marziyeh hajialyani
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This study, for the first time, tries to provide a simultaneous experimental and computational fluid dynamic (CFD) simulation investigation for production of uniform, reproducible, and stable polylactic-co-glycolic acid (PLGA) nanoparticles. CFD simulation was carried out to observe fluid flow behavior and micromixing in microfluidic system and improve our understanding about the governing fluid profile. The major objective of such effort was to provide a carrier for controlled and sustained release profile of different drugs. Different experimental parameters were optimized to obtain PLGA nanoparticles with proper size and minimized polydispersity index. The particle size, polydispersity, morphology, and stability of nanoparticles were compared. Microfluidic system provided a platform to control over the characteristics of nanoparticles. Using microfluidic system, the obtained particles were more uniform and harmonious in size, more stable, monodisperse and spherical, while particles produced by batch method were non-spherical and polydisperse. The best size and polydispersity index in the microfluidic method was obtained using 2% PLGA and 0.0625% (w/v) polyvinyl alcohol (PVA) solutions, and the flow rate ratio of 10:0.6 for PVA and PLGA solutions. CFD simulation demonstrated the high mixing intensity of about 0.99 at optimum condition in the microfluidic system, which is the possible reason for advantageous performance of this system. Altogether, the results of microfluidic-assisted method were found to be more reproducible, predictable, and controllable than batch method for producing a nanoformulation for delivery of drugs.
Keywords: Computational fluid dynamic, Microfluidics, Nanoparticles, Nanoprecipitation, Polylactic-coglycolicacid -
PurposesIn the present study, we tried for the first time to examine the anti-proliferative andanti-apoptogenic effect of Glabridin (Glab) toward three groups of cancer cells (SKNMC,H1299, and A2780). Furthermore, the possibility of co-administration of Glab with doxorubicin(DOX) to these cells was also examined to find out whether Glab can potentiate the cytotoxiceffect of this chemotherapy agent.MethodsDifferent cellular assays (MTT, caspase-3 activity, MMP, RT-PCR analysis) were carriedout on the cancer cells treated with Glab.ResultsCellular toxicity assay revealed that Glab can potentially reduce the viability of thesecells with IC50 concentrations up to 10, 12, and 38 μM toward A2780, SKNMC, and H1299 celllines, respectively. The results of MMP and caspase-3 activity assays, in association with theresults corresponding to the BAX and Bcl-2 gene expressions, altogether revealed that Glab canexert apoptogenic effect on these cells. The intrinsic mitochondrial pathway was found to bethe main mechanism, in which Glab induced apoptosis toward H1299 cells and SKNMC cells,while the apoptosis mechanism for A2780 cells could be probably through extrinsic pathway.Glab also potentiated the cytotoxic effect of DOX and its accumulation in H1299 cell line.ConclusionThe results of this study revealed the promising cytotoxic role of Glab on differentcarcinoma cells. These data also suggested that co-chemotherapy method using Glab could beeffective for treatment of cancer, but further in-vivo and clinical studies are still needed to assurethese results.Keywords: Apoptosis, Cytotoxicity, Doxorubicin, Glabridin, Herbal medicine, Licorice
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This study evaluated the anti-atherosclerosis effect of aqueous extract and polysaccharide-enriched fraction of Prosopis farcta on adhesion and inflammatory cascades in vascular endothelial cells and related molecular mechanisms. Cellular toxicities of LPS, plant extract and polysaccharide-enriched fraction were analyzed in vitro using the MTT method. The ROS accumulation, mRNA expression of ICAM1 and VCAM1, and COX activity were measured in HUVEC cells. These results revealed a new underlying mechanism for anti-atherosclerosis effect of P. farcta and polysaccharide-enriched fraction by attenuating inflammatory cascade mediated by COX expression, modulating expression of cell-adhesion molecules including VCAM-1 and ICAM-1, and diminishing oxidative stress agents.Keywords: Atherosclerosis, Cytotoxicity, HUVEC, LPS, Prosopis Farcta, Adhesion Mole cules
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The antiproliferative effect of dichloromethane extract of Artemisia aucheri (A. aucheri) has been demonstrated previously on human cancerous cell lines. In the current study, further fractionation was carried out on the dichloromethane extract of A. aucheri and their cytotoxic effects were evaluated on three human cancer cell lines; SKNMC, MCF-7, and A2780. Cell viability was determined by MTT assay and activation of caspases was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the genes expression. Detection of DNA fragmentation was carried out by flow cytometry. The obtained results showed that fractions 5 and 7 (F5 and F7) have a potent cytotoxic effect, especially against MCF-7 cells. F5 and F7 also induced apoptosis through the DNA fragmentation and mitochondrial membrane potential (MMP) disruption in MCF-7 cells. The caspase-3, 9 enzyme activities were also increased after exposure to F5 and F7. Moreover, caspase-8 activity increased significantly after exposure to F7 but not F5. The level of mRNA expressions of Bax and Smac/DIABLO was increased after exposure to both fractions. A detectable decrease was also observed in the mRNA expression of Bcl-2 after exposure to F7. No change was observed in the level of mRNA expressions of tumor suppressor P53 after exposure to F7. Therefore, the cell cycle arrest and apoptosis induced by F7 could probably be mediated through a p53-independent mechanism. Taken together, these observations demonstrated that the cytotoxic effect of F5 and F7 on MCF-7 cells is likely exerted via apoptotic cell death.Keywords: Artemisia aucheri, Fractions, Apoptosis, MCF-7 cells, SKNMC cells, A2780 cells
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PurposeThis paper introduces a green and simple hydrothermal synthesis to prepare carbon quantum dots (CQDs) from walnut oil with a high quantum yield. In addition, cytotoxic and apoptogenic properties of the CQDs were analyzed on human cancer cell lines.MethodsThe optical properties and morphological characteristic were investigated by the TEM, XRD, FT-IR, UV-vis and photoluminescence (PL).The cytotoxic potential of walnut CQDs was evaluated on PC3, MCF-7 and HT-29 human carcinoma cell lines using the MTT methods. The mechanism of action was studied by investigating the mode of cell death using the activation of caspase-3 and 9 as well as mitochondrial membrane potential (MMP). Cellular uptake of the CQDs was detected by fluorescence microscope. CQDs had an average size of 12 nm and a significant emission at 420 nm at an excitation wavelength of 350 nm was recorded.ResultsThe prepared CQDs possessed a good fluorescent quantum yield of 14.5% with quinine sulfate (quantum yield 54%) as a reference and excellent photo as well as pH stabilities. The walnut CQDs were proved to be an extremely potent cytotoxic agent, especially against MCF-7 and PC-3 cell lines. Induction of apoptosis by CQDs was accompanied by an increase in the activation of caspase-3. Caspase-9 activity did not increase after exposure to the CQDs. Additionally; the MMP did not show any significant loss.ConclusionThe results of our study can corroborate the cytotoxic and apoptotic effect of walnut CQDs in the PC3 and MCF-7 cancer cell lines.Keywords: Apoptogenic Activity, Carbon Quantum Dots, Human Carcinoma Cell Lines, Walnut Oil
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In order to achieve the controlled release of all-trans-retinoic acid (ATRA), poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) copolymer with average molecular weight of 5.34 kDa was synthesized. The nanosized micelles were prepared from copolymer by nano-precipitation method. Critical association concentration (CAC) of micelles was measured by fluorimetry and results indicated low CAC value of micelles (1.9 × 10-3 g/L). ATRA was encapsulated in the core of micelles using different ratios of drug to copolymer. In the case of 10% drug to polymer ratio, more than 80% of the drug was released within 3 days, whereas for ratio of 2% more than 90% of the drug was released within 3 h. The cytotoxic study performed by MTT assay showed that H1299 survival percent decreased significantly (P ≤ 0.05) after exposure to drug-loaded micelles, while no proliferation inhibition effect was observed by either free ATRA or blank PCL-PEG-PCL micelles.Keywords: Poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone), Micelle, All trans retinoic acid (ATRA), H1299, Cytotoxicity
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PurposeThis study aims to prepare a novel, natural nanoparticle (NP) as a drug carrier, which also has inherent therapeutic effects.MethodsPistacia khinjuk gum NPs were prepared and Response surface methodology (RSM) was used for statistical analysis of data and optimizing the size of NPs.ResultsNPs were in the range of 75.85241.3 nm. The optimization study was carried out, and an optimized size (70.86nm) was obtained using DMSO as a solvent. The volume of the organic phase was 111.25μl, and the concentration of gum was 1% w/v. The cell viability assay was performed on the pure gum and NPs toward β-TC3, MCF7, and HT29 cell lines. It was observed that NPs have higher cytotoxic activity in comparison with pure gum, and that the IC50value was achieved at 1% of NPs in β-TC3 cells. The obtained NPs demonstrated antibacterial activity against two bacterial strains (Pseudomonas aeruginosa and Staphylococcus aureus).ConclusionAltogether, according to the obtained results, these NPs with inherent cytotoxicity and antibacterial activity are an attractive carrier for drug delivery.Keywords: Antibacterial activity, Cytotoxicity, Nanoparticle, Pistacia Khinjuk, Response Surface Model
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