Chitosan-sialic acid nanoparticles of selenium: Statistical optimization of production, characterization, and assessment of cytotoxic effects against two human glioblastoma cell lines.

According to the favorable antitumor properties of selenium, this study aimed to design a novel form of selenium nanoparticles (Se NPs) functionalized with chitosan (Cs) and sialic acid to assess their antitumor effects on the human glioblastoma cell lines (T98 and A172). Se NPs were synthesized in the presence of chitosan and ascorbic acid (Vc) and the synthesis conditions were optimized using response surface methodology. Se NPs@Cs were obtained with a monoclinic structure with an average diameter of 23 nm under the optimum conditions (reaction time = 30 min, chitosan concentration = 1 % w/v, Vc/Se molar ratio = 5). To modify Se NP@Cs for glioblastoma treatment, sialic acid was used to cover the surface of the NPs. Sialic acid was successfully attached to the surface of Se NPs@Cs, and Se NPs@Cs-sialic acid were formed in the size range of 15-28 nm. Se NPs@Cs-sialic acid were stable for approximately 60 days at 4 ℃. The as-synthesized NPs exerted inhibitory effects on T98 greater than 3 T3 > A172 cells in a dose- and time-dependent manner. Additionally, sialic acid ameliorated the blood biocompatibility of Se NPs@Cs. Taken together, sialic acid improved both the stability and biological activity of Se NPs@Cs.

Rapid microwave-assisted biosynthesis of platinum nanoparticles and evaluation of their antioxidant properties and cytotoxic effects against MCF-7 and A549 cell lines.

In this study, platinum nanoparticles (Pt NPs) were synthesized by a green method using an aqueous extract of Eucalyptus camaldulensis with assistance of microwave irradiation (850 W) and their physicochemical characteristics were studied by UV-visible spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) analyses. Antioxidant activities, hemocompatibility, and cytotoxic effects of the prepared Pt NPs were then evaluated. The attained results showed that the newly formed Pt NPs possess a size range between 7.4 and 11.2 nm. These spherical-shaped NPs were slightly aggregated and held various functional groups on their surface. The antioxidant activity of Pt nanostructures was comparable to that of butylated hydroxyl anisole at concentrations higher than 320 µg/mL. At the same concentration of 640 µg/mL, the scavenging activities were 3.36 ± 0.9% (hexachloroplatinic acid) and 52.13 ± 0.43% (Pt NPs). The results of hemolytic assay revealed satisfactory hemocompatibility of the Pt NPs even at the concentration as high as 4 mg/mL (hemolysis percent equal to 3.5 ± 1.3%). The cytotoxicity studies revealed that MCF-7, A549, and 3T3 cell lines treated with hexachloroplatinic acid and cisplatin for 24 h and 48 h showed a higher percentage of cell death compared with the Pt NPs. After 24 h, for A549, 3T3, and MCF-7 cells exposed to Pt NPs, the cell viability was measured to be 80 ± 3.2%, 96 ± 1%, and 89 ± 2.6%, respectively, at concentration of 640 µg/mL. Further investigations are required to elucidate the mechanisms behind the biological activities of as-synthesized Pt NPs.

Rapid and Facile Microwave-Assisted Synthesis of Palladium Nanoparticles and Evaluation of Their Antioxidant Properties and Cytotoxic Effects Against Fibroblast-Like (HSkMC) and Human Lung Carcinoma (A549) Cell Lines.

We report here a simple microwave irradiation method (850 W, 3 min) for the synthesis of palladium nanoparticles (Pd NPs) using ascorbic acid (as reducing agent) and sodium alginate (as stabilizer agent). The synthesized nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-Visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Antioxidant properties and cytotoxic effects of as-synthesized Pd NPs and Pd (II) acetate were also assessed. UV-Vis study showed the formation of Pd NPs with maximum absorption at 345 nm. From TEM analysis, it was observed that the Pd NPs had spherical shape with particle size distribution of 13-33 nm. Based on DPPH radical scavenging activity and reducing power assay, the antioxidant activities of Pd NPs were significantly higher than the Pd (II) acetate (p < 0.05). At the same concentration of 640 µg/mL, the scavenging activities were 32.9 ± 3.2% (Pd (II) acetate) and 27.2 ± 2.1% (Pd NPs). For A549 cells treated 48 h with Pd NPs, Pd (II) acetate, and cisplatin, the measured concentration necessary causing 50% cell death (IC50) was 7.2 ± 1.7 µg/mL, 32.1 ± 2.1 µg/mL, and 206.2 ± 3.5 µg/mL, respectively. On HSkMC cells, the IC50 of the Pd NPs (320 µg/mL) was higher compared to Pd (II) acetate (228.7 ± 3.6 µg/mL), which confirmed lower cytotoxicity of the Pd NPs.

Hydrogels For Peptide Hormones Delivery: Therapeutic And Tissue Engineering Applications.

Peptides are the most abundant biological compounds in the cells that act as enzymes, hormones, structural element, and antibodies. Mostly, peptides have problems to move across the cells because of their size and poor cellular penetration. Therefore, a carrier that could transfer peptides into cells is ideal and would be effective for disease treatment. Until now, plenty of polymers, e.g., polysaccharides, polypeptides, and lipids were used in drug delivery. Hydrogels made from polysaccharides showed significant development in targeted delivery of peptide hormones because of their natural characteristics such as networks, pore sizes, sustainability, and response to external stimuli. The main aim of the present review was therefore, to gather the important usages of the hydrogels as a carrier in peptide hormone delivery and their application in tissue engineering and regenerative medicine.

Ondansetron enhanced diclofenac-induced nephrotoxicity in mice.

This study was performed to investigate the effect of ondansetron, a serotonin receptor (5-HT3) antagonist, in the alleviation of diclofenac-induced kidney injuries. NMRI mice were randomly divided into six groups and treated with (A) untreated control group, (B) diclofenac (100 mg/kg), (C) ondansetron (1 mg/kg), (D to F) ondansetron (0.1, 0.5, and 1 mg/kg, respectively) and diclofenac (100 mg/kg) for last 3 days of experiment. The oxidative stress tests strongly demonstrated the negative synergistic effects of diclofenac and ondansetron, regarding the observation of dose-dependent enhancement of malondialdehyde concentration, and reduction of glutathione content, and superoxide dismutase and catalase activity. Histopathological analyses revealed dose-dependent tubular epithelial cells degeneration, outstanding mononuclear cells infiltration, clear necrosis at the papillary region of kidney, dilation, and vascular hyperemia in mice kidney tissues treated with ondansetron and diclofenac. Conclusively, these findings suggested the possible ondansetron-diclofenac interaction through the induction of oxidative stress.

Toxicity of microwave-assisted biosynthesized zinc nanoparticles in mice: a preliminary study.

This study was designed to describe the oral acute and subacute toxicities and underlying toxicological mechanisms of biogenic Zn NPs in mice. The Zn NPs were prepared by a green microwave-assisted synthesis method in the presence of Lavandula vera leaf extract. Determination of median lethal dose (LD50) of Zn NPs and the subacute toxicity after 14 days of exposure was performed as a measurement of substance toxicity through general toxicological, hematological, serum, and histopathological investigations. The western blotting was used to determine the cleaved-caspase-3 expression in the sampled tissues. Flame atomic absorption spectrophotometer (AAS) was applied to estimate the Zn levels in tissues. The SEM analyses revealed that the biogenic Zn NPs were spherical-shaped with the size range of 30-80 nm. The LD50 value above 5 g/kg indicated that biogenic Zn NPs could be classified as non-toxic chemicals. In subacute toxicity, no significant differences were found in the body weight as well as hematological and oxidative stress (OS) biomarkers after exposure to Zn NPs at the dose of 1 g/kg in comparison to the control. The AAS results indicated that Zn NPs were mainly distributed in the testis, liver, and brain. The findings of histology images of Zn NPs at the dose of 1 g/kg were similar to those of the control. Furthermore, no significant differences were observed in cleaved-caspase-3 expression after exposure to Zn NPs at the dose of 5 g/kg. The results demonstrated that changes in the OS were not related to caspase pathway and the no-observed-adverse-effect level (NOAEL) dose of biogenic Zn NPs in 14-days subacute toxicity study was lower than 1 g/kg.

Statistical optimization of kojic acid production by a UV-induced mutant strain of Aspergillus terreus

ABSTRACT The ability of four Aspergillus strains for biosynthesis of kojic acid was evaluated among which Aspergillus terreus represented the highest level (2.21 g/L) of kojic acid production. Improvement kojic acid production ability of A. terreus by random mutagenesis using different exposure time to ultraviolet light (5-40 min) was then performed to obtain a suitable mutant of kojic acid production (designated as C5-10, 7.63 g/L). Thereafter, design of experiment protocol was employed to find medium components (glucose, yeast extract, KH2PO4 (NH4)2SO4, and pH) influences on kojic acid production by the C5-10 mutant. A 25-1 fractional factorial design augmented to central composite design showed that glucose, yeast extract, and KH2PO4 were the most considerable factors within the tested levels (p < 0.05). The optimum medium composition for the kojic acid production by the C5-10 mutant was found to be glucose, 98.4 g/L; yeast extract, 1.0 g/L; and KH2PO4, 10.3 mM which was theoretically able to produce 120.2 g/L of kojic acid based on the obtained response surface model for medium optimization. Using these medium compositions an experimental maximum Kojic acid production (109.0 ± 10 g/L) was acquired which verified the efficiency of the applied method.

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line.

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by Delftia sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC50) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC50 concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.

Cytotoxicity investigations of biogenic tellurium nanorods towards PC12 cell line.

The authors evaluated the cytotoxicity underlying mechanisms of biogenic tellurium (Te) nanorods (NRs) produced by the Pseudomonas pseudoalcaligenes strain Te on the PC12 cell line. The half-maximal inhibitory concentration (IC50) value was estimated at 5.05 ± 0.07 ng/ml for biogenic Te NRs and 2.44 ± 0.38 ng/ml for K2TeO3, respectively. The viability of PC12 was inhibited concentration dependent at doses of 1, 2.5, 5, 10, and 20 ng/ml. Te NRs principally induced late apoptosis or necrosis at IC50 concentration, without effect on caspase-3 activities. Furthermore, Te NRs reduced glutathione and enhanced malondialdehyde levels, and also reduced superoxide dismutase and catalase activities. These findings revealed that biogenic Te NRs were less toxic than K2TeO3. Additionally, they induced cytotoxity towards the PC12 cell line through the activation of late apoptosis independent of the caspase pathway, and may also enhance oxidative stress in the nervous system.

Microwave-assisted biosynthesis of zinc nanoparticles and their cytotoxic and antioxidant activity.

The present study was designed for microwave assisted synthesis of zinc nanoparticles (Zn NPs) using Lavandula vera leaf extract in the presence of ZnSO4 (1mM). The biogenic Zn NPs were then characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), UV-visible spectroscopy, and Fourier transform infrared spectroscopy (FTIR) techniques. Thereafter, the cytotoxic effect of ZnSO4 and Zn NPs on different cell lines was investigated by MTT-based cytotoxicity assay and their antioxidant properties were assessed using DPPH scavenging activity and reducing power assay. The SEM micrograph showed that the Zn NPs had spherical shape with the size range of 30-80nm. For A549, MCF-7, HT-29, and Caco-2 cell lines treated with Zn NPs, the concentration necessary causing 50% cell death (IC50) was found to be 22.3±1.1µgmL-1, 86±3.7µgmL-1, 10.9±0.5µgmL-1, and 56.2±2.8µgmL-1, respectively. In the case of ZnSO4, the same results (IC50) were observed at concentration of 81.6±1.3µgmL-1 (A549), 121.0±2.4µgmL-1 (MCF-7), 43.0±1.4µgmL-1 (HT-29), and 85.7±2.3µgmL-1 (Caco-2). The obtained results of antioxidant activity showed that the IC50 values of butylated hydroxyanisole (BHA) and Zn NPs were 44µgmL-1and 65.3µgmL-1, respectively, while ZnSO4 at concentration of 200µgmL-1 exhibited only 10.9% DPPH radical scavenging effect. Moreover, the reducing power of Zn NPs and BHA were significantly higher than ZnSO4 (p<0.05). To sum up, application of L. vera leaf extract combined with microwave heating energy led to simple and fast formation of Zn nanostructures exhibited higher antioxidant and cytotoxic activity compared to soluble Zn+2 ions. However, identification of the related mechanisms merit further studies.