Synthesis, in silico studies, and in vitro biological evaluation of newly-designed 5-amino-1H-tetrazole-linked 5-fluorouracil analog as a potential antigastric-cancer agent.

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of -7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of - 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy.Communicated by Ramaswamy H. Sarma.

Polyamidoamine Dendrimers Functionalized with ZnO-Chitosan Nanoparticles as an Efficient Surface for L-asparaginase Immobilization.

In this study, the third-generation polyamidoamine dendrimer was functionalized with a 5-amino-1H-tetrazole heterocycle to load the synthesis enzyme and its surface groups. Then, chitosan was attached to the dendrimer by a suitable linker, and finally, zinc oxide nanoparticles were inserted into dendrimer cavities to increase loading. FTIR, FESEM, TEM, and DLS analysis showed that this new dendrimer has specific branches, and ZnO nanoparticles were spread between the branches and connected with the branches and chitosan biopolymer. Also proved the presence of stabilized L-asparaginase enzyme and ZnO nanoparticles in the designed system. Furthermore, the extent of L-asparaginase enzyme loading and release was investigated in the laboratory with a dialysis bag. Examining the toxicity of the new third-generation polyamidoamine (PAMAM) dendrimeric nanocarrier based on chitosan-zinc oxide biopolymer (PAMAM-G3@ZnO-Cs nanocarrier) on the Jurkat cell line (human acute lymphoblastic leukemia) at pH 7.4 showed that this nanocarrier effectively encapsulates the drug L-asparaginase and slowly releases it and also preventing the growth of cancer cells. The activity of the loaded enzyme in the nanocarrier and the free enzyme was calculated. During the investigations, it was found that the enzyme attached to the nanocarrier is more stable than the free enzyme at optimal pH and temperature and at high temperatures, acidic and basic pHs. Vmax and Km values were lower for loaded enzymes. The synthesized PAMAM-G3@ZnO-Cs nanocarrier can be a promising candidate in the pharmaceutical industry and medical science for cancer treatment due to its biocompatibility, non-toxicity, stability, and slow release of L-asparaginase.

Biosynthesis of ternary NiCoFe2O4 nanoflowers: investigating their 3D structure and potential use in gene delivery.

Multicomponent nanoparticle systems are known for their varied properties and functions, and have shown potential as gene nanocarriers. This study aims to synthesize and characterize ternary nickel-cobalt-ferrite (NiCoFe2O4) nanoparticles with the potential to serve as gene nanocarriers for cancer/gene therapy. The biogenic nanocarriers were prepared using a simple and eco-friendly method following green chemistry principles. The physicochemical properties of the nanoparticles were analyzed by X-ray diffraction, vibrating sample magnetometer, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller. To evaluate the morphology of the nanoparticles, the field emission scanning electron microscopy with energy dispersive X-Ray spectroscopy, high-resolution transmission electron microscopy imaging, and electron tomography were conducted. Results indicate the nanoparticles have a nanoflower morphology with a mesoporous nature and a cubic spinel structure, where the rod and spherical nanoparticles became rose-like with a specific orientation. These nanoparticles were found to have minimal toxicity in human embryonic kidney 293 (HEK-293 T) cells at concentrations of 1 to 250 µg·mL-1. We also demonstrated that the nanoparticles could be used as gene nanocarriers for delivering genes to HEK-293 T cells using an external magnetic field, with optimal transfection efficiency achieved at an N/P ratio of 2.5. The study suggests that biogenic multicomponent nanocarriers show potential for safe and efficient gene delivery in cancer/gene therapy.

Fabrication of a Novel and Ultrasensitive Label-Free Electrochemical Aptasensor Based on Gold Nanostructure for Detection of Homocysteine.

The current attempt was made to detect the amino acid homocysteine (HMC) using an electrochemical aptasensor. A high-specificity HMC aptamer was used to fabricate an Au nanostructured/carbon paste electrode (Au-NS/CPE). HMC at high blood concentration (hyperhomocysteinemia) can be associated with endothelial cell damage leading to blood vessel inflammation, thereby possibly resulting in atherogenesis leading to ischemic damage. Our proposed protocol was to selectively immobilize the aptamer on the gate electrode with a high affinity to the HMC. The absence of a clear alteration in the current due to common interferants (methionine (Met) and cysteine (Cys)) indicated the high specificity of the sensor. The aptasensor was successful in sensing HMC ranging between 0.1 and 30 µM, with a narrow limit of detection (LOD) as low as 0.03 µM.

Ultrasensitive FRET-based aptasensor for interleukin-6 as a biomarker for COVID-19 progression using nitrogen-doped carbon quantum dots and gold nanoparticles.

A label-free and specific FRET-based interleukin-6 (IL-6) aptasensor was developed using a DNA aptamer modified with nitrogen-doped carbon quantum dots (NCDs) and gold nanoparticles (AuNPs) as a donor-quencher pair. The assayed target was capable of disrupting the donor-acceptor assemblies yielding a concentration-related fluorescence recovery of NCDs (λem = 445 nm and λex = 350 nm). By designing two different probes, the interaction of DNA aptamers with IL-6 protein was studied using FRET efficiency. It appeared that the sensing probes showed slightly different sensing profiles. One of the aptasensors showed a linear response of 1.5-5.9 pg/mL for IL-6 with a coefficient of determination of R2 ≥ 0.99 and the a detection limit of 0.82 pg/mL (at S/N = 3). The experimental results indicated that the biosensor can be applied to determine IL-6 in human serum (with recovery of 95.7-102.9%). Due to the high sensitivity, excellent selectivity, and simplicity of the procedure, this strategy represents a promising alternative for IL-6 sensing in clinical applications.

Electrochemical enzyme-based blood uric acid biosensor: new insight into the enzyme immobilization on the surface of electrode via poly-histidine tag.

In a new approach, we considered the special affinity between Ni and poly-histidine tags of recombinant urate oxidase to utilize Ni-MOF for immobilizing the enzyme. In this study, a carbon paste electrode (CPE) was modified by histidine-tailed urate oxidase (H-UOX) and nickel-metal-organic framework (Ni-MOF) to construct H-UOX/Ni-MOF/CPE, which is a rapid, sensitive, and simple electrochemical biosensor for UA detection. The use of carboxy-terminal histidine-tailed urate oxidase in the construction of the electrode allows the urate oxidase enzyme to be positioned correctly in the electrode. This, in turn, enhances the efficiency of the biosensor. Characterization was carried out by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), Brunauer-Emmett-Teller (BET), and field emission scanning electron microscopy (FE-SEM). At optimum conditions, the biosensor provided a short response time, linear response within 0.3-10 µM and 10-140 µM for UA with a detection limit of 0.084 µM, repeatability of 3.06%, and reproducibility of 4.9%. Furthermore, the biosensor revealed acceptable stability and selectivity of UA detection in the presence of the commonly coexisted ascorbic acid, dopamine, L-cysteine, urea, and glucose. The detection potential was at 0.4 V vs. Ag/AgCl.

Carbon quantum dots-Annexin V probe: photoinduced electron transfer mechanism, phosphatidylserine detection, and apoptotic cell imaging.

An annexin V-based probe is designed and fabricated using carbon quantum dot as highly stable and biocompatible fluorescent crystals for real-time fluorescence imaging of apoptotic cells. Carbon quantum dots were synthesized, characterized, and conjugated to annexin V. The fluorescence of CQDs at 450 nm (excitation at 350 nm) is quenched due to the photoinduced electron transfer between "carbon quantum dots" and two amino acids (tyrosine and tryptophan) in the annexin structure as quencher. The probe shows very strong and bright fluorescence emission in the presence of phosphatidylserine on the outer layer of the apoptotic cell membrane. It was shown that using fluorescence spectroscopy, the probe can be applied to sensitive phosphatidylserine determination and using fluorescence microscopy, it is possible to monitor cell apoptosis in real time.

Silicon and nitric oxide synergistically modulate the production of essential oil and rosmarinic acid in Salvia officinalis under Cu stress.

The individual impact of silicon (Si) and nitric oxide (NO) on secondary metabolism in several plant species has been reported, but their combined effect has never been evaluated yet. Therefore, in this study, single and combined impacts of NO and Si on the biosynthesis of rosmarinic acid (RA) and essential oil (EO) content in leaves of Salvia officinalis were investigated under both non-stress and Cu stress conditions. The results indicated that high Cu concentration decreased biomass and the content of polyphenols, but elevated electrolyte leakage, while lower Cu concentrations, especially 200 µM Cu, increased the content of polyphenols, EO, and antioxidant capacity in leaves of S. officinalis. The foliar application of sodium silicate (1 mM Si) and sodium nitroprusside (200 µM SNP as a NO donor) alone and particularly in combination improved shoot dry biomass, restored chlorophyll and carotenoids, increased EO content, the amounts of flavonoids, and phenolic compounds especially RA, and enhanced antioxidant capacity in the leaves of S. officinalis under both non-stress and Cu stress conditions. Copper treatment increased NO content, upregulated expression of PAL, TAT, and RAS genes, and enhanced phenylalanine ammonia-lyase activity in the leaves, which were responsible for improving the production of phenolic compounds, particularly rosmarinic acid. Foliar spraying with Si and SNP intensified these attributes. All responses were more pronounced when NO and Si were simultaneously applied under Cu stress. These findings suggest that NO and Si synergistically modulate secondary metabolism through upregulation of related gene expression and enzyme activities under both non-stress and Cu stress conditions.

Biosynthesis of spinel nickel ferrite nanowhiskers and their biomedical applications.

Greener methods for the synthesis of various nanostructures with well-organized characteristics and biomedical applicability have demonstrated several advantages, including simplicity, low toxicity, cost-effectiveness, and eco-friendliness. Spinel nickel ferrite (NiFe2O4) nanowhiskers with rod-like structures were synthesized using a simple and green method; these nanostructures were evaluated by X-ray diffraction analysis, transmission electron microscopy, scanning electron microscopy, and X-ray energy diffraction spectroscopy. Additionally, the prepared nanowhiskers could significantly reduce the survival of Leishmania major promastigotes, at a concentration of 500 µg/mL; the survival of promastigotes was reduced to ≃ 26%. According to the results obtained from MTT test (in vitro), it can be proposed that further studies should be conducted to evaluate anti-leishmaniasis activity of these types of nanowhiskers in animal models.

A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells.

Hydrophobin-1 (HFB-1) found on the surface of fungal spores, plays a role in the lack of antigen recognition by the host immune system. The present study aimed to evaluate the potential application of HFB-1 for the delivery of doxorubicin (Dox) into different cell lines. Coating the surface of niosomes (Nio) with HFB-1 leads to the hypothesis that this protein can confer protection against in vivo immune-system recognition and prevent the immune response. Thus, HFB-1 could become a promising alternative to polyethylene glycol (PEG). Here, HFB-1-coated niosome loaded with doxorubicin (Dox) based on Span 40, Tween 40 and cholesterol was prepared and compared with the PEG-coated niosome. Physicochemical characteristics of the prepared formulations in terms of size, zeta potential, polydispersity index (PDI), morphology, entrapment efficiency (EE), and release rate were evaluated at different pH levels (2, 5.2, and 7.4). In the end, the in vitro cytotoxicity assay was performed on four different cancer cell lines namely A549, MDA-MB-231, C6 and PC12 in addition to one control cell line (3 T3) to ensure the formulation's selectivity against cancer cells. Results showed that the niosomes coated with HFB-1 presented better size distribution, higher EE, more sustained release profile, enhanced biocompatibility and improved anticancer effects as compared to the PEG-coated niosomes. Interestingly, the viability percentage of the control cell line was higher than different cancer cells when treated with the formulations, which indicates the higher selectivity of the formulation against cancer cells. In conclusion, loading the niosomes with Dox and coating them with HFB-1 enhanced their efficacy and selectivity toward cancer cells, presenting a promising drug delivery system for sustained drug release in cancer treatment.

Bimetallic nickel-ferrite nanorod particles: greener synthesis using rosemary and its biomedical efficiency.

Nickel-ferrite (NiFe2O4) nanorods particles (NRP) was biosynthesised for the first time by the Rosemary Extract. The NRP was fully characterised, including the type, nanostructure and physicochemical properties of using XRD, HRTEM, FeSEM, XPS, FTIR and VSM. TEM confirmed rod-shaped nano-sized particles with average sizes ranging from 10 nm to 28 nm. The EDAX Analysis showed the presence of iron, nickel, oxygen, and carbon. XRD analysis confirmed the synthesis of NiFe2O4 crystals. XPS curves showed photoelectron for iron, oxygen and nickel. EDS showed the atomic, weight percentages ratios of Ni(12%): Fe(24%) and: O(48) are close to the theoretical value (Ni: Fe:O = 1:2:4), of bimetallic magnetic NiFe2O4 NRP. NiFe2O4 NRP had cytotoxicity effect on MCF-7 cells survival which suggests that NiFe2O4 NRP can be used as a new class of anticancer agent in design novel cancer therapy research.

The Blepharis persica seed hydroalcoholic extract synergistically enhances the apoptotic effect of doxorubicin in human colon cancer and gastric cancer cells.

The goal of this survey is to evaluate the anti-proliferative effects of the hydroalcholic extract of Blepharis persica seeds and its synergic effect on doxorubicin (DOX) in human colon cancer (HT-29) and gastric cancer cell (AGS) lines. 70% Ethanol was used for extraction of B. persica seed. Aluminum-chloride colorimetric and Folin-Ciocalteu reagent methods were used to measure total flavonoid and total phenolic contents of the extract respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of the B. persica extract was performed on GC-MS equipment after silylation. HT-29, AGS, and human fibroblast (SKM) cell lines were treated by different concentration of the B. persica extract, (DOX) and the combination of extraction and DOX. The cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay while the apoptosis induction was monitored using flowcytometry by annexin-V FITC/PI double-staining. The changes in expression levels of BAX and BCL-2 were determined using Real-Time RT-qPCR. GC-MS analysis of the hydroalcoholic extract from B. persica seeds revealed 24 major components. The MTT assay revealed the cytotoxicity against three cell lines and also it was shown that 125 ng/mL of DOX and 0.625 mg/mL of B. persica extract had synergistic behavior against HT29 cell line. These results showed B. persica extract induced apoptosis in AGS and HT29 cells and its extract caused dose-dependent increase in up-regulation of BAX level (p < 0.05) and down-regulation of BCL2 (p < 0.05). B. persica showed the synergistic effect in combination with DOX on HT29 cell line. These findings demonstrated a basis for further studies on the characterization and mechanistic evaluation of the bioactive compounds of B. persica extract which had antiproliferative effects on cancer cell lines.

In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents.

The low solubility of the plant-extracted agent like D-limonene in cancer therapy is a critical problem. In this study, we prepared D-limonene-loaded niosomes (D-limonene/Nio) for cancer therapy through in vitro cytotoxicity assay of HepG2, MCF-7, and A549 cell lines. The niosomal formulation was prepared by film hydration technique with Span® 40: Tween® 40: cholesterol (35:35:30 molar ratio) and characterized for vesicle distribution size, morphology, entrapment efficiency (EE%), and in vitro release behaviour. The obtained niosomes showed a nanometric size and spherical morphology with EE% about 87 ± 1.8%. Remarkably prolonged release of D-limonene from niosomes compared to free D-limonene observed. The loaded formulation showed significantly enhanced cytotoxic activity with all three cancer cell lines (HepG2, Macf-7 and A549) at the concentration of 20 µM. These results indicated that niosome loaded with phytochemicals can be a promising nano-carrier for cancer therapy applications.

Evaluation of Carum-loaded Niosomes on Breast Cancer Cells:Physicochemical Properties, In Vitro Cytotoxicity, Flow Cytometric, DNA Fragmentation and Cell Migration Assay.

Thymoquinone (TQ), a phytochemical compound found in Carum carvil seeds (C. carvil), has a lot of applications in medical especially cancer therapy. However, TQ has a hydrophobic nature, and because of that, its solubility, permeability and its bioavailability in biological mediums are poor. To diminish these drawbacks, we have designed a herbal carrier composed of Ergosterol (herbal lipid), Carum carvil extract (Carum) and nonionic surfactants for herbal cancer treatment. C. carvil was extracted and characterized by GC/Mass. Two different formulations containing TQ and Carum were encapsulated into niosomes (Nio/TQ and Nio/Carum, respectively) and their properties were compared together. Morphology, size, zeta potential, encapsulation efficiency (EE%), profile release rate, in vitro cytotoxicity, flow cytometric, DNA fragmentation and cell migration assay of formulations were evaluated. Results show that both loaded formulations have a spherical morphology, nanometric size and negative zeta potential. EE% of TQ and Carum loaded niosomes was about 92.32% ± 2.32 and 86.25% ± 1.85, respectively. Both loaded formulations provided a controlled release compared with free TQ. MTT assay showed that loaded niosomes have more anti-cancer activity compared with Free TQ and free Carum against MCF-7 cancer cell line and these results were confirmed by flow cytometric analysis. Cell cycle analysis showed G2/M arrest in TQ, Nio/TQ and Nio/Carum formulations. TQ, Nio/TQ and Nio/Carum decreased the migration of MCF7 cells remarkedly. These results show that the TQ and Carum loaded niosomes are novel carriers with high efficiency for encapsulation of low soluble phytochemicals and also would be favourable systems for breast cancer treatment.

Diosgenin-loaded niosome as an effective phytochemical nanocarrier: physicochemical characterization, loading efficiency, and cytotoxicity assay.

BACKGROUND: The use of phytochemicals to prevent or suppress tumours is known as chemoprevention. Numerous plant-derived agents have been reported to have anticancer potentials. As one such anticancer phytochemical, diosgenin has several applications which are nevertheless limited due to its low solubility in water. METHODS: We loaded diosgenin into niosome to increase its solubility and hence efficiency. Diosgenin-niosome (diosgenin loaded into niosome) was prepared by thin-film hydration method and characterised by optical microscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV-visible spectrophotometry. Also, loading efficiency, in vitro drug release, and cytotoxicity assay were performed on HepG2 cell line. RESULTS AND DISCUSSION: Diosgenin-niosome has a nanometric size with a normal size distribution and spherical morphology. The loading efficiency of diosgenin was about 89% with a sustainable and controllable release rate. Finally, the viability of free diosgenin was 61.25%, and after loading into niosomes, it was improved to 28.32%. CONCLUSION: The results demonstrated that niosomes increase the solubility of naturally derived hydrophobic chemicals and thus enhance their anticancer effect. Graphical abstract.

Tris-chelated complexes of nickel(II) with bipyridine derivatives: DNA binding and cleavage, BSA binding, molecular docking, and cytotoxicity.

Two nickel(II) complexes with substituted bipyridine ligand of the type [Ni(NN)3](ClO4)2, where NN is 4,4'-dimethyl-2,2'-bipyridine (dimethylbpy) (1) and 4,4'-dimethoxy-2,2'-bipyridine (dimethoxybpy) (2), have been synthesized, characterized, and their interaction with DNA and bovine serum albumin (BSA) studied by different physical methods. X-ray crystal structure of 1 shows a six-coordinate complex in a distorted octahedral geometry. DNA-binding studies of 1 and 2 reveal that both complexes sit in DNA groove and then interact with neighboring nucleotides differently; 2 undergoes a partial intercalation. This is supported by molecular-docking studies, where hydrophobic interactions are apparent between 1 and DNA as compared to hydrogen bonding, hydrophobic, and π-π interactions between 2 and DNA minor groove. Moreover, the two complexes exhibit oxidative cleavage of supercoiled plasmid DNA in the presence of hydrogen peroxide as an activator in the order of 1 > 2. In terms of interaction with BSA, the results of spectroscopic methods and molecular docking show that 1 binds with BSA only via hydrophobic contacts while 2 interacts through hydrophobic and hydrogen bonding. It has been extensively demonstrated that the nature of the methyl- and methoxy-groups in ligands is a strong determinant of the bioactivity of nickel(II) complexes. This may justify the above differences in biomolecular interactions. In addition, the in vitro cytotoxicity of the complexes on human carcinoma cells lines (MCF-7, HT-29, and U-87) has been examined by MTT assay. According to our observations, 1 and 2 display cytotoxicity activity against selected cell lines. Communicated by Ramaswamy H. Sarma.

Synthesis and characterization of a novel organosilane-functionalized chitosan nanocarrier as an efficient gene delivery system: Expression of green fluorescent protein.

Semi-essential arginine amino acid was selected to synthesis an organosilane linker for modifying chitosan biopolymer. The novel organosilane linker which was chemically synthesized by reaction of arginine with 3­chloropropyl trimethoxy silane, covalently bonded to the chitosan amino group. The chemical structure of resulting nanocarrier was characterized by 1H NMR, wide-X-ray diffraction, TEM, FESEM and EDX. A maximum retardation capacity of the nanocarrier to the plox plasmid was obtained 3 at physiological pH (7.4). The mean of cell viability and cytotoxicity of the nanocarrier was determined 85% by MTT assay. In addition, the gene transfection of the nanocarrier was obtained top of 20% gene expression. The studies have shown very good DNase 1 enzyme protection of plasmid by the nanocarrier.

In vitro cytotoxicity studies of parent and nanoencapsulated Holmium-2,9-dimethyl-1,10-phenanthroline complex toward fish-salmon DNA-binding properties and antibacterial activity.

In this study, the interaction of Holmium (Ho) complex including 2, 9-dimethyl-1,10-phenanthroline, also called Neocuproine (Neo), [Ho(Neo)2Cl3.H2O], as fluorescence probe with fish-salmon DNA (FS-DNA) is studied during experimental investigations. Multi-spectroscopic methods are utilized to determine the affinity binding constants (Kb) of complex-FS-DNA. It is found that fluorescence of Ho complex is strongly quenched by the FS-DNA through a static quenching procedure. Under optimal conditions in Tris(trishydroxymethyl-aminomethane)-HCl buffer at 25 °C with pH ≈ 7.2, intrinsic binding constant Kb of Ho complex is 6.12 ± 0.04 × 105 M-1. Also, the binding site number and Stern-Volmer quenching constant are calculated. There are different approaches, including iodide quenching assay, salt effect and thermodynamical assessment to determine the features of the binding mode between Ho complex and FS-DNA. Also, the parent and starch and lipid nanoencapsulated Ho complex, as potent antitumor candidates, were synthesized. The main structure of Ho complex is maintained after encapsulation using starch and lipid nanoparticles. 3-[4,5-Dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method was used to assess the anticancer properties of Ho complex and its encapsulated forms on human cancer cell lines of human lung carcinoma cell line and breast cancer cell line. In conclusion, these compounds could be considered as new antitumor candidates. Communicated by Ramaswamy H. Sarma.

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.

Magnetic delivery of antitumor carboplatin by using PEGylated-Niosomes.

To improve the efficiency of niosomal drug delivery, here we employed two tactics. First, niosomes were magnetized using Fe3O4@SiO2 mangnetic nanoparticles, and second, their surface was modified by PEGylation. PEGylation was intended for increasing the bioavailability of niosomes, and magnetization was used for rendering them capable of targeting specific tissues. These PEGylated magnetic niosomes were also loaded with Carboplatin, an antitumor drug. Next, these niosomes were studied in terms of size, morphology, zeta potential, and drug entrapment efficiency. Then, the in vitro drug release from these modified niosomes was compared to that of both naked and nonmagnetized niosomes. Interestingly, although loading of naked-niosomes with magnetic particles lead to an increase in the rate of drug release, PEGylation of these magnetized niosomes caused a more sustained drug release. Thus, PEGylation of magnetic niosomes, besides improving their bioavailability, caused a slower and sustained release of the drug over time. Finally, studying the in vitro effectives of niosomal formulations towards MCF-7, a breast cancer cell line, showed that PEGylated magnetic niosomes had a satisfactory toxicity towards these cells in the presence of an external magnetic field. In conclusion, PEGylated magnetic niosomes showed enhanced qualities regarding the controlled release and delivery of drug. Graphical abstract ᅟ.