Cytotoxicity of titanium dioxide NPS and gold NPS on normal human diploid cell line (WI-38 cell) depending on (MTT protocol) and IC50 values were found to be 302.96 and 382.99 ug /mL for titanium dioxide /carbopol nanogel and gold /carbopol nanogel in Table (1), respectively.
Table (1). Cytotoxicity results of titanium dioxide and gold nanoparticles against wi38 cells using MTT protocol.
ID | ug/ml | O.D | Mean O.D | ±SE | Viability % | Toxicity % | IC50 ± SD |
Wi38 | -------- | 0.638 | 0.622 | 0.645 | 0.635 | 0.006807 | 100 | 0 | ug |
TiO2 | 1000 | 0.024 | 0.021 | 0.022 | 0.022333 | 0.000882 | 3.517060367 | 96.48293963 | 302.96 ± 4.47 |
500 | 0.064 | 0.047 | 0.052 | 0.054333 | 0.005044 | 8.556430446 | 91.44356955 |
250 | 0.352 | 0.337 | 0.341 | 0.343333 | 0.004485 | 54.06824147 | 45.93175853 |
125 | 0.617 | 0.593 | 0.603 | 0.604333 | 0.00696 | 95.17060367 | 4.829396325 |
62.5 | 0.634 | 0.63 | 0.622 | 0.628667 | 0.003528 | 99.00262467 | 0.997375328 |
31.25 | 0.637 | 0.618 | 0.635 | 0.63 | 0.006028 | 99.21259843 | 0.787401575 |
Nano Gold | 1000 | 0.048 | 0.055 | 0.05 | 0.051 | 0.002082 | 8.031496063 | 91.96850394 | 382.99 ± 12.65 |
500 | 0.153 | 0.184 | 0.199 | 0.178667 | 0.013544 | 28.13648294 | 71.86351706 |
250 | 0.463 | 0.481 | 0.479 | 0.474333 | 0.005696 | 74.69816273 | 25.30183727 |
125 | 0.611 | 0.634 | 0.625 | 0.623333 | 0.006692 | 98.16272966 | 1.837270341 |
62.5 | 0.635 | 0.641 | 0.622 | 0.632667 | 0.005608 | 99.63254593 | 0.367454068 |
31.25 | 0.629 | 0.631 | 0.642 | 0.634 | 0.004041 | 99.84251969 | 0.157480315 |
Effect of Nano Gold on wi38 cells at different concentrations
Figure (15): Cell viability at various doses monitored and correlated with large-scale morphological changes at the cell surface or in the cytoskeleton compared to control at different concentrations 1000,500,250,125,62.5 and 31.25 ug/ml.
Effect of Nano Gold on wi38 cells at different concentrations
Figure (17). Cell viability at various doses monitored titanium dioxide nanogel and correlated with large-scale morphological changes at the cell surface or in the cytoskeleton compared to control at different concentrations 1000, 500, 250, 125, 62.5 and 31.25 ug/mL.
Figure (18). Effect of titanium dioxide on wi38 cells at different concentrations.
In vitro anti-inflammatory activity
In vitro anti-inflammatory by using Human red blood cell haemolysis and membrane stabilization assay
The anti-inflammatory activity was determined for gold/carbopol nanogel and titanium dioxide/carbopol nanogel in vitro by human RBCs membrane stabilization technique. The assessment of human red blood cell (RBC) membrane stabilization involves a technique used to assess how well a substance can protect the RBC membrane from harm. This method relies on the concept that specific substances have the ability to stabilize the RBC membrane and prevent the breakdown of RBCs when they are exposed to stressors. The level of hemolysis, which is the disintegration of RBCs, is subsequently measured using spectrophotometer or other methods such as the measurement of hemoglobin release. The extent to which the RBC membrane is stabilized can be measured by determining the percentage of inhibition of hemolysis. This assay is also utilized to evaluate the potential harmful effects of drugs and chemicals on RBC membranes. The obtained results exhibited that titanium dioxide/carbopol nanogel had a strong anti-inflammatory activity resembles that of standard (indomethacin). Gold/carbopol nanogel is considered superior and potential than all groups. Indomethacin produced an inhibition of hemolytic percent of 99.6, 96.2, 94.6 and 93.4 in comparison to 97.1, 94.2, 91.2, and 87.3% to those of tittanium dioxide/carbopol nanogel and 99.5, 95.9, 92.6, and 91.4% to those of gold/carbopol nanogel when used at concentrations of 1000, 800, 600 and 400 µg/mL, respectively, as shown in Table (2) and Figures (19–22).
Table 2
Effect of Standard Indomethacin and gold/carbopol nanogel than titanium dioxide/carbopol nanogel on hemolysis inhibition %.
Conc. ug/ml | haemolysis Inhibition % Standard (Indo.) | SE | Haemolysis Inhibition % gold/carbopol nanogel | SE | Haemolysis Inhibition % titanium dioxide/carbopol nanogel | SE |
1000 | 97.2 | 0.001 | 96.3 | 0.000 | | 0.000 |
800 | 95.8 | 0.001 | 94.6 | 0.000 | | 0.000 |
600 | 94.2 | 0.001 | 91.4 | 0.000 | | 0.000 |
400 | 92.1 | 0.001 | 88.3 | 0.001 | | 0.001 |
200 | 91.0 | 0.002 | 86.4 | 0.000 | | 0.000 |
100 | 90.1 | 0.000 | 85.1 | 0.001 | | 0.001 |
Antimicrobial activity
Developing new therapeutic inorganic antibacterial nanoparticle substances that have minor or no side effects and are easily implemented is of great importance and catches the attention of pharmaceutical researchers (Mirzajani et al., 2011). In our study, two types of microorganisms, S. aureus and C. albicans were selected due to their clinical importance in both humans and animals, especially in livestock and small animals. S. aureus and C. albicans cause severe lesions in open wounds and the oral cavity, which reflects on human and animal performance and productivity. Agar diffusion was used to measure antimicrobial activity, with a disc diameter of 6.0 mm (100 µL) being examined. All materials were dissolved at a concentration of 10 mg/mL in either DMSO or sterile saline (0.9 percent NaCl). Against all the pathogenic strains that were examined, saline lacked antibacterial action. Based on our study, results of molecular docking and in vitro antimicrobial activity showed potential antimicrobial efficacy of gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel against Candida albicans (ATCC 10221) and S. aureus (ATCC 6538) compared to gentamicin as a control group. The data were represented graphically in Fig. 16 and tabulated in Table 3.
Titanium dioxide/carbopol hybrid nanogel showed better results in comparison with control gentamicin. The zone of inhibitions of titanium dioxide/carbopol hybrid nanogel were (16.8 ± 0.4 and 25.8 ± 0.3 mm) compared to control (12.8 ± 0.4 and 20.2 ± 0.4 mm) against Staph. aureus and Candida albicans, respectively (Table 3). MIC value of titanium dioxide/carbopol hybrid nanogel was (29.6 ± 0.5 and 80.6 ± 0.7 mm) against Staph. aureus and Candida albicans, respectively (Table 2). The efficacy of titanium dioxide/carbopol hybrid nanogel may be attributed to its stability, morphology, and its resistance to a wide range of microbes (Jayaseelan et al., 2013). Referring to the results recorded by Rezaee and Kermanshahi (Koseki et al., 2008), TiO2/carbopol nanogel with a size of 21 nm and 1% concentration have minimum inhibitory concentrations (MIC) and minimum bactericidal concentration of 0.5%. In addition, the results reported by kumar et al. (2017), confirmed that the MIC of TiO2/carbopol nanogel at nano size 33 nm was found to be 30 µg/mL against S. aureus and 40 µg/mL against E. coli. These results assured the relation between NP size and antimicrobial effect (Bahmani et al., 2019). Our characterization results of the prepared titanium dioxide nanogel agreed with the previously reported results, which demonstrated that the size of the prepared sample in our study was 51 nm with zeta potential − 28 mV.
The attachment ability of the NP to sulfhydryl (R-SH), carboxylic(-COOH), and phosphate (PO4)3− groups, which cause their conformational change affects the enzymes and proteins of the respiratory cycle, making the cycle inefficient (Mocan et al., 2014). Bahmani et al. (2019) reported that the antimicrobial activity of TiO2 was attributed to the effect of NPs on proteins, DNA, and enzymes that are critical for cell proliferation. Bacteria bind to NPs due to the presence of a phosphate group, causing them to convert from a flexible to a rigid state, and transformation, rotation, and movement in DNA result in activities like replication and transcription. Inside the cell, nanoparticles also activate free radicals and oxygen, both of which have antibacterial properties.
Table 3 Demonstrated inhibition zone (mm) and the MIC50 (µg/mL) of gold/carbopol hybride nano gel and TiO2/carbopol hybrid nanogel against Staph. aureus and Candida albicans.
| Inhibition zone (mm/mg) | MIC50 µg/mL |
Staph. aureus (ATCC 6538) | Candida albicans (ATCC 10221) | Staph. Aureus (ATCC 6538) | Candida albicans (ATCC 10221) |
Gold/carbopol hybrid nanogel | 23.2 ± 0.7a | 32.8 ± 0.4 a | 4.2 ± 0.37c | 3.2 ± 0.7c |
Titanium dioxide/carbopol hybrid nanogel | 16.8 ± 0.4b | 25.8 ± 0.3 b | 29.6 ± 0.5a | 80.6 ± 0.7a |
Control: Gentamicin | 12.8 ± 0.4c | 20.2 ± 0.4 c | 19.6 ± 0.51b | 48.8 ± 0.7b |
Statistical analysis was carried out by one-way ANOVA followed by Duncan’s multiple comparison tests.
(a) Significant difference from control and titanium/carbopol hybride nanogel group at P < 0.05.
(b) Significant difference from control and gold/carbopol hybrid nanogel group at P < 0.05.
(c) Significant difference from gold/carbopol hybrid nanogel, control, and titanium/carbopol hybrid nanogel group at P < 0.05.
Another suggested explanation depends on the germicidal mechanisms of TiO2 nanoparticles. This mechanism involves the release of positively charged ions into the reaction medium where they are linked to the negatively charged thiol group (-SH) of the proteins on the cytoplasmic membrane (Singh et al., 2018). This process will cause the cell wall to be captured, the permeability to increase, and the structure of cellular elements including DNA, ribosomes, and cellular enzymes to deform, all of which will result in the death of microbial cells (Mocan et al., 2014).
Our results agreed with Kumar et al. (2017) who confirmed the antibacterial effect of gold nanoparticles against Staphylococcus aureus. In addition, Mocan et al. [46] reported that gold nanoparticles increased the methicillin-resistant Staphylococcus aureus (MRSA) necrosis death rate in a short cultivation time. Singh et al. (2017) informed that the synthesized crystalline nanoparticles with a diameter between 12 and 18 nm showed bactericidal effects against Pseudomonas aeruginosa and Escherichia coli.
From previously published articles concerning the antibacterial action of GNPs, it was found two ways to explain the antibacterial mechanism (Cui et al., 2012). The first method involved altering membrane potential and preventing ATP synthase from producing more ATP, which decreased the quantity of ATP and triggered metabolic pathways that result in anabolic responses. On the other hand, blocking the binding of tRNA (transfer ribonucleic acid) to the ribosomal subunit caused a blockage of the critical bacterial processes. Additionally, they demonstrated that bactericidal GNPs did not trigger any ROS-related processes and that they enhanced chemotaxis in the early phases of the response (Martinez-Castanon et al., 2008).
The results of MIC values of gold and titanium dioxide nanogels were (4.2 and 29.6 µg/mL) and (3.2 and 80.6 µg/mL) for Staph. Aureus and Candida albicans, respectively. These results agreed with Shamaila et al. (2016), who reported that the MIC values of gold nanoparticles with diameters of 34 nm were 2.93 µg/mL, 7.56 µg/mL, 3.92 µg/mL, and 3.15 µg/mL for E. coli, B. subtilis, S. aureus, and K. pneumonia, respectively. The MICs of gold nanoparticles with sizes of 20–40 nm were 2.96 µg/mL, 8.61 µg/mL, 3.98 µg/mL, and 3.3 µg/mL for E. coli, B. subtilis, S. aureus, and K. pneumonia, respectively. According to Mahdy et al. (2017), the minimum inhibition concentration of TiO2 nanoparticles determined by broth dilution method at nano size 33 nm was found to be 30 µg/mL for S. aureus and 40 µg/mL for E. coli. The potential antimicrobial activity of gold nanogel may be attributed to its unique mechanism of action on the cell membranes, its ability in combination with other drugs, its electrostatic and hydrophobic interactions, and its ability in changing the membrane potential.
Molecular docking study
Gold/carbopol hybrid nanogel
The binding mode of gold particle exhibited an energy binding of -3.20 kcal/mol against Microbial Beta-Ketoacyl-ACP Synthase II complexed with Malonyl-COA (PDB ID: 1HNJ). Three interactions were formed with Ile 156, Met 207, and Val 212 via hydrogen bonding. The gold particle can interfere with the binding of the phosphate group of malonyl COA (Fig. 14 A, B). When calculating the Root Mean Square Deviation (RMSD), the co-crystallized compound was re-docked into the crystal structure's active pocket and the complex was overlaid on the original crystal structure. The RMSD (Å) value calculated for gold/carbopol hybrid nanogel is 0.86. The validation of the docking process is considered accurate if the RMSD value is less than 2 [36, 37].
Titanium dioxide/carbopol hybrid nanogel
The binding mode of titanium dioxide exhibited an energy binding of -2.87 kcal/mol against Microbial Beta-Ketoacyl-ACP Synthase II complexed with Malonyl-COA (PDB ID: 1HNJ). The interaction with Asn 247 by one hydrogen bonding can interfere with the binding of the phosphate group of malonyl COA (Fig. 15 A, B). The RMSD value (Å) calculated was 0.67 indicating the validation of the docking protocol [36, 37].
Antioxidant activity 2,2-diphenyl-1-picrylhydrazyl (DPPH method)
At the various doses evaluated (10, 15, 25, 50, 60 g/mL), gold/carbopol hybrid nanogel had higher antioxidant activity comparable to that of titanium dioxide hybrid nanogel and conventional ascorbic acid, Table 2. For all concentrations examined, the percentage of antioxidant activity increased in a dose-dependent manner. In order to measure antioxidant activity using the DPPH technique, ascorbic acid was employed as a reference medication. Ascorbic acid concentrations ranged from 6.25 to 100 ug/mL. The percentage inhibition of ascorbic acid was 73.1% at 6.25 ug/mL and 97.6% at 100 ug/mL as reported in Table 4. Figure 26 showed that gold/carbopol hybrid nanogel has a powerful potential to scavenge hydrogen peroxide as compared to titanium dioxide/carbopol hybrid Nano gel and vitamin C.
Statistical analysis was carried out by one-way ANOVA followed by Duncan’s multiple comparison tests.
(a) Significant difference from control and gold/carbopol hybrid nanogel group at P < 0.05.
(b) Significant difference from control and TiO2/carbopol hybrid nanogel group at P < 0.05.
(c) Significant difference from gold/carbopol hybrid nanogel, control, and TiO2/Carbopol hybrid nanogel group at P < 0.05.
Table 4
Absorbance at various concentrations (µg/mL) of gold/carbopol hybrid nanogel and TiO2 /carbopol hybrid nanogel and ascorbic acid.
(Conc. µg/mL) | Absorbance of gold/carbopol hybrid nanogel | Absorbance of TiO2/carbopol hybrid Nanogel | Absorbance of ascorbic acid |
10 | 0.047 ± 0.001a | 0.031 ± 0.001 b | 0.038 ± 0.001 ab |
15 | 0.103 ± 0.001 a | 0.062 ± 0.001 b | 0.078 ± 0.001 ab |
25 | 0.213 ± 0.001 a | 0.152 ± 0.001 b | 0.163 ± 0.001 ab |
50 | 0.329 ± 0.001 a | 0.272 ± 0.001 b | 0.291 ± 0.001 ab |
60 | 0.410 ± 0.001 a | 0.375 ± 0.001 b | 0.390 ± 0.001 ab |
Statistical analysis was carried out by one-way ANOVA followed by Duncan’s multiple comparison tests.
(a) Significant difference from control and Au/carbopol hybrid nanogel group at P < 0.05.
(b) Significant difference from control and TiO2/carbopol hybride nanogel group at P < 0.05.
(ab) Significant difference from Au/carbopol hybrid nanogel, control, and TiO2/carbopol hybrid nanogel group at P < 0.05.
Table 5
Demonstrated the % of free radical scavenging activity of gold/carbopol hybrid nano gel and TiO2/carbopol hybrid nanogel against ascorbic acid.
(Conc. µg/mL) | DPPH scavenging% of gold/carbopol hybrid nano gel | DPPH scavenging % of TiO2/carbopol hybrid nano gel | DPPH scavenging% of ascorbic acid |
60 | 98.7a | 93.4b | 97.6 ab |
50 | 95.5 a | 90.8 b | 91.1 ab |
25 | 92.2 a | 86.2 b | 87.8 ab |
15 | 85.2 a | 80.4 b | 82.1 ab |
10 | 79.6 a | 71.5 b | 73.1 ab |
Statistical analysis was carried out by one-way ANOVA followed by Duncan’s multiple comparison tests.
(a) Significant difference from control and Au/carbopol hybrid nanogel group at P < 0.05.
(b) Significant difference from control and TiO2/carbopol hybrid nanogel group at P < 0.05.
(ab) Significant difference from Au/carbopol hybrid nanogel, control, and TiO2/Carbopol hybrid nanogel group at P < 0.05.
Activity against molluscs
Activity against the mollusk Lymnea stagnalis:
The data represented in Table (4) showed the results of the study and evaluation of the molluscicidal activity of gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel on the Lymnea stagnalis snail with increasing tested concentrations and exposure. According to the gold/carbopol hybrid nanogel data, when the exposure time was extended along with an increase in the evaluated gold/carbopol hybrid nanogel concentration, the mortality rate increased. The percentage of mortality of the Lymnea stagnalis snail exposed to the gold/carbopol hybrid nanogel ranged from 0% at a concentration of 0.312 ppm of the tested nanomaterial at an exposure time of 3 hours to 10% after 6 hours to 20% after 12 hours at the same concentration, 30% at 1.25 ppm after 3 hours of exposure, 40% after 6 hours to 60% after 12 hours at the same concentration, and 50% at a concentration of 0.625 ppm after 24 hours of exposure. At a dosage of 5 ppm, the greater mortality rate was 80% after 3 hours and 90% after 6 hours of exposure. The highest percentage of death, 100%, was obtained at 1.25 ppm at a 24-hour exposure time, followed by 5 ppm at a 12- hour exposure period, 10 ppm at a 6- hour exposure period, and 20 ppm at a 3- hour exposure period. However, using the same titanium dioxide/carbopol hybrid nanogel concentrations, no mortalities of the Lymnea stagnalis snail were detected.
According to the gold/carbopol hybrid nanogel data, when the exposure time was extended along with an increase in the evaluated gold/carbopol hybrid nanogel concentration, the mortality rate increased. The percentage of mortality of the Lymnea stagnalis snail exposed to the gold/carbopol hybrid nanogel ranged from 0% at a concentration of 0.312 ppm of the tested nanomaterial at an exposure time of 3, 6, 12 and 24 hours while at a concentration of 0.625 ppm showed 10% after 6 hours to 30% after 12 hours at the same concentration and 50% after 24 h. On the other hand, at concentration of 1.25 ppm showed 20% after 3 hours to 50% after 6 hours at the same concentration and 50% after 12 h and 70% after 24 h. On the other hand, at concentration of 2.5 ppm, it showed 40% after 3 hours to 60% after 6 hours at the same concentration and 80% after 12 h and 100% after 24 h. However, at concentration of 5 ppm, it showed 50% after 3 hours to 70% after 6 hours at the same concentration and 80% after 12 h and 100% after 24 h. Finally, at concentration of 10 ppm, it showed 70% after 3 hours to 100% after 6 hours and after 12 h and 24 h. at the same concentration.
Table 6
Effect of the gold/carbopol hybrid nanogel against Lymnea stagnalis snail.
The tested gold / carbopol hybrid nanogel concentrations | Period of exposure of lymnea stagnalis snails to gold/carbopol hybrid nanogel | Mortalities in 10 Lymnea stagnalis snails |
No. of dead snails /10 snails | Percentage of mortality |
0.312 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
0.625 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 1/10 3/10 5/10 | 0% 10% 30% 50% |
1.25 ppm | Three hours Six hours Twelve hours Twenty-four hours | 2/10 5/10 7/10 9/10 | 20% 50% 70% 90% |
2.5 ppm | Three hours Six hours Twelve hours Twenty-four hours | 4/10 6/10 8/10 10/10 | 40% 60% 80% 100% |
5 ppm | Three hours Six hours Twelve hours Twenty-four hours | 5/10 7/10 8/10 10/10 | 50% 70% 80% 100% |
10 ppm | Three hours Six hours Twelve hours Twenty-four hours | 7/10 10/10 10/10 10/10 | 70% 100% 100% 100% |
Activity against the snail Biomphalaria alexandrina:
The study and evaluation of the molluscicidal activity of gold/carbopol hybrid nanogel and titanium dioxide/carbopol hybrid nanogel on Biomphalaria alexandrina snail with increasing concentration and exposure to the investigated nanomaterials are shown in Table (3). Results for the gold/carbopol hybrid nanogel indicated that when the concentration of the tested nanomaterial grew and the exposure time was prolonged, the mortality % also did so. At concentrations of 0.3125 ppm to 10 ppm of the tested gold/carbopol hybrid nanogel, mortality of the Biomphalaria alexandrina snail was found to be 0% at exposure times of 3 hours, 6 hours, 12 hours, and 24 hours. However, at a concentration of 20 ppm, mortality of the snail was found to be 10% at exposure times of 6 hours, 20% at exposure times of 12 hours, and 40% at exposure times of 24 hours. At 40 ppm concentration of the tested gold/carbopol hybrid nanogel was shown to result in mortality rates of 10% after 3 hours, 20% after 6 hours, 30% after 12 hours, and 50% after 24 hours. At an exposure level of 80 ppm, the mortality rate was determined to be 40% after 3 hours, 60% after 6 hours and 90% after 12 h. At a concentration of 80 ppm with an exposure period of 24 hours, 100% mortality of Biomphalaria alexandrina snail was induced, making it the highest percentage of mortality that was recorded among all the tested concentrations. The higher mortality percentage was found to be 90% after 12 h of exposure and 100% after 24 hours of exposure to the same concentration, which is 80 ppm. Using the identical concenterations of the titanium dioxide/carbopol hybrid nanogel, however, no deaths of the Biomphalaria alexandrina snail were noted.
In tropical areas, schistosomiasis negatively impacts human health. Its prevention is more crucial than its treatment, which increases the demand for efficient management strategies. The use of nanomaterials in medical research has increased recently.
Table 7
Effect of the gold/carbopol hybrid nanogel against Biomphalaria alexandrina snail.
The tested gold/ carbopol hybrid nanogel concentrations | Period of exposure of lymnea stagnalis snails to gold/ carbopol hybrid nanogel | Mortalities in 10 Biomphalaria alexandrina snails |
No. of dead snails /10 snails | Percentage of mortality |
0.312 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
0.625 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
1.25 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
2.5 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
5 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
10 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 0/10 0/10 0/10 | 0% 0% 0% 0% |
20 ppm | Three hours Six hours Twelve hours Twenty-four hours | 0/10 1/10 2/10 4/10 | 0% 10% 20% 40% |
40 ppm | Three hours Six hours Twelve hours Twenty-four hours | 2/10 3/10 4/10 7/10 | 10% 20% 30% 50% |
80 ppm | Three hours Six hours Twelve hours Twenty-four hours | 3/10 5/10 8/10 10/10 | 40% 60% 90% 100% |
The second most common parasite disease in the world, behind malaria, is schistosomiasis. According to the WHO (2015), it affects over 260 million people and results in 200,000 fatalities annually. According to Hotez et al. (2012), the Middle East and North Africa region has 12.7 million infected people, with 7.2 million of them living in Egypt. In Egypt, where a non-integrated intervention approach is still in place and infection is still being transmitted in high-risk areas of the Nile Delta, the rate of transmission has been significantly reduced. Consequently, new, all-encompassing control measures are still required (Barakat et al. 2014). The biomedical sciences have recently made extensive use of nanoparticles (NPs) to make it easier to administer antibiotics and lessen their negative effects. The advantages of the NPs are further enhanced by their ultra-small size, high surface-area-to-mass ratio, and reactivity. (Zhang et al. 2010).
Au NPs have also shown potential as insecticides (Teimouri et al. 2018). On arthropod vectors such ticks, tsetse flies, tabanid flies, sand flies, and black flies, as well as additive-related ecotoxicological experiments, the impacts of Au NPs are documented (Benelli 2018). By serving as a drug vehicle for commonly prescribed medications, including praziquantel in the treatment of schistosomiasis, NPs exhibit powerful antiparasitic effects (Kolenyak-Santos et al. 2014). Au NPs exhibit an anti-neuroschistosomal impact in mice infected with Schistosoma mansoni, proving that NPs themselves can have direct antiparasitic action (Dkhil et al. 2015a). Few researches have looked into the use of NPs as molluscicides or cercaricides. El-Hommossany and El-Sherbibni (2011) found that Au NPs reduced the ability of Biomphalaria alexandrina to reproduce and killed Bulinus truncatus snails.
Also, Moustafa et al. (2018) analyzed the possible impacts of gold nanoparticles on Biomphalaria alexandrina snails and Schistosoma mansoni cercariae in vitro. According to the in vitro investigation, the concentrations of 30 g/mL Ag and 160 g/mL Au resulted in 100% mortality in B. alexandrina snails. Au NPs can prevent or reduce cercariae infectivity in vivo and have promise as molluscicides and cercaricides in vitro.
Wound healing activity
Figure 20 showed the effect of topical application of gold/carbopol hybrid nano gel and TiO2/carbopol hybrid nanogel compared to control negative and standard group on wound area (mm2) in rabbits.
Results of Histopathological examination demonstrated the superior wound healing efficacy of GNPs treated group compared to other groups as demonstrated in Fig. 20. Figure 20A illustrated that wounded non treated group (Group I) showed thickened epidermal layer with congested blood vessels and diffuse lymphocytic cells infiltration within dermal layer. While Fig. 20B showed that standard control group (Group II) revealed intact epidermal and dermal layer with well-formed hair follicles and sebaceous glands distributed within collagen and fibrous tissue. On the other hand, Fig. 20C showed that TiNPs treated group (Group III) showed regenerated tissue in which cellular granulation tissue is formed with few hair follicles. The results given in Fig. 20D showed that GNPs treated group characterized by ulcerative epidermal layer with remarkable destruction of dermal layer fibrous tissue.
The prospective role of titanium dioxide in the promotion of cell development and antibacterial effects on wound healing [50]. Priorities for wound healing include hastening the healing process and guarding against wound infections. Thus, it is anticipated that nano titanium dioxide will have both of these effects, which will improve functional recovery and promote wound healing [51].