Human Epithelial Carcinoma Cell Line Research Articles

Design, synthesis, characterization, and in vitro cytotoxic activity evaluation of 1,2‐disubstituted benzimidazole compounds

AbstractA series of 2‐p‐tolyl‐1H‐benzo[d]imidazole derivatives were synthesized and characterized. For finding an effective anticancer drug, which could be used in future generations, the developed heterocyclic compounds were screened in the human epithelial breast adenocarcinoma cell line (MCF‐7) and human liver epithelial hepatocellular carcinoma cell line (HepG2) using the MTT assay method. Two positive control drugs were used for comparison with the compounds. The substituents on the 1‐ and 2‐positions of the benzimidazole core had an important effect on the antiproliferation of cancerous cells. According to the results obtained, a compound, namely, 1‐(4‐methylbenzyl)‐2‐p‐tolyl‐1H‐benzo[d]imidazole, which has electron donating groups (CH3) in the para position of a phenyl ring, showed higher cytotoxic activities compared to other compounds towards liver and breast cell lines. The compounds were found to have more cytotoxicity in HepG2 rather than MCF‐7.

HERBAL NANOSUSPENSION: IN VITRO CANCER STUDY AGAINST DIFFERENT CELL LINES

Herbal formulations marketed in India for many years providing its therapeutic benefits in health problems. Medicinal plants or their phytoconstituents are less toxic and free from side effects than synthetic drugs. However, formulation aspects of these phytoconstituents are limited due to its low solubility. Nanotechnology is a promising technique to increase the solubility of herbal drugs. This will lead to a subsequent reduction in drug dose. Nanoformulations such as nanosuspension increase the solubility of poorly soluble drugs and also have good targeting effects on different cells. The efficacy of herbal nanosuspensions evaluated using different cell lines. Here, hepatocellular carcinoma cell line (SMMC-7721), human prostate cancer cell line, human myelogenous leukemia cell line, human epithelial cell line, human breast cancer cell lines (4T1, MCF-7, and MDA-MB-453), carcinomic human alveolar basal epithelial cell line (A549), human umbilical vein endothelial cell line, human colorectal adenocarcinoma cell line (HT-29), and human epithelial carcinoma cell line (HeLa) are used in the evaluation procedures. In vitro assays help in the determination of the dose range of drugs for the activity. The present review highlights the in vitro cancer studies of herbal nanosuspensions using different cell lines.

MicroRNA-124-3p inhibits tumourigenesis by targeting mitogen-activated protein kinase 4 in papillary thyroid carcinoma.

The study aimed to investigate the role of miR-124-3p and its potential molecular mechanism in papillary thyroid cancer (PTC). The expression of miR-124-3p and mitogen-activated protein kinase 4 (MAP2K4) in human thyroid follicular epithelial cell line (NTHY-ORI3-1) and human papillary thyroid carcinoma cell lines (SW1736, BCPAP, TPC-1 and K1) was measured by RT-qPCR. Cell proliferation was measured by CCK-8, while cell cycle and apoptosis rate were measured by flow cytometry. Invasive ability and migrative ability were measured by transwell assay and wound healing assay, respectively. Western blot was used to detect the levels of relative proteins. In vivo, TPC-1 cells transfected with miR-124-3p mimic were subcutaneously injected into the flank of the mice to form tumour. After successful modelling, mice were divided into two groups (n = 10): Control group and miR-124-3p mimic group. The present study showed that miR-124-3p was lowly expressed, while MAP2K4 was highly expressed in PTC cell lines. Besides, miR-124-3p targeted MAP2K4 and negatively regulated MAP2K4 in TPC-1 cells. In addition, miR-124-3p inhibited the proliferation and motility, and induced apoptosis and cell cycle arrest of TPC-1 cells by inactivating MAP2K4/JNK/JunD pathway. Furthermore, miR-124-3p inhibited tumour formation by downregulating MAP2K4 level in vivo. In conclusion, the study provided a novel molecular mechanism of miR-124-3p in the progress of PTC. SIGNIFICANCE OF THE STUDY: Papillary thyroid cancer (PTC) is the most important pathological type of thyroid cancer, accounting for 80% of thyroid cancer. miR-124-3p exhibited significant inhibitory role in the transformation and development of malignant tumours. However, in PTC, the roles and its potential molecular mechanism are unclear. Here, the study investigated the roles of miR-124-3p in the progress of PTC and its potential molecular mechanism. We found that miR-124-3p inhibited the proliferation and motility, and induced apoptosis and cell cycle arrest in PTC cells. This study provided a novel molecular mechanism of miR-124-3p in the progress of PTC.

Effects of Microstripe Geometry on Guided Cell Migration

Cell migration on material surfaces is a fundament issue in the fields of biomaterials, cell biology, tissue engineering, regenerative medicine, etc. Herein, we aim to guide cell migration by flat microstripes with significant contrast of cell adhesion and varied geometric features of the adhesive stripes. To this end, we designed and fabricated cell-adhesive arginine-glycine-aspartate (RGD) microstripes on the nonfouling poly(ethylene glycol) (PEG) background and examined the microstripe-guided adhesion and migration of a few cell types. The migration of cell clusters adhering on the RGD regions was found to be significantly affected by the widths and arc radiuses of the guided microstripes. The cells migrated fastest on the straight microstripes with width of about 20 μm, which we defined as single file confined migration (SFCM). We also checked the possible left-right asymmetric bias of cell migration guided by combinatory microstripes with alternative wavy and quasi-straight stripes under a given width, and found that the velocity of CCW (counter clockwise) migration was higher than that of CW (clockwise) migration for primary rat mesenchymal stem cells (rMSCs), whereas no left-right asymmetric bias was observed for NIH3T3 (mouse embryonic fibroblast cell line) and Hela (human cervix epithelial carcinoma cell line) cells. Comparison of migration of cells on the nanotopological stripe and smooth surfaces further confirmed the importance of cell orientation coherence for guided cell migration and strengthened the superiority of SFCM.

Synthesis, crystallographic studies, electrochemical and in vitro cytotoxicity properties of two Mn‌(II) and U(IV) complexes containing dipicolinic acid and 4-dimethylaminopyridine

Two new coordination complexes, [pydcH2][Mn2(pydc)2(H2O)6] (1) and [dmapH2][UO2(pydc)2] (2) were obtained from a compound containing dipicolinic acid and 4-dimethylaminopyridine.The complexes were characterized by X-ray crystallography. Electrochemical behavior of the compounds was investigated by cyclic voltammograms. Redox couples were observed at E0ˊ 1.625 and –0.159 V for (1) and (2) respectively, versus Ag/AgCl, under argon. After aeration, stronger interaction tendency with oxygen was exhibited for complex (1) compared to (2), within 5 min. In the next section, toxicity of each of three compounds were assayed using oxaliplatin as a standard, under MTT method, against MCF7 (a human breast cancer), HeLa (a human cervix epithelioid carcinoma) and KB (a human oral epithelial carcinoma) cell lines. Complex (1) with E0ˊ of about ten times (2) proved further cytotoxic potential on all three tested cancerous cell line compared to (2). The highest inhibition potential was exhibited on MCF7 cell line (IC50 = 1.00 μM, Viability inhibition = 81.19%) for (1). Determination of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) in treated MCF7 cells with (1) confirmed a clear decrease in MMP and sharp increases in ROS generation in this cell line.

Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line

In this study, a new compound namely 1-((2-hydroxynaphthalen-1-yl)methyleneamino)-5-(4-methybenzoyl)-4-p-tolylpyrimidin-2(1H)-one (S2) was synthesized as a Schiff base using 1-amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidin-2(1H)-one (S1) with 2-hydroxy-1-naphthaldehyde in 80% yield. Then, eight novel metal complexes (S3–S10) including Ni(II), Cu(II), Co(II), Ag(I), Pd(II), Pt(II), Cr(III), and Mn(II) metal ions were prepared from this new Schiff base (S2). The characterization of these complexes was done using 1H NMR, 13C NMR, LC-MS, IR, magnetic susceptibility and conductivity measurements. The anticancer activities of compounds (S3–S10) were tested against human epithelial lung carcinoma cell line (A549) for 72 h. All complexes demonstrated antiproliferative activity in A549 cell line and low half-maximal inhibitory concentration (IC50) values were calculated with GraphPad Prism program.

Manganese-doped green tea-derived carbon quantum dots as a targeted dual imaging and photodynamic therapy platform.

In this work, manganese-doped carbon quantum dots (Mn-CQDs) have been synthesized through a one-pot hydrothermal method by using waste green tea. The Mn2+ dopants were introduced to impart magnetic resonance capability. Upon optimization of the experimental conditions, magnetofluorescent Mn-CQDs exhibit an excitation-dependent blue emission. The abundant functional groups on Mn-CQDs not only promote water solubility but also allow straightforward functionalization with amine groups. The amine-terminated Mn-CQDs were then subsequently conjugated to folic acid (FA) and chlorin e6 (Ce6) to obtain the Mn-CQDs@FA/Ce6 magnetofluorescent photodynamic therapy (PDT) agent. in vitro studies using three different cells indicated specific targeting of Mn-CQDs@FA/Ce6 to the overexpressing folate receptor human epithelial carcinoma cell line (HeLa) cancer cells. Furthermore, Mn-CQDs@FA/Ce6 enhanced magnetic resonance imaging (MRI) signal with an r2 /r1 ratio of 5.77. Favorably, by using the Mn-CQDs@FA delivery system, active Ce6 can reach the cellular interior while its red fluorescence (FL) and reactive oxygen species generation can be retained, as has been verified by confocal microscopy. in vitro cell viability studies verified the biocompatibility of Mn-CQDs@FA/Ce6 nanohybrid with no significant toxicity up to 500 ppm while PDT treatment with 5 min irradiation (671 nm, 1 W cm-2 ) was effective in killing >90% of cells. The light-triggered Mn-CQDs@FA/Ce6 multifunctional hybrid can serve as a dual-modal FL/MRI probe and as an efficient PDT agent to detect and eradicate cancer cells remotely.

Polystyrene Nanoparticles Induce Apoptosis or Necrosis With or Without Epidermal Growth Factor

Polystyrene nanoparticles (PS NPs) are biocompatible and low toxic material to biological systems. In this mind, PS NPs are widely used as a model for studying the interaction between nanoparticles and cells. Even PS NPs showed low toxicity, they could affect to some cellular responses. In this study, we investigated the influence of PS NPs on the epidermal growth factor (EGF)-response in the A431 human epithelial carcinoma cell line. The results showed that PS NPs interfered with the normal EGF-response of A431 cells in a dose-dependent manner. In addition, EGF significantly increased the uptake of PS NPs in A431 cells. Localization studies of PS NPs and EGF receptor (EGFR) indicated that changes in the EGF-response of A431 cells are related to the interaction between PS NPs and the EGF-EGFR complexes. The viability of cells exposed to PS NPs or combination of PS NPs and EGF decreased due to PS NPs induced cell death. The results also suggested that without EGF, PS NPs internalized in the cells cause cell death by necrosis, whereas EGF enhances the uptake ratio of PS NPs, and PS NPs in the cytoplasm together with EGF-EGFR complexes may inhibit receptors recycling, leading to apoptosis. This finding could be useful for the safe and effective use of nanoparticles in clinical applications.

Biofabrication of iron oxide nanoparticles as a potential photocatalyst for dye degradation with antimicrobial activity

In the current investigation presented here, avocado fruit rind aqueous extract was exploited to make iron oxide nanoparticles, in a cost competent and eco-cordial method. The Fourier transform infrared analysis exhibited that the phytochemicals which were in the avocado fruit rind acted as biodegradable, stabilizing and reducing agents in the iron oxide nanoparticles biofabrication. The nanoparticles were also tested for their role as a photocatalyst in the decolorization of selective dyes, using a dosage of 20 mg of iron oxide nanoparticles per 50 mL of dye exposed for 5-h sunlight irradiation. The color removal percentage was checked to be at 97, 93, 91, 89 and 82 for the dyes malachite green, Congo red, crystal violet, safranin and methyl orange, respectively. Iron oxide nanoparticles were appraised for their antibacterial response against the scrupulous choice of gram-negative and gram-positive bacteria through agar well diffusion technique. The zone of inhibition was ascertained to be 13, 12, 15, 11, 9, 12 and 14 mm for Escherichia coli, Streptococcus sp., Staphylococcus sp., Salmonella sp., Bacillus sp., Pseudomonas sp. and Proteus sp., respectively, with the aid of 20 µg mL−1 iron oxide nanoparticles. In vitro cytotoxicity of the iron oxide nanoparticles was evaluated on a human cervix epithelial carcinoma cell line, and their inhibitory concentration 50 value was deduced as 381.14 ± 10 µg mL−1. The result serves an allusion data, endorsing the avocado fruit rind sourced iron oxide nanoparticles as relevant agents in applications pertaining to environmental remediation.

Derivatives of 1‐(2‐(Piperidin‐1‐yl)ethyl)‐1H‐benzo[d]imidazole: Synthesis, Characterization, Determining of Electronic Properties and Cytotoxicity Studies

AbstractA series of heterocyclic compounds were synthesized and fully characterized. The geometry optimization was carried out using the Density Functional Theory (DFT) method and the electronic properties of 1‐(2‐hydroxyethyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl chloride)‐1H‐benzo[d]imidazol‐3‐ium bromide and 1‐(2‐methylbenzyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium dichloride were calculated. Furthermore, the all compounds were evaluated for their potential anticancer activity towards different human cell lines. While 1‐(naphthalen‐1‐ylmethyl)‐3‐(2‐(piperidin‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium chloride possessing naphthalen‐1‐ylmethyl group as substituent demonstrated important cytotoxic activity against human colorectal adenocarcinoma epithelial colon cell line (DLD‐1) with an IC50 value of 15.56 ± 4.01 μM, compound containing 4‐methylbenzyl group showed the most anticancer activity towards human liver epithelial hepatocellular carcinoma cell line (HepG2) with IC50 value of 15.16 μM. Moreover, microscopic examination of cells was done using Leica inverted microscopy and Olympus confocal microscope. Confocal images of DLD‐1 and human normal epithelial virus transformed cell line (Beas‐2B), which were treated with 20 μM of compounds, indicated that compounds 1‐(4‐methylbenzyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium dichloride and 1‐(naphthalen‐1‐ylmethyl)‐3‐(2‐(piperidin‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium chloride had more cytotoxic activity.

Chemical constituents of the lichen Dendriscosticta platyphylloides, Lobariaceae

Introduction: Dendriscosticta is a new genus belong the Sticta wrightii group of the family Lobariaceae. This genus of foliose lichen is widely distributed in tropical regions worldwide. The lichen Dendriscosticta platyphylloides is very abundant in Bidoup forest, Lam Dong province, Vietnam.
 Methods: The structure of these compounds was elucidated through the interpretation of their 1D and 2D-NMR and HR-MS data. The cytotoxic activities of these compounds against liver hepatocellular carcinoma (HepG2), human lung cancer (NCI-H460), human epithelial carcinoma (HeLa) and human breast cancer (MCF-7) cell lines was performed at the concentration of 100 mg/mL using the sulforhodamine B (SRB) assay.
 Results: In this paper, we reported the isolation of six known compounds, including (1) 15a-acetoxyhopan-22-ol (2) hopane-15a,22-diol, (3) zeorin, (4) cerevisterol, (5) salvigenin, and (6) 5-hydroxy-3',4',7-trimethoxyflavone.
 Conclusion: This is the first time that these compounds are isolated from Dendriscosticta genus. These compounds showed no cytotoxic activity against four cell lines.

Synthesis and anticancer activity of chalcone analogues with sulfonyl groups

Three series of sulfonyl esters were synthesized in reactions of sulfonyl chlorides with three different phenolic chalcone analogues (dehydrozingerone (4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one), (E)-1-(4-hydroxy-3-methoxyphenyl)pent-1-en-3-one, and (E)-1-(4-hydroxy-3-methoxyphenyl)-5-methylhex-1-en-3-one). The structures of the new compounds were determined by IR, MS, and NMR methods. Screening of the new sulfonyl esters’ in vitro cytotoxic activities against human epithelial cervical carcinoma (HeLa) and normal human fibroblast (MRC-5) cell lines by the MTT method was performed. The five most active were selected and further tested on HeLa, MRC-5, and MCF-7 (breast carcinoma) cell lines. The examined compounds exhibit strong in vitro anticancer activities with moderate-to-high selectivity, inducing apoptotic cell death and cell cycle arrest in both HeLa and MCF-7 cell lines, but have little to no effect on the non-cancerous MRC-5 cell line.

Targeted Suppression and Knockout of ASCT2 or LAT1 in Epithelial and Mesenchymal Human Liver Cancer Cells Fail to Inhibit Growth.

Amino acid transporters alanine-serine-cysteine transporter 2 (ASCT2) and L-Type Amino Acid Transporter 1 (LAT1) are coordinately enhanced in human cancers where among other roles, they are thought to drive mechanistic target-of-rapamycin (mTOR) growth signaling. To assess ASCT2 and LAT1 as therapeutic targets, nine unique short hairpin RNA (shRNA) vectors were used to stably suppress transporter expression in human epithelial (Hep3B) and mesenchymal (SK-Hep1) hepatocellular carcinoma (HCC) cell lines. In addition, six unique CRISPR-Cas9 vectors were used to edit the ASCT2 (SLC1A5) and LAT1 (SLC7A5) genes in epithelial (HUH7) and mesenchymal (SK-Hep1) HCC cells. Both approaches successfully diminished glutamine (ASCT2) and leucine (LAT1) initial-rate transport proportional to transporter protein suppression. In spite of profoundly reduced glutamine or leucine transport (up to 90%), transporter suppression or knockout failed to substantially affect cellular proliferation or basal and amino acid-stimulated mTORC1 growth signaling in either HCC cell type. Only LAT1 knockout in HUH7 slightly reduced growth rate. However, intracellular accumulation of radiolabeled glutamine and leucine over longer time periods largely recovered to control levels in ASCT2 and LAT1 knockout cells, respectively, which partially explains the lack of an impaired growth phenotype. These data collectively establish that in an in vitro context, human epithelial and mesenchymal HCC cell lines adapt to ASCT2 or LAT1 knockout. These results comport with an emerging model of amino acid exchangers like ASCT2 and LAT1 as “harmonizers”, not drivers, of amino acid accumulation and signaling, despite their long-established dominant role in initial-rate amino acid transport.

Regulation and biological role of the peptide/histidine transporter SLC15A3 in Toll-like receptor-mediated inflammatory responses in macrophage

The peptide/histidine transporter SLC15A3 is responsible for transporting histidine, certain dipeptide and peptidomimetics from inside the lysosome to cytosol. Previous studies have indicated that SLC15A3 transcripts are mainly expressed in the lymphatic system, however, its regulation and biological role in innate immune responses and inflammatory diseases are as yet unknown. In this study, mouse peritoneal macrophages (PMs), mouse bone marrow-derived macrophages (BMDMs), the human acute monocytic leukemia cell line THP-1 and the human lung epithelial carcinoma cell line A549 were used to investigate the regulation and biological role of SLC15A3 in TLR-mediated inflammatory responses. Our results showed that SLC15A3 was upregulated by TLR2, TLR4, TLR7 and TLR9 ligands in macrophages at both the mRNA and protein levels via activation of NF-κB (nuclear factor-kappa-B), MAPK (mitogen-activated protein kinase) and IRF3 (interferon regulatory factor 3). Furthermore, knockdown or overexpression of SLC15A3 influenced the TLR4-triggered expression of proinflammatory cytokines. A reporter gene assay showed that the SLC15A3 promotor contained potential NF-κB binding sites, which were reasonable for regulating SLC15A3 by TLR-activation through NF-κB signaling. Additionally, SLC15A3 expression was increased and positively related to inflammation in mice with bacterial peritonitis. The collective findings suggest that SLC15A3 is regulated by various TLRs, and that it plays an important role in regulating TLR4-mediated inflammatory responses.

SOME TRITERPENOIDS AND STEROIDS FROM THE LICHEN LOBARIA ORIENTALIS, LOBARIACEAE.

Chemical investigation of the ethyl acetate extract of the lichen Lobaria orientalis,Lobariaceae, collected in Vietnam, afforded six known compounds, including four triterpenoids,zeorin (1), 16β-acetoxyhopane-6α,22-diol (2), retigeric acid A (3), retigeric acid B (4), togetherwith two steroids, ergosterol-5α,8α-peroxide (5) and cerevisterol (6). Their chemical structureswere elucidated by spectroscopic data analysis and comparison with those reported in theliterature. The cytotoxic activities of some compounds against liver hepatocellular carcinoma(HepG2), human lung cancer (NCI-H460), human epithelial carcinoma (HeLa) and humanbreast cancer (MCF-7) cell lines were evaluated. Compound 2 exhibited good cytotoxicityagainst MCF-7 cancer cell line with IC50 value of 21.10 μg/mL. This is the first time compounds(1), (2), (6) are reported in the Lobaria genus.

Chemical composition and antiproliferative potential of dried wild apple and pear tea before and after in vitro simulated digestion

Decoctions obtained from dried apple and pear fruits were subjected to in vitro digestion in the presence of a food matrix in order to determine changes in the polyphenol content and antiproliferative activity. The total phenolic and total proanthocyanidins contents were determined using spectrophotometrical methods, and the phenolic compounds were analyzed by RP-HPLC/DAD before and after digestion. Chlorogenic acid and phlorizin dihydrate were the major identified compounds. The addition of a food matrix immediately decreased the contents of individual and total phenolics. After digestion, they were slightly elevated but still lower than in the initial samples. Antiproliferative activity was investigated on human epithelial carcinoma cell line (HeLa), human colon carcinoma (LS174) and human foetal lung fibroblast (MRC-5) cells. The exhibited growth inhibition was not correlated with the content of phenolics in the tested samples, indicating that it could not be explained solely by their content. With the exception of the apple decoction effect on HeLa cells, the digestion process resulted in significant increases in the antiproliferative activity.

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment.

Novel liposome-based and in situ gelling artificial tear formulation for dry eye disease treatment.

Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200-1000 s-1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.

An in vitro cytotoxicity assessment of graphene nanosheets on alveolar cells

The collection of intrinsic properties possessed by graphene family nanomaterials (GFNs) results in their continuous exploitation for biomedical applications. The materials biomedical potential has motivated an upsurge in green preparation routes for the production of graphene like materials with limited toxicity. A number of bio-friendly reducing agents have been utilized for the preparation of chemically reduced graphene oxide (GO), and their resulting cytotoxic effects examined. However, the toxicology effects of one of the first biomolecules implemented for the reduction of GO, ascorbic acid (AA) has yet to be investigated. Herein, the toxicity of three distinct GFNs; GO, hydrazine reduced GO (H.rGO) and AA.rGO, prepared through diverse chemical routes are studied, to demonstrate the cytotoxic activity of a green reducer, in comparison to an established reduction method using hydrazine hydrate. The variation in atomic structure of GO, H.rGO and AA.rGO resulting from different synthesis techniques demonstrates the dependence of toxicity on particle shape and size. All GFNs induced high levels of alveolar cell toxicity. Interaction of AA.rGO with the A549 human lung epithelial carcinoma cell line resulted in increased leakage of lactate dehydrogenase, indicative of diminished cell membrane integrity. The uncharacteristic shape of the AA.rGO may be responsible for this proliferated release of the essential protein. The presented data therefore demonstrates that modification of synthetic processes significantly alter the biological activities of GFNs.

Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

Monastrol is a simple low molecular weight dihydropyrimidine-based kinesin Eg5 inhibitor. Its low cellular activity and its non-drug-like properties have impeded its further development. In a previous report, we have reported various topological parameters to improve the pharmacokinetic properties of monastrol. The purpose of this study is to determine the loading and release feasibility of poorly water-soluble monastrol into the synthesized mesoporous silica nanoparticles (MSNs). The synthesis of MSNs was attained by the ammonia-catalysed hydrolysis and condensation of TEOS in ethanol using polysorbate-80 as surfactant. These were characterized by BET surface area and pore size distribution analyses, SEM, XRD, UV and FTIR spectroscopy. The synthesized monastrol was successfully loaded on MSNPs and coated by hydrogels for successful controlled drug delivery. In vitro release studies are done by simple dialysis method. Monastrol-loaded MSNPs were tested on human cervical epithelial malignant carcinoma (HeLa) cell lines for studying their anticancer activity. Our presented system described a reliable method for targeted delivery of monastrol into the cancer cells in vitro.