LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.).

Science.gov (United States)

Chen, Zijing; Zhao, Wensheng; Ge, Danfeng; Han, Yingyan; Ning, Kang; Luo, Chen; Wang, Shenglin; Liu, Renyi; Zhang, Xiaolan; Wang, Qian

2018-05-17

Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis. Molecular biology, developmental biology, and biochemical tools were combined to investigate the biological function of LsSOC1 in lettuce. LsSOC1 knockdown by RNA interference resulted in a significant delay in the timing of bolting and insensitivity to high temperature, which indicated that LsSOC1 functions as an activator during heat-promoted bolting in lettuce. We determined that two heat-shock transcription factors, HsfA1e and HsfA4c, bound to the promoter of LsSOC1 to confirm that LsSOC1 played an important role in heat-promoted bolting. This study indicates that LsSOC1 plays a crucial role in the heat-promoted bolting process in lettuce. Further investigation of LsSOC1 may be useful for clarification of the bolting mechanism in lettuce. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Transtuzumab-conjugated liposome-coated fluorscent magnetic namoparticles to target breast cancer

Energy Technology Data Exchange (ETDEWEB)

Jang, Mi Jung; Lee, Hak Jong; Hwang, Sung Il; Yun, Bo La; Kim, Sun Mi [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Yoon, Young Il; Kwon, Yong Soo [Nanoimaging and Therapy Research Center, Institute of Nanoconvergence, Advanced Institutes of Convergence Technology, Seoul National University, Suwon (Korea, Republic of); Yoon, Tae Jong [NanoBio Materials Chemistry Lab., Dept. of Applied Bioscience, CHA University, Pocheon (Korea, Republic of)

2014-08-15

To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNPm-SiO{sub 2}]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNPm-SiO{sub 2}]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. The physiochemical characteristics of Lipo[MNPm-SiO{sub 2}] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNPm-SiO{sub 2}] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin)-conjugated Lipo[MNPm-SiO{sub 2}] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. We obtained uniformly-sized and evenly distributed Lipo[MNPm-SiO{sub 2}] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] was observed by in vitro fluorescence and MR imaging. Trastuzumab-conjugated Lipo[MNPm-SiO{sub 2}] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

Monoclonal antibody against recombinant Fasciola gigantica cathepsin L1H could detect juvenile and adult cathepsin Ls of Fasciola gigantica.

Science.gov (United States)

Wongwairot, Sirima; Kueakhai, Pornanan; Changklungmoa, Narin; Jaikua, Wipaphorn; Sansri, Veerawat; Meemon, Krai; Songkoomkrong, Sineenart; Riengrojpitak, Suda; Sobhon, Prasert

2015-01-01

Cathepsin Ls (CatLs), the major cysteine protease secreted by Fasciola spp., are important for parasite digestion and tissue invasion. Fasciola gigantica cathepsin L1H (FgCatL1H) is the isotype expressed in the early stages for migration and invasion. In the present study, a monoclonal antibody (MoAb) against recombinant F. gigantica cathepsin L1H (rFgCatL1H) was produced by hybridoma technique using spleen cells from BALB/c mice immunized with recombinant proFgCatL1H (rproFgCatL1H). This MoAb is an immunoglobulin (Ig)G1 with κ light chain isotype. The MoAb reacted specifically with rproFgCatL1H, the native FgCatL1H at a molecular weight (MW) 38 to 48 kDa in the extract of whole body (WB) of metacercariae and newly excysted juvenile (NEJ) and cross-reacted with rFgCatL1 and native FgCatLs at MW 25 to 28 kDa in WB of 2- and 4-week-old juveniles, adult, and adult excretory-secretory (ES) fractions by immunoblotting and indirect ELISA. It did not cross-react with antigens in WB fractions from other parasites, including Gigantocotyle explanatum, Paramphistomum cervi, Gastrothylax crumenifer, Eurytrema pancreaticum, Setaria labiato-papillosa, and Fischoederius cobboldi. By immunolocalization, MoAb against rFgCatL1H reacted with the native protein in the gut of metacercariae and NEJ and also cross-reacted with CatL1 in 2- and 4-week-old juveniles and adult F. gigantica. Therefore, FgCatL1H and its MoAb may be used for immunodiagnosis of both early and late fasciolosis in ruminants and humans.

Internal radiotherapy and dosimetric study for {sup 111}In/{sup 177}Lu-pegylated liposomes conjugates in tumor-bearing mice

Energy Technology Data Exchange (ETDEWEB)

Wang, H.-E. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Yu, H.-M. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lu, Y.-C. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Heish, N.-N. [National Health Research Institute, Taipei, Taiwan (China); Tseng, Yun-Long [Taiwan Liposome Co. Ltd., Taipei, Taiwan (China); Huang, K.-L. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chuang, K.-T. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, Chin-Hsiung [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Hwang, J.-J. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lin, W.-J. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Wang, Shyh-Jen [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Ting, G. [National Health Research Institute, Taipei, Taiwan (China); Whang-Peng, Jacqueline [National Health Research Institute, Taipei, Taiwan (China); Deng, W.-P. [Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan (China)]. E-mail: wpdeng@tmu.edu.tw

2006-12-20

In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with {sup 111}In/{sup 177}Lu-(oxine){sub 3} to afford {sup 111}In/{sup 177}Lu-liposome. The stability of {sup 111}In/{sup 177}Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of {sup 111}In/{sup 177}Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of {sup 111}In/{sup 177}Lu into liposomes was 95%. After incubation at 37 {sup o}C for 72 h in serum, more than 83% of radioactivity was still retained in the intact {sup 111}In/{sup 177}Lu-liposomes. The biodistribution of {sup 111}In-liposomes showed that the radioactivity in the blood decreased from 23.14{+-}8.16%ID/g at 1 h to 0.02{+-}0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of {sup 177}Lu-liposomes. Scintigraphic imaging with {sup 111}In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from {sup 177}Lu-liposomes was 5.74x10{sup -5} Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

Global Convergence of a Modified LS Method

Directory of Open Access Journals (Sweden)

Liu JinKui

2012-01-01

Full Text Available The LS method is one of the effective conjugate gradient methods in solving the unconstrained optimization problems. The paper presents a modified LS method on the basis of the famous LS method and proves the strong global convergence for the uniformly convex functions and the global convergence for general functions under the strong Wolfe line search. The numerical experiments show that the modified LS method is very effective in practice.

A replaceable liposomal aptamer for the ultrasensitive and rapid detection of biotin

Science.gov (United States)

Sung, Tzu-Cheng; Chen, Wen-Yih; Shah, Pramod; Chen, Chien-Sheng

2016-02-01

Biotin is an essential vitamin which plays an important role for maintaining normal physiological function. A rapid, sensitive, and simple method is necessary to monitor the biotin level. Here, we reported a replacement assay for the detection of biotin using a replaceable liposomal aptamer. Replacement assay is a competitive assay where a sample analyte replaces the labeled competitor of analyte out of its biorecognition element on a surface. It is user friendly and time-saving because of washing free. We used aptamer as a competitor, not a biorecognition element as tradition. To label aptamers, we used cholesterol-conjugated aptamers to tag signal-amplifying-liposomes. Without the need of conjugation procedure, aptamers can be easily incorporated into the surface of dye-encapsulating liposomes. Two aptamers as competitors of biotin, ST-21 and ST-21M with different affinities to streptavidin, were studied in parallel for the detection of biotin using replacement assays. ST-21 and ST-21M aptamers reached to limits of detection of 1.32 pg/80 μl and 0.47 pg/80 μl, respectively. The dynamic ranges of our assays using ST-21 and ST-21M aptamers were seven and four orders of magnitude, respectively. This assay can be completed in 20 minutes without washing steps. These results were overall better than previous reported assays.

Evaluation of B3LYP, X3LYP, and M06-Class Density Functionals for Predicting the Binding Energies of Neutral, Protonated, and Deprotonated Water Clusters.

Science.gov (United States)

Bryantsev, Vyacheslav S; Diallo, Mamadou S; van Duin, Adri C T; Goddard, William A

2009-04-14

In this paper we assess the accuracy of the B3LYP, X3LYP, and newly developed M06-L, M06-2X, and M06 functionals to predict the binding energies of neutral and charged water clusters including (H2O)n, n = 2-8, 20), H3O(+)(H2O)n, n = 1-6, and OH(-)(H2O)n, n = 1-6. We also compare the predicted energies of two ion hydration and neutralization reactions on the basis of the calculated binding energies. In all cases, we use as benchmarks calculated binding energies of water clusters extrapolated to the complete basis set limit of the second-order Møller-Plesset perturbation theory with the effects of higher order correlation estimated at the coupled-cluster theory with single, double, and perturbative triple excitations in the aug-cc-pVDZ basis set. We rank the accuracy of the functionals on the basis of the mean unsigned error (MUE) between calculated benchmark and density functional theory energies. The corresponding MUE (kcal/mol) for each functional is listed in parentheses. We find that M06-L (0.73) and M06 (0.84) give the most accurate binding energies using very extended basis sets such as aug-cc-pV5Z. For more affordable basis sets, the best methods for predicting the binding energies of water clusters are M06-L/aug-cc-pVTZ (1.24), B3LYP/6-311++G(2d,2p) (1.29), and M06/aug-cc-PVTZ (1.33). M06-L/aug-cc-pVTZ also gives more accurate energies for the neutralization reactions (1.38), whereas B3LYP/6-311++G(2d,2p) gives more accurate energies for the ion hydration reactions (1.69).

Reversing multidrug resistance in Caco-2 by silencing MDR1, MRP1, MRP2, and BCL-2/BCL-xL using liposomal antisense oligonucleotides.

Directory of Open Access Journals (Sweden)

Yu-Li Lo

Full Text Available Multidrug resistance (MDR is a major impediment to chemotherapy. In the present study, we designed antisense oligonucleotides (ASOs against MDR1, MDR-associated protein (MRP1, MRP2, and/or BCL-2/BCL-xL to reverse MDR transporters and induce apoptosis, respectively. The cationic liposomes (100 nm composed of N-[1-(2,3-dioleyloxypropyl]-n,n,n-trimethylammonium chloride and dioleoyl phosphotidylethanolamine core surrounded by a polyethylene glycol (PEG shell were prepared to carry ASOs and/or epirubicin, an antineoplastic agent. We aimed to simultaneously suppress efflux pumps, provoke apoptosis, and enhance the chemosensitivity of human colon adenocarcinoma Caco-2 cells to epirubicin. We evaluated encapsulation efficiency, particle size, cytotoxicity, intracellular accumulation, mRNA levels, cell cycle distribution, and caspase activity of these formulations. We found that PEGylated liposomal ASOs significantly reduced Caco-2 cell viability and thus intensified epirubicin-mediated apoptosis. These formulations also decreased the MDR1 promoter activity levels and enhanced the intracellular retention of epirubicin in Caco-2 cells. Epirubicin and ASOs in PEGylated liposomes remarkably decreased mRNA expression levels of human MDR1, MRP1, MRP2, and BCL-2. The combined treatments all significantly increased the mRNA expressions of p53 and BAX, and activity levels of caspase-3, -8, and -9. The formulation of epirubicin and ASOs targeting both pump resistance of MDR1, MRP1, and MRP2 and nonpump resistance of BCL-2/BCL-xL demonstrated more superior effect to all the other formulations used in this study. Our results provide a novel insight into the mechanisms by which PEGylated liposomal ASOs against both resistance types act as activators to epirubicin-induced apoptosis through suppressing MDR1, MRP1, and MRP2, as well as triggering intrinsic mitochondrial and extrinsic death receptor pathways. The complicated regulation of MDR highlights the necessity

Effects of 5-nitro-2-furaldehyde on the radiation damage of liposomes

International Nuclear Information System (INIS)

Kuropteva, Z.V.; Sprinz, H.; Schaefer, H.; Winkler, E.

1986-01-01

By means of 1 H-NMR spectroscopy the influence of 5-nitro-2-furaldehyde (NF) on the permeation of Eu 3+ ions into irradiated liposomes of egg yolk lecithin was examined. In the presence of NF there was an increase in the permeability of irradiated liposomes. The damage of the liposomes was quantified spectrophotometrically in terms of diene conjugation. (author)

Identification of a variant form of tyrosine phosphatase LYP

Directory of Open Access Journals (Sweden)

Ho Wanting T

2010-11-01

Full Text Available Abstract Background Protein tyrosine phosphatases (PTPs are important cell signaling regulators with major pathological implications. LYP (also known as PTPN22 is an intracellular enzyme initially found to be predominately expressed in lymphocytes. Importantly, an allelic R620W variant of LYP is strongly associated with multiple autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and autoimmune thyroid disease. Results In this study, we isolated a novel isoform of LYP designated LYP3. LYP3 differs from LYP1, the known isoform of LYP, in that it lacks a 28 amino acid segment right after the R620W site embedded in a proline-rich protein-protein interaction motif. Genomic sequence analysis revealed that LYP3 resulted from alternative splicing of the LYP gene located on chromosome 1p 13.3-13.1. Reverse transcription PCR analyses of 48 human tissues demonstrated that both LYP1 and LYP3 are predominantly expressed in primary and secondary lymphoid tissues but the relative expression levels of the two isoforms varies in different human tissues and individuals. Conclusions We thus identified a new variant form of LYP and conducted a comprehensive analysis of LYP tissue expressions. Considering the pathogenesis of LYP R620W, we believe that the expression of LYP3 may have an important role in regulating activity and function of LYP and may be implicated in autoimmune diseases.

A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

Science.gov (United States)

Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

2006-01-01

Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

Tumor targeting using liposomal antineoplastic drugs

Directory of Open Access Journals (Sweden)

Jörg Huwyler

2008-03-01

Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

Support vector machine regression (LS-SVM)--an alternative to artificial neural networks (ANNs) for the analysis of quantum chemistry data?

Science.gov (United States)

Balabin, Roman M; Lomakina, Ekaterina I

2011-06-28

A multilayer feed-forward artificial neural network (MLP-ANN) with a single, hidden layer that contains a finite number of neurons can be regarded as a universal non-linear approximator. Today, the ANN method and linear regression (MLR) model are widely used for quantum chemistry (QC) data analysis (e.g., thermochemistry) to improve their accuracy (e.g., Gaussian G2-G4, B3LYP/B3-LYP, X1, or W1 theoretical methods). In this study, an alternative approach based on support vector machines (SVMs) is used, the least squares support vector machine (LS-SVM) regression. It has been applied to ab initio (first principle) and density functional theory (DFT) quantum chemistry data. So, QC + SVM methodology is an alternative to QC + ANN one. The task of the study was to estimate the Møller-Plesset (MPn) or DFT (B3LYP, BLYP, BMK) energies calculated with large basis sets (e.g., 6-311G(3df,3pd)) using smaller ones (6-311G, 6-311G*, 6-311G**) plus molecular descriptors. A molecular set (BRM-208) containing a total of 208 organic molecules was constructed and used for the LS-SVM training, cross-validation, and testing. MP2, MP3, MP4(DQ), MP4(SDQ), and MP4/MP4(SDTQ) ab initio methods were tested. Hartree-Fock (HF/SCF) results were also reported for comparison. Furthermore, constitutional (CD: total number of atoms and mole fractions of different atoms) and quantum-chemical (QD: HOMO-LUMO gap, dipole moment, average polarizability, and quadrupole moment) molecular descriptors were used for the building of the LS-SVM calibration model. Prediction accuracies (MADs) of 1.62 ± 0.51 and 0.85 ± 0.24 kcal mol(-1) (1 kcal mol(-1) = 4.184 kJ mol(-1)) were reached for SVM-based approximations of ab initio and DFT energies, respectively. The LS-SVM model was more accurate than the MLR model. A comparison with the artificial neural network approach shows that the accuracy of the LS-SVM method is similar to the accuracy of ANN. The extrapolation and interpolation results show that LS-SVM is

Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging

DEFF Research Database (Denmark)

Jensen, Andreas I.; Severin, Gregory W.; Hansen, Anders Elias

2018-01-01

to 8days. Liposomes with surface-conjugated 52Mn-DOTA exhibited a significantly shorter plasma half-life (T½=14.4h) when compared to the remote-loaded counterpart (T½=21.3h), whereas surface-conjugated 64Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.......9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52Mn, and furthermore that 52Mn-DOTA may be unstable in vivo whereas 64Cu-DOTA appears suitable for quantitative imaging....... protocols for radiolabeling liposomes with 52Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 (64Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal...

Application of Ulex europaeus agglutinin I-modified liposomes for oral vaccine: Ex Vivo bioadhesion and in Vivo immunity.

Science.gov (United States)

Li, KeXin; Zhao, Xiuli; Xu, Shiyi; Pang, DaHai; Yang, ChunRong; Chen, DaWei

2011-01-01

The conjugation of Ulex europaeus agglutinin I (UEAI) onto surface of liposomes has been demonstrated to effectively improve the intestinal absorption of antigen, subsequently induced strong mucosal and systemic immune responses. In this context, we prepared bovine serum albumin (BSA)-encapsulating UEAI-modified liposomes (UEAI-LIP) and unmodified ones (LIP). The specific bioadhesion on mice gastro-intestinal mucosa was studied ex vivo. An important increase of interaction between UEAI-conjugated liposomes and the intestinal segments with Peyer's Patches (PPs) was observed compared with the unconjugated one (p<0.01). However, under the presence of α-L-fucose, which is the reported specific sugar for UEAI, specifically inhibited the activity of these conjugates. The immune-stimulating activity in vivo was studied by measuring immunoglobulin G (IgG) levels in serum and immunoglobulin A (IgA) levels in intestinal mucosal secretions following oral administration of BSA solution, LIP and UEAI-LIP in mice. Results indicate that antigen encapsulated in liposomes, especially the UEAI-modified ones, was favorable for inducing immune response. At 42 d after the first immunization, the highest IgG and IgA antibody levels produced by UEAI-LIP occurred, respectively showing 4.4-fold and 5-fold higher levels compared to those of the groups receiving BSA alone. This data demonstrated high potential of UEAI-modified liposomes for their use as carrier for oral vaccines.

Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer.

Science.gov (United States)

Bansal, Divya; Gulbake, Arvind; Tiwari, Jyoti; Jain, Sanjay K

2016-01-01

Folic Acid conjugated liposomes encapsulating Oxaliplatin (L-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing L-OHP was administered orally at the dose of 10mg L-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after oral administration. In vivo data showed that folic acid coupled liposomes entrapped in alginate beads delivered 2.82 ± 0.58 and 21.52 ± 2.76 μg L-OHP/g tissues in the colon and tumor after 12h, reflecting its targeting potential to colon and tumor. The results clearly demonstrate that Eudragit coated calcium alginate beads bearing folic acid coupled liposome can be used as a prospective carrier for drug delivery to colon specific tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

Poly(amino acid)s: next-generation coatings for long-circulating liposomes

NARCIS (Netherlands)

Romberg, B.

2007-01-01

Incorporation of a lipid conjugate of a water-soluble polymer into liposomes can reduce the adhesion of plasma proteins that would otherwise cause rapid recognition and removal of the liposomes by phagocytes. Such polymer-coated liposomes show prolonged circulation property and passive targeting to

Summary: after LS1

International Nuclear Information System (INIS)

Pojer, M.; Schmidt, R.

2012-01-01

After LS1 the energy will be about 6.5 TeV. The physics potential of LHC is determined by the integrated luminosity useful for the experiments and not only by the peak luminosity. The integrated luminosity is determined by the peak luminosity, the luminosity decay and the efficiency of operation (availability). In this session two of these parameters are addressed, the peak luminosity and the availability. In this paper peak luminosity is discussed through the performance potential of the injectors and through the global performance reach of LHC after LS1. LHC availability is tackled through the issues of the reliability of the magnet powering and of the beam system and of the occurrence of quenches

Oxidative stability of Liposomes composed of docosahexaenoic acid-containing phospholipids

DEFF Research Database (Denmark)

Vikbjerg, Anders Falk; Andresen, Thomas Lars; Jørgensen, Kent

2007-01-01

Oxidative stability of liposomes made of (Docosahexaenoic acid) DHA-containing phosphatidylcholine (PC) was examined during preparation and storage. After preparation of the liposomes, the concentration of primary (conjugated dienes) and secondary oxidation products (Thiobarbituric acid...

LS1: exciting times ahead

CERN Multimedia

Caroline Duc

2013-01-01

As the first and last proton-lead run of 2013 draws to a close, the extensive upgrade and maintenance programme of the LHC's first long shutdown (LS1) is about to get under way.   The LHC has provided physicists with a huge quantity of data to analyse since the first physics run in 2009. Now it's time for the machine, along with CERN's other accelerators, to get a facelift. LS1 will start on 13 February 2013, but this doesn’t mean that life at the Laboratory will be any less rich and exciting. Although there will be no collisions for a period of almost two years, the whole CERN site will be a hive of activity, with large-scale work under way to modernise the infrastructure and prepare the LHC for operation at higher energy. "A whole series of renovation work will be carried out around the LHC during LS1,” explains Simon Baird, deputy head of the EN Department. "The key driver is of course the consolidation of the 10,170 high-curren...

Body distributioin of RGD-mediated liposome in brain-targeting drug delivery.

Science.gov (United States)

Qin, Jing; Chen, DaWei; Hu, Haiyang; Qiao, MingXi; Zhao, XiuLi; Chen, Baoyu

2007-09-01

RGD conjugation liposomes (RGD-liposomes) were evaluated for brain-targeting drug delivery. The flow cytometric in vitro study demonstrated that RGD-liposomes could bind to monocytes and neutrophils effectively. Ferulic acid (4-hydroxy-3-methoxycinnamic, FA) was loaded into liposomes. Rats were subjected to intrastriatal microinjections of 100 units of human recombinant IL-1beta to produce brain inflammation and caudal vein injection of three formulations (FA solution, FA liposome and RGD-coated FA liposome). Animals were sacrificed 15, 30, 60 and 120 min after administration to study the body distribution of the FA in the three formulations. HPLC was used to determine the concentration of FA in vivo with salicylic acid as internal standard. The results of body distribution indicated that RGD-coated liposomes could be mediated into the brain with a 6-fold FA concentration compared to FA solution and 3-fold in comparison to uncoated liposome. Brain targeted delivery was achieved and a reduction in dosage might be allowed.

Evaluation of B3LYP, X3LYP, and M06-class density functionals for predicting the binding energies of neutral, protonated, and deprotonated water clusters

OpenAIRE

Bryantsev, Vyacheslav S.; Diallo, Mamadou S.; van Duin, Adri C. T.; Goddard, William A., III

2009-01-01

In this paper we assess the accuracy of the B3LYP, X3LYP, and newly developed M06-L, M06-2X, and M06 functionals to predict the binding energies of neutral and charged water clusters including (H_2O)_n, n = 2−8, 20), H_3O+(H_2O_)n, n = 1−6, and OH−(H_2O)_n, n = 1−6. We also compare the predicted energies of two ion hydration and neutralization reactions on the basis of the calculated binding energies. In all cases, we use as benchmarks calculated binding energies of water clusters extrapolate...

MRI contrast agent for targeting glioma: interleukin-13 labeled liposome encapsulating gadolinium-DTPA.

Science.gov (United States)

Liu, Xiaoli; Madhankumar, Achuthamangalam B; Miller, Patti A; Duck, Kari A; Hafenstein, Susan; Rizk, Elias; Slagle-Webb, Becky; Sheehan, Jonas M; Connor, James R; Yang, Qing X

2016-05-01

Detection of glioma with MRI contrast agent is limited to cases in which the blood-brain barrier (BBB) is compromised as contrast agents cannot cross the BBB. Thus, an early-stage infiltrating tumor is not detectable. Interleukin-13 receptor alpha 2 (IL-13Rα2), which has been shown to be overexpressed in glioma, can be used as a target moiety. We hypothesized that liposomes conjugated with IL-13 and encapsulating MRI contrast agent are capable of passing through an intact BBB and producing MRI contrast with greater sensitivity. The targeted MRI contrast agent was created by encapsulating Magnevist (Gd-DTPA) into liposomes conjugated with IL-13 and characterized by particle size distribution, cytotoxicity, and MRI relaxivity. MR image intensity was evaluated in the brain in normal mice post injection of Gd-DTPA and IL-13-liposome-Gd-DTPA one day apart. The specificity for glioma detection by IL-13-liposome-Gd-DTPA was demonstrated in an intracranial glioma mouse model and validated histologically. The average size of IL-13-liposome-Gd-DTPA was 137 ± 43 nm with relaxivity of 4.0 ± 0.4 L/mmole-s at 7 Tesla. No significant cytotoxicity was observed with MTS assay and serum chemistry in mice. The MRI signal intensity was enhanced up to 15% post injection of IL-13-liposome-Gd-DTPA in normal brain tissue following a similar time course as that for the pituitary gland outside of the BBB. MRI enhanced by IL-13-liposome-Gd-DTPA detected small tumor masses in addition to those seen with Magnevist-enhanced MRI. IL-13-liposome-Gd-DTPA is able to pass through the uncompromised BBB and detect an early stage glioma that cannot be seen with conventional contrast-enhanced MRI. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Covalent modification of serum transferrin with phospholipid and incorporation into liposomal membranes

DEFF Research Database (Denmark)

Afzelius, P; Demant, E J; Hansen, Gert Helge

1989-01-01

A method is described for incorporation of water-soluble proteins into liposomal membranes using covalent protein-phospholipid conjugates in detergent solution. A disulfide derivative of phosphatidylethanolamine containing a reactive N-hydroxysuccinimide ester group is synthesized, and the deriva......A method is described for incorporation of water-soluble proteins into liposomal membranes using covalent protein-phospholipid conjugates in detergent solution. A disulfide derivative of phosphatidylethanolamine containing a reactive N-hydroxysuccinimide ester group is synthesized...

A mid-term report for LS1

CERN Multimedia

2014-01-01

As the LHC’s first long shutdown, LS1, enters its second calendar year, it’s a good time for a mid-term report on how things are progressing.    Towards the end of last year, I had the pleasure to go down to the LHC tunnel to witness the closure of the first of the machine’s sectors to be completed. As I write, three sectors are now closed up, with a fourth not far behind. These are important milestones, and you can follow progress in detail in the regular LS1 reports in the Bulletin. They show that we’re on schedule for physics to resume in about a year from now, but more than that, they are an important reminder of the LS1 motto: safety, quality, schedule. It is fantastic news that we are on schedule, and testimony to the rigour that went into the detailed and complex planning of all the work that had to be undertaken in LS1. But more important than the schedule is the fact that we’ve carried out the work safely and that the qualit...

Remediation of Learning Disable Children Following L.S. Vygotsky's Approach

Directory of Open Access Journals (Sweden)

Janna M. Glozman

2011-01-01

Full Text Available The paper defines remediating education, its peculiarities against trasitional education, main tasks and principles, based upon the cultural-historical theory of L.S. Vygotsky. Base functional systems formed during remediation are discussed. Peculiarities of individual, group and dyadic methods of remediation are described with regard to its potential for mediating child's activity.

Prediction of fetal lung maturity using the lecithin/sphingomyelin (L/S) ratio analysis with a simplified sample preparation, using a commercial microtip-column combined with mass spectrometric analysis.

Science.gov (United States)

Kwak, Ho-Seok; Chung, Hee-Jung; Choi, Young Sik; Min, Won-Ki; Jung, So Young

2015-07-01

Fetal lung maturity is estimated using the lecithin/sphingomyelin ratio (L/S ratio) in amniotic fluid and it is commonly measured with thin-layer chromatography (TLC). The TLC method is time consuming and technically difficult; however, it is widely used because there is no alternative. We evaluated a novel method for measuring the L/S ratio, which involves a tip-column with a cation-exchange resin and mass spectrometry. Phospholipids in the amniotic fluid were extracted using methanol and chloroform. Choline-containing phospholipids such as lecithin and sphingomyelin were purified by passing them through the tip-column. LC-MS/MS and MALDI-TOF were used to directly analyze the purified samples. The L/S ratio by mass spectrometry was calculated from the sum peak intensity of the six lecithin, and that of sphingomyelin 34:1. In 20 samples, the L/S ratio determined with TLC was significantly correlated with that obtained by LC-MS/MS and MALDI-TOF. There was a 100% concordance between the L/S ratio by TLC and that by LC-MS/MS (kappa value=1.0). The concordance between the L/S ratio by TLC and that by MALDI-TOF was also 100% (kappa value=1.0). Our method provides a faster, simpler, and more reliable assessment of fetal lung maturity. The L/S ratio measured by LC-MS/MS and MALDI-TOF offers a compelling alternative method to traditional TLC. Copyright © 2015 Elsevier B.V. All rights reserved.

Wheat germ agglutinin-conjugated liposomes incorporated with cardiolipin to improve neuronal survival in Alzheimer’s disease treatment

Directory of Open Access Journals (Sweden)

Kuo YC

2017-03-01

Full Text Available Yung-Chih Kuo,1 Che-Yu Lin,1 Jay-Shake Li,2 Yung-I Lou3 1Department of Chemical Engineering, 2Department of Psychology, National Chung Cheng University, Chia-Yi, 3Department of Accounting, Providence University, Taichung, Taiwan, Republic of China Abstract: Curcumin (CRM and nerve growth factor (NGF were entrapped in liposomes (LIP with surface wheat germ agglutinin (WGA to downregulate the phosphorylation of kinases in Alzheimer’s disease (AD therapy. Cardiolipin (CL-conjugated LIP carrying CRM (CRM-CL/LIP and also carrying NGF (NGF-CL/LIP were used with AD models of SK-N-MC cells and Wistar rats after an insult with β-amyloid peptide (Aβ. We found that CRM-CL/LIP inhibited the expression of phosphorylated p38 (p-p38, phosphorylated c-Jun N-terminal kinase (p-JNK, and p-tau protein at serine 202 and prevented neurodegeneration of SK-N-MC cells. In addition, NGF-CL/LIP could enhance the quantities of p-neurotrophic tyrosine kinase receptor type 1 and p-extracellular signal-regulated kinase 5 for neuronal rescue. Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood–brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats. Based on the marker expressions and in vivo evidence, current LIP carriers can be promising drug delivery systems to protect nervous tissue against Aβ-induced apoptosis in the brain during the clinical management of AD. Keywords: liposome, Alzheimer’s disease, β-amyloid, neurodegeneration, blood–brain barrier, wheat germ agglutinin

[Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice].

Science.gov (United States)

Zhang, Na; Ping, Qi-neng; Xu, Wen-fang

2004-12-01

To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination. The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration. The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.

P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.

Science.gov (United States)

Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza

2014-12-01

Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Safety, Quality, Schedule: the motto of LS1

CERN Multimedia

2013-01-01

The LHC’s first long shutdown, LS1, is a marathon that began on 16 February and will take us through to the beginning of 2015. Just as Olympic marathon runners have a motto, Citius, Altius, Fortius, so the athletes of LS1 work to the mantra of Safety, Quality, Schedule. Four months into LS1, they have settled into their rhythm, and things are going to plan.   The first task of LS1 was to bring the LHC up to room temperature - this was achieved in just 10 weeks. In parallel, preliminary tests for electrical quality assurance and leaks revealed essentially the level of wear and tear we’d expect after three years of running. One slightly anxious moment came when we looked at the RF fingers – the devices that ensure electrical contact in the beam pipes as they pass from one magnet to the next. Those of you with long memories will recall that before start-up, some of these got damaged at warm-up. The good news today is that with all eight sectors test...

Bacillus amyloliquefaciens L-S60 Reforms the Rhizosphere Bacterial Community and Improves Growth Conditions in Cucumber Plug Seedling

Directory of Open Access Journals (Sweden)

Yuxuan Qin

2017-12-01

Full Text Available Vegetable plug seedling has become the most important way to produce vegetable seedlings in China. This seedling method can significantly improve the quality and yield of vegetables compared to conventional methods. In the process of plug seedling, chemical fertilizers or pesticides are often used to improve the yield of the seedlings albeit with increasing concerns. Meanwhile, little is known about the impact of beneficial bacteria on the rhizosphere microbiota and the growth conditions of vegetables during plug seedling. In this study, we applied a culture-independent next-generation sequencing-based approach and investigated the impact of a plant beneficial bacterium, Bacillus amyloliquefaciens L-S60, on the composition and dynamics of rhizosphere microbiota and the growth conditions of cucumbers during plug seedling. Our results showed that application of L-S60 significantly altered the structure of the bacterial community associated with the cucumber seedling; presence of beneficial rhizosphere species such as Bacillus, Rhodanobacter, Paenibacillus, Pseudomonas, Nonomuraea, and Agrobacterium was higher upon L-S60 treatment than in the control group. We also measured the impact of L-S60 application on the physiological properties of the cucumber seedlings as well as the availability of main mineral elements in the seedling at different time points during the plug seedling. Results from those measurements indicated that L-S60 application promoted growth conditions of cucumber seedlings and that more available mineral elements were detected in the cucumber seedlings from the L-S60 treated group than from the control group. The findings in this study provided evidence for the beneficial effects of plant growth-promoting rhizosphere bacteria on the bacterial community composition and growth conditions of the vegetables during plug seedling.

Accurate pKa Calculation of the Conjugate Acids of Alkanolamines, Alkaloids and Nucleotide Bases by Quantum Chemical Methods

NARCIS (Netherlands)

Gangarapu, S.; Marcelis, A.T.M.; Zuilhof, H.

2013-01-01

The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum

SPS completes LS1 activities

CERN Multimedia

Katarina Anthony

2014-01-01

On 27 June, the SPS closed its doors to the LS1 engineers, bringing to an end almost 17 months of activities. The machine now enters the hardware-testing phase in preparation for an October restart.   Photo 1: The SPS transfer tunnel, TT10, reinforced with steal beams. Having completed their LS1 activities right on schedule (to the day!), the SPS team is now preparing the machine for its restart. Over the next eight weeks, hardware tests of the SPS dipole and quadrupole power converters will be underway, led by the TE-EPC (Electrical Power Converters) team. "OP start-up test activities will also be running in parallel, utilising the off hours when EPC is not using the machine," says David McFarlane, the SPS technical coordinator from the Engineering Department. "The primary beam testing phase will start at the beginning of September, once hardware tests and DSO safety tests have been completed." It has been a long journey to this point, with several major...

LS1: electrical engineering upgrades and consolidation

International Nuclear Information System (INIS)

Duval, F.

2012-01-01

3 different types of activities are planned by the Engineering Department Electrical Engineering (EN-EL) Group for the first long shut down (LS1). First, the consolidation of EN-EL's ageing infrastructure elements. It is part of a 15- year programme aiming at increasing the reliability and availability of the power distribution network. Secondly, the maintenance of the accelerators infrastructure. In addition to the usual periodic operations and those delayed until LS1, the group will address more demanding activities like the replacement campaigns for irradiated cables and non-radiation resistant fibres as well as the removal of unused cables in particularly overcrowded areas. Thirdly, a vast amount of user copper and optical fibre cabling requests: EN-EL estimates that only 50% of LS1 requests are currently known. The main activities will be EN-EL's contributions to the R2E project, BE-BI upgrade projects, and the RF upgrade project in SPS BA3

Liposomes as potential carrier system for targeted delivery of polyene antibiotics.

Science.gov (United States)

Naik, Suresh R; Desai, Sandhya K; Shah, Priyank D; Wala, Santosh M

2013-09-01

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

Fluorescence Resonance Energy Transfer in Polydiacetylene Liposomes

Science.gov (United States)

Li, Xuelian; Matthews, Shelton; Kohli, Punit

2009-01-01

Conjugated polydiacetylene (PDA) possessing stimuli-responsive properties has been intensively investigated for developing efficient sensors. We report here fluorescence resonance energy transfer (FRET) in liposomes synthesized using different molar ratios of dansyl-tagged diacetylene and diacetylene–carboxylic acid monomers. Photopolymerization of diacetylene resulted in cross-linked PDA liposomes. We used steady-state electronic absorption, emission, and fluorescence anisotropy (FA) analysis to characterize the thermal-induced FRET between dansyl fluorophores (donor) and PDA (acceptor). We found that the monomer ratio of acceptor to donor (Rad) and length of linkers (functional part that connects dansyl fluorophores to the diacetylene group in the monomer) strongly affected FRET. For Rad = 10 000, the acceptor emission intensity was amplified by more than 18 times when the liposome solution was heated from 298 to 338 K. A decrease in Rad resulted in diminished acceptor emission amplification. This was primarily attributed to lower FRET efficiency between donors and acceptors and a higher background signal. We also found that the FRET amplification of PDA emissions after heating the solution was much higher when dansyl was linked to diacetylene through longer and flexible linkers than through shorter linkers. We attributed this to insertion of dansyl in the bilayer of the liposomes, which led to an increased dansyl quantum yield and a higher interaction of multiple acceptors with limited available donors. This was not the case for shorter and more rigid linkers where PDA amplification was much smaller. The present studies aim at enhancing our understanding of FRET between fluorophores and PDA-based conjugated liposomes. Furthermore, receptor tagged onto PDA liposomes can interact with ligands present on proteins, enzymes, and cells, which will produce emission sensing signal. Therefore, using the present approach, there exist opportunities for designing FRET

Remote-loading of liposomes with manganese-52 and in vivo evaluation of the stabilities of 52Mn-DOTA and 64Cu-DOTA using radiolabelled liposomes and PET imaging.

Science.gov (United States)

Jensen, Andreas I; Severin, Gregory W; Hansen, Anders E; Fliedner, Frederikke P; Eliasen, Rasmus; Parhamifar, Ladan; Kjær, Andreas; Andresen, Thomas L; Henriksen, Jonas R

2018-01-10

Liposomes are nanoparticles used in drug delivery that distribute over several days in humans and larger animals. Radiolabeling with long-lived positron emission tomography (PET) radionuclides, such as manganese-52 ( 52 Mn, T½=5.6days), allow the imaging of this biodistribution. We report optimized protocols for radiolabeling liposomes with 52 Mn, through both remote-loading and surface labeling. For comparison, liposomes were also remote-loaded and surface labeled with copper-64 ( 64 Cu, T½=12.7h) through conventional means. The chelator DOTA was used in all cases. The in vivo stability of radiometal chelates is widely debated but studies that mimic a realistic in vivo setting are lacking. Therefore, we employed these four radiolabeled liposome types as platforms to demonstrate a new concept for such in vivo evaluation, here of the chelates 52 Mn-DOTA and 64 Cu-DOTA. This was done by comparing "shielded" remote-loaded with "exposed" surface labeled variants in a CT26 tumor-bearing mouse model. Remote loading (90min at 55°C) and surface labeling (55°C for 2h) of 52 Mn gave excellent radiolabeling efficiencies of 97-100% and 98-100% respectively, and the liposome biodistribution was imaged by PET for up to 8days. Liposomes with surface-conjugated 52 Mn-DOTA exhibited a significantly shorter plasma half-life (T ½ =14.4h) when compared to the remote-loaded counterpart (T ½ =21.3h), whereas surface-conjugated 64 Cu-DOTA cleared only slightly faster and non-significantly, when compared to remote-loaded (17.2±2.9h versus 20.3±1.2h). From our data, we conclude the successful remote-loading of liposomes with 52 Mn, and furthermore that 52 Mn-DOTA may be unstable in vivo whereas 64 Cu-DOTA appears suitable for quantitative imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Modification of liposomes with proteins by dansyl-labeled heterobifunctional crosslinker.

Science.gov (United States)

Chen, Tao; Wang, Rutao; Lu, Tingting; Liang, Guozheng; Lu, Tingli

2011-07-01

The introduction of a fluorescent chromaphore into bifunctional crosslinkers results in a molecule with normal crosslinker properties and a fluorescent group for straightforward quantification. This work describes the synthesis of the dansyl-labeled heterobifunctional crosslinker N-succinimidyl ε-N-dansyl α-N-(acetylthio)acetyllysine (dansyl-ATA-lysine-NHS) containing reactive N-hydroxysuccinimidyl (NHS) ester and sulfhydryl groups. The application of this crosslinker to conjugation of bovine serum albumin (BSA) protein to the surface of a liposome containing maleimide functions is also demonstrated. BSA was modified with the dansyl-labeled crosslinker and subsequently conjugated to liposomes containing reactive phospholipid derivative N-[4-(p-maleimidophenyl)butyryl]phosphatidylethanolamine and the degree of modification and conjugation were quantitatively determined by measuring the fluorescence emission of the dansyl group. The reliability of the fluorescence quantification was confirmed by a micro bio-barcode assay protein assay.

Protein immobilization on the surface of liposomes via carbodiimide activation in the presence of N-hydroxysulfosuccinimide.

Science.gov (United States)

Bogdanov, A A; Klibanov, A L; Torchilin, V P

1988-04-25

A method of the covalent immobilization of proteins on the surface of liposomes, containing 10% (by mol) of N-glutaryl phosphatidylethanolamine, is described. Carboxylic groups of liposomal N-glutaryl phosphatidylethanolamine were activated in the presence of water-soluble carbodiimide and N-hydroxysulfosuccinimide and reacted subsequently with protein amino groups. The liposome-protein conjugates formed contained up to 5 x 10(-4) mol protein/mol lipid. Lectins (RCA1 and WGA) upon immobilization on liposomes retained saccharide specificity and the ability to agglutinate red blood cells. The immobilization of mouse monoclonal IgG in a ratio of 3.5 x 10(-4) mol IgG/mol lipid was achieved. The liposome activation in the absence of N-hydroxysulfosuccinimide resulted in a 2-fold decrease of protein coupling yields.

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

Science.gov (United States)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

2016-12-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

Science.gov (United States)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

2016-07-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

International Nuclear Information System (INIS)

De, A.K.; Ghosh, J.J.; Mandal, T.K.

1993-01-01

Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation

Ultraviolet radiation-induced lipid peroxidation in liposomal membrane: modification by capsaicin

Energy Technology Data Exchange (ETDEWEB)

De, A. K.; Ghosh, J. J.; Mandal, T. K. [University College of Science, Department of Biochemistry, 35 Ballygunge Circular Road, Calcutta 700-019 (India)

1993-07-01

Ultraviolet-radiation has been reported to cause lipid peroxidation in the liposomal membrane. In the present study, treatment with capsaicin, (8-methyl-n-vanillyl-6-nonenamide), the pungent principle of red hot pepper, was shown to modify UV-induced lipid peroxidation in the liposomal membrane. Treatment with low doses of capsaicin (less than 0.1 μg/mL of phosphatidyl choline liposome) produced a significant increase in UV-induced lipid peroxidation, while high doses (0.1-0.5 μg/mL of PC liposome) caused a significant decrease of UV-induced peroxidation.

Efficient L1 regularization-based reconstruction for fluorescent molecular tomography using restarted nonlinear conjugate gradient.

Science.gov (United States)

Shi, Junwei; Zhang, Bin; Liu, Fei; Luo, Jianwen; Bai, Jing

2013-09-15

For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1 regularization can protect the high-frequency information like edges while effectively reduce the image noise. However, the state-of-the-art L1 regularization-based algorithms for FMT reconstruction are expensive in memory, especially for large-scale problems. An efficient L1 regularization-based reconstruction algorithm based on nonlinear conjugate gradient with restarted strategy is proposed to increase the computational speed with low memory consumption. The reconstruction results from phantom experiments demonstrate that the proposed algorithm can obtain high spatial resolution and high signal-to-noise ratio, as well as high localization accuracy for fluorescence targets.

Design and syntheses of mono and multivalent mannosyl-lipoconjugates for targeted liposomal drug delivery.

Science.gov (United States)

Štimac, Adela; Cvitaš, Jelena TrmĿiĿ; Frkanec, Leo; Vugrek, Oliver; Frkanec, Ruža

2016-09-10

Multivalent mannosyl-lipoconjugates may be of interest for glycosylation of liposomes and targeted drug delivery because the mannose specifically binds to C-type lectin receptors on the particular cells. In this paper syntheses of two types of novel O-mannosides are presented. Conjugates 1 and 2 with a COOH- and NH2-functionalized spacer and the connection to a lysine and FmocNH-PEG-COOH, are described. The coupling reactions of prepared intermediates 6 and 4 with a PEGylated-DSPE or palmitic acid, respectively, are presented. Compounds 5, mono-, 8, di- and 12, tetravalent mannosyl-lipoconjugates, were synthesized. The synthesized compounds were incorporated into liposomes and liposomal preparations featuring exposed mannose units were characterized. Carbohydrate liposomal quartz crystal microbalance based assay has been established for studying carbohydrate-lectin binding. It was demonstrated that liposomes with incorporated mannosyl-lipoconjugates were effectively recognized by Con A and have great potential to be used for targeted liposomal drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Construction of a Liposome Dialyzer for preparation of high-value, small-volume liposome formulations

OpenAIRE

Adamala, Katarzyna; Engelhart, Aaron E.; Kamat, Neha P.; Jin, Lin; Szostak, Jack W.

2015-01-01

The liposome dialyzer is a small-volume equilibrium dialysis device, built from commercially available materials, that is designed for rapid exchange of small volumes of an extraliposomal reagent pool against a liposome preparation. The dialyzer is prepared by modification of commercially available dialysis cartridges and consists of a reactor with two 300 µL chambers and a 1.56 cm2 dialysis surface area. The dialyzer is prepared in three stages: 1) disassembly of dialysis cartridges to obtai...

LS1 general planning and strategy for the LHC, LHC injectors

International Nuclear Information System (INIS)

Foraz, K.

2012-01-01

The goal of Long Shutdown 1 (LS1) is to perform the full maintenance of equipment and the necessary consolidation and upgrade activities in order to ensure reliable LHC operation at nominal performance from mid-2014. LS1 is scheduled to last 20 months. LS1 not only concerns the LHC but also its injectors. To ensure resources will be available an analysis is in progress to detect conflict/overload and decide what is compulsory, what we can afford, and what can be postponed until LS2. The strategy, time key drivers, constraints, and draft schedule are presented here. (author)

Antibody derivatization and conjugation strategies: application in preparation of stealth immunoliposome to target chemotherapeutics to tumor.

Science.gov (United States)

Manjappa, Arehalli S; Chaudhari, Kiran R; Venkataraju, Makam P; Dantuluri, Prudhviraju; Nanda, Biswarup; Sidda, Chennakesavulu; Sawant, Krutika K; Murthy, Rayasa S Ramachandra

2011-02-28

A great deal of effort has been made over the years to develop liposomes that have targeting vectors (oligosaccharides, peptides, proteins and vitamins) attached to the bilayer surface. Most studies have focused on antibody conjugates since procedures for producing highly specific monoclonal antibodies are well established. Antibody conjugated liposomes have recently attracted a great deal of interest, principally because of their potential use as targeted drug delivery systems and in diagnostic applications. A number of methods have been reported for coupling antibodies to the surface of stealth liposomes. The objective of this review is to enumerate various strategies which are employed in the modification and conjugation of antibodies to the surface of stealth liposomes. This review also describes various derivatization techniques of lipids prior and after their use in the preparation of liposomes. The use of single chain variable fragments and affibodies as targeting ligands in the preparation of immunoliposomes is also discussed. Copyright © 2010 Elsevier B.V. All rights reserved.

Conjugal plasmid transfer (pAM beta 1) in Lactobacillus plantarum.

OpenAIRE

Shrago, A W; Chassy, B M; Dobrogosz, W J

1986-01-01

The streptococcal plasmid pAM beta 1 (erythromycin resistance) was transferred via conjugation from Streptococcus faecalis to Lactobacillus plantarum and was transferred among L. plantarum strains. Streptococcus sanguis Challis was transformed with pAM beta 1 isolated from these transconjugants, and transformants harboring intact pAM beta 1 could conjugate the plasmid back to L. plantarum.

IL WORKSHOP DI FONETICA IN ITALIANO L2/LS: ACCENTO DI PAROLA E DURATA SILLABICA

Directory of Open Access Journals (Sweden)

Lidia Calabrò

2016-09-01

Full Text Available Lavorare sugli aspetti fonetico-fonologici di una lingua straniera risulta quanto mai importante e fondamentale, soprattutto se la L1 degli apprendenti la L2/LS è molto distante. Attraverso un’esperienza iniziata con studenti sinofoni del progetto Marco Polo / Turandot, le attività inserite nel workshop di fonetica nell’italiano L2 si presentano come proposta di didattica integrativa al fine di sensibilizzare gli studenti ai tratti soprasegmentali della L2 a contrasto con quelli della loro L1. Nel presente contributo verranno presentate alcune attività riguardanti la percezione e la realizzazione della durata vocalica e della sillaba accentata attraverso attività collaborative e il movimento del corpo. Tutte le attività prevedono un coinvolgimento personale e totale del singolo apprendente e di tutta la classe in quanto il workshop si avvale di multimodalità, multimedialità e apprendimento collaborativo al fine di scoprire i suoni della L2 e riflettere sulla loro percezione e produzione. Italian L2/LS phonetic workshops: word accent and syllable duration Working on phonetics and the phonolgical aspects language is considered important and fundamental, above all if a learner’s L1 is distant from the SL. The activities described in the paper took place during a phonetic workshop in Italian as a second language with Chinese students enrolled in the Marco Polo/Turandot project. They can be considered a teaching technique aimed at raising student awareness about the SL supra-segmental aspects in contrast to their L1. Some activities related to vowel length and stress will be presented: perception and production, cooperative learning and body movement aimed at discovering and practicing vowel length in stressed syllables (phonic stress. The activities involved the students in a more personal, total and physical collaboration together with their classmates. The multimedia workshop was designed to be multimodal and cooperative, in order to

Electrodialytic extraction of heavy metals from Greenlandic MSWI fly ash as a function of remediation time and L/S ratio

DEFF Research Database (Denmark)

Kirkelund, Gunvor Marie; Jensen, Pernille Erland; Ottosen, Lisbeth M.

2013-01-01

, where the fly ash was suspended in distilled water in different liquid to solid (L/S) ratios. Remediation times of 7 and 14 days were tested and the current strength was 50 mA in all experiments. The highest removal was seen when an acidic pH in the fly ash suspension was obtained. In an experiment...... lasting 14 days with L/S 10, up to 60 % Cd, 45 % Zn, 20 % Ni and Ba was removed. Regardless of the remediation time and L/S ratio, the fraction of soluble Ba, Cr and Pb decreased due to the electrodialytic remediation. The electrodialytic remediation method showed potential as a treatment method...

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.)

Science.gov (United States)

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2018-01-01

Lettuce (Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce. PMID:29403510

Inflorescence Development and the Role of LsFT in Regulating Bolting in Lettuce (Lactuca sativa L.).

Science.gov (United States)

Chen, Zijing; Han, Yingyan; Ning, Kang; Ding, Yunyu; Zhao, Wensheng; Yan, Shuangshuang; Luo, Chen; Jiang, Xiaotang; Ge, Danfeng; Liu, Renyi; Wang, Qian; Zhang, Xiaolan

2017-01-01

Lettuce ( Lactuca sativa L.) is one of the most important leafy vegetable that is consumed during its vegetative growth. The transition from vegetative to reproductive growth is induced by high temperature, which has significant economic effect on lettuce production. However, the progression of floral transition and the molecular regulation of bolting are largely unknown. Here we morphologically characterized the inflorescence development and functionally analyzed the FLOWERING LOCUS T (LsFT) gene during bolting regulation in lettuce. We described the eight developmental stages during floral transition process. The expression of LsFT was negatively correlated with bolting in different lettuce varieties, and was promoted by heat treatment. Overexpression of LsFT could recover the late-flowering phenotype of ft-2 mutant. Knockdown of LsFT by RNA interference dramatically delayed bolting in lettuce, and failed to respond to high temperature. Therefore, this study dissects the process of inflorescence development and characterizes the role of LsFT in bolting regulation in lettuce.

Liposome based radiosensitizer cancer therapy

DEFF Research Database (Denmark)

Pourhassan, Houman

Liposome-encapsulated chemotherapeutics have been used in the treatment of a variety of cancers and are feasible for use as mono-therapeutics as well as for combination therapy in conjunction with other modalities. Despite widespread use of liposomal drugs in cancer patient care, insufficient drug...... biomolecules. By modulating the liposomal membrane, liposomes can become sensitive towards enzymatically-driven destabilization and/or functionalization, thereby allowing control of the release of encapsulated therapeutics within the diseased tissue upon intrinsic stimulation from tumor-associated enzymes...... in tumor-bearing mice.The safety and efficacy of sPLA2-sensitive liposomal L-OHP was assessed in sPLA2-deficient FaDu hypopharyngeal squamous cell carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. Also, the feasibility of multimodal cancer therapy employing L-OHP encapsulated in MMP...

Liposome as nanocarrier: Site targeted delivery in lung cancer

Directory of Open Access Journals (Sweden)

Najeeb Ullah

2017-08-01

Full Text Available Lung cancer is fatal and spreading rapidly worldwide. Different clinical strategies are applied to stop this cancer. As the lung is a delicate organ, special clinical applications must be used and nanodrugs delivery systems are the most important applications of all. This review discusses the lung problems such as lung cancer, lung inflammation and bronchi constrictions followed by repetitive intake of some drugs. The objective of this review is to study how nanodrug delivery systems were synthesized and used in lung disorder treatment especially in lung cancer. The authors studied some articles from 1989 to 2015. Liposome encapsulation was done in various ways for the delivery of different drugs such as metaproterenol into liposomes caused bronchodilation, immunoliposomes bearing antibodies for doxorubicin reduced 50% inhibitory effects, radioliposomes with high penetrating ability to peripheral airways, aerosol delivery systems with deep pulmonary deposition, polymeric drug delivery having potential to improve beneficial index of drug, solid lipid liposomes, liposomal gentamicin with altered different clinical susceptibilities of resistance, transferrin conjugated liposomes to deliver cytostatic drugs to site of lungs, anti-inflammatory drugs with mannosylated liposomes, liposomal suspensions with single stranded RNAs and peptide encapsulation of liposomes. This review indicates that many animals perished with intravenous administration of drugs but survived in liposomal targeting groups.

[Preparation of diclofenac sodium liposomes and its ocular pharmacokinetics].

Science.gov (United States)

Sun, Kao-xiang; Wang, Ai-ping; Huang, Li-jun; Liang, Rong-cai; Liu, Ke

2006-11-01

To prepare diclofenac sodium liposomes and observe its ocular pharmacokinetics in rabbits. The diclofenac sodium cationic liposomes were prepared by reverse-phase evaporation methods and the formula of liposome was optimized with uniform design. HPLC method was established and validated for the determination of diclofenac sodium in precornea, cornea and aqueous humor of rabbit eye. Liposome and eyedrop solution 50 microL with total 50 microg diclofenac sodium were instilled to eyes of rabbits, separately. Samples of tear, cornea and aqueous humor were collected at different time intervals after rabbits were sacrificed. The ocular pharmacokinetics was investigated by the concentration-time data of tear, cornea and aqueous humor. The mean particle size of the diclofenac sodium liposomes was 226.5 nm with zeta potential of + 18. 1 mV. The entrapment efficiency reached 63%. Compared with solution, liposome was characterized by slower clearance in precornea. The concentration of diclotenac in cornea and aqueous humor instilled with liposome were higher than that with eye-drop solution. Cmax of diclofenac sodium in aqueous humor instilled with liposome and eye-drop solution were (0.69 +/- 0.25) and (0.48 +/- 0.19) microg x mL(-1) and (36.68 +/- 11.7) and (21.82 +/- 8.6) microg x g(-1) in cornea, respectively. But no significant difference were found to Tmax in aqueous humor and cornea between liposome and eyedrop, T(1/2) of diclofenac in aqueous humor and cornea with liposoine were longer than that with eye-drop solution. The ocular bioavailability of liposome in aqueous humor was 211% compared with that of eyedrop. Diclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.

Characterization and enzyme-conjugation of a specific anti-L1 nanobody.

Science.gov (United States)

Minaeian, Sara; Rahbarizadeh, Fatemeh; Zarkesh Esfahani, Sayyed Hamid; Ahmadvand, Davoud

2012-01-01

Persistent infection of the human papillomaviruses (HPV) has been shown to result in cervical cancer and intraepithelial neoplasia. Early detection and screening programs are essential strategies against cervical cancer. A nanobody is the smallest antigen-binding fragment known and is derived from a camelid heavy-chain antibody. This tiny protein shows high solubility and stability. It can be produced cost-effectively with high yield production. In this study, we enriched a nanobody library against the L1 protein of HPV. Several colons were selected from this enriched library using monoclonal phage-enzyme linked immunosorbent assay (phage-ELISA) and analyzed for identification of nanobody genes. The expression of nanobody fragments was performed in Rosetta gami2. The C74 nanobody that showed strong binding to the L1 protein of HPV16 was selected, purified, and characterized by Western blotting and ELISA. The selected nanobody was tested for sensitivity, specificity, and affinity. A nanobody conjugated to horseradish peroxidase (HRP) was selected and used for detection of L1 protein of HPV16. This study demonstrates that the C74-HRP, due to its specificity and good binding affinity for a specific viral antigen, is a potential diagnostic tool that can be used as a promising reagent for the new generation of HPV diagnosis approaches.

A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

Directory of Open Access Journals (Sweden)

Li T

2013-10-01

Full Text Available Tianshu Li, Shinji TakeokaDepartment of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University (TWIns, Shinjuku-ku, Tokyo, JapanAbstract: Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol% of maleimide-polyethylene glycol (PEG to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG/cholesterol/poly(ethylene glycol 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG5000-DSPE/maleimide-PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG5000-DSPE/PEG5000-Glu2C18 at a molar ratio of 5:5:0.03:0.03. Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (≥2-fold internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of

Biophysical characterization of V3-lipopeptide liposomes influencing HIV-1 infectivity

International Nuclear Information System (INIS)

Rizos, Apostolos K.; Baritaki, Stavroula; Tsikalas, Ioannis; Doetschman, David C.; Spandidos, Demetrios A.; Krambovitis, Elias

2007-01-01

The V3-loop of the HIV-1 gp120 alters host cell immune function and modulates infectivity. We investigated biophysical parameters of liposome constructs with embedded lipopeptides from the principle neutralizing domain of the V3-loop and their influence on viral infectivity. Dynamic light scattering measurements showed liposome supramolecular structures with hydrodynamic radius of the order of 900 and 1300 nm for plain and V3-lipopeptide liposomes. Electron paramagnetic resonance measurements showed almost identical local microenvironment. The difference in liposome hydrodynamic radius was attributed to the fluctuating ionic environment of the V3-lipopeptide liposomes. In vitro HIV-1 infectivity assays showed that plain liposomes reduced virus production in all cell cultures, probably due to the hydrophobic nature of the aggregates. Liposomes carrying V3-lipopeptides with different cationic potentials restored and even enhanced infectivity (p < 0.05). These results highlight the need for elucidation of the involvement of lipid bilayers as dynamic components in supramolecular structures and in HIV-1 fusion mechanisms

Improving temporal resolution in fMRI using a 3D spiral acquisition and low rank plus sparse (L+S) reconstruction.

Science.gov (United States)

Petrov, Andrii Y; Herbst, Michael; Andrew Stenger, V

2017-08-15

Rapid whole-brain dynamic Magnetic Resonance Imaging (MRI) is of particular interest in Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). Faster acquisitions with higher temporal sampling of the BOLD time-course provide several advantages including increased sensitivity in detecting functional activation, the possibility of filtering out physiological noise for improving temporal SNR, and freezing out head motion. Generally, faster acquisitions require undersampling of the data which results in aliasing artifacts in the object domain. A recently developed low-rank (L) plus sparse (S) matrix decomposition model (L+S) is one of the methods that has been introduced to reconstruct images from undersampled dynamic MRI data. The L+S approach assumes that the dynamic MRI data, represented as a space-time matrix M, is a linear superposition of L and S components, where L represents highly spatially and temporally correlated elements, such as the image background, while S captures dynamic information that is sparse in an appropriate transform domain. This suggests that L+S might be suited for undersampled task or slow event-related fMRI acquisitions because the periodic nature of the BOLD signal is sparse in the temporal Fourier transform domain and slowly varying low-rank brain background signals, such as physiological noise and drift, will be predominantly low-rank. In this work, as a proof of concept, we exploit the L+S method for accelerating block-design fMRI using a 3D stack of spirals (SoS) acquisition where undersampling is performed in the k z -t domain. We examined the feasibility of the L+S method to accurately separate temporally correlated brain background information in the L component while capturing periodic BOLD signals in the S component. We present results acquired in control human volunteers at 3T for both retrospective and prospectively acquired fMRI data for a visual activation block-design task. We show that a SoS fMRI acquisition with an

Post LS1 schedule

CERN Document Server

Lamont, M

2014-01-01

The scheduling limits for a typical long year taking into account technical stops, machine development, spe- cial physics runs are presented. An attempt is then made to outline a ten year post LS1 schedule taking into account the disparate requirements outlined in the previous talks in this session. The demands on the planned long shutdowns and the impact of these demands on their proposed length will be discussed. The option of using ion running as a pre-shutdown cool-down period will be addressed.

Detection of antimycolic acid antibodies by liposomal biosensors

CSIR Research Space (South Africa)

Lemmer, Yolandy

2009-01-01

Full Text Available -mycolic acid antibodies by liposomal biosensors Running title: Antibody detection by liposomal biosensors Y. Lemmer1,3, S.T., Thanyani1, P.J. Vrey1, C.H.S. Driver2, L. Venter1, S. van Wyngaardt1, A.M.C. ten Bokum1, K.I. Ozoemena2, L.A. Pilcher2, D...H values. The anionic phosphatidyl residues (pKa ? 3.5) only become neutralised below pH 4, while the cationic state of choline (pKa = 13.9) is maintained over the full pH range measured (Tatulian et al., 1993). It is therefore expected that the stability...

Transcutaneous drug delivery by liposomes using fractional laser technology.

Science.gov (United States)

Fujimoto, Takahiro; Wang, Jian; Baba, Kazuki; Oki, Yuka; Hiruta, Yuki; Ito, Masayuki; Ito, Shinobu; Kanazawa, Hideko

2017-07-01

Transdermal delivery of hydrophilic peptides remains a challenge due to their poor cellular uptake and transdermal penetration. We hypothesize that combination of a CO 2 fractional laser to enhance percutaneous absorption and liposomes as transdermal carriers would improve skin penetration of hydrophilic drugs. NA. Liposomes were prepared using membrane fusion lipid dioleoylphosphatidylethanolamine, and used to deliver 5-carboxyfluorescein (CF) and fluorescein isothiocyanate-conjugated ovalbumin (OVA-FITC) as model hydrophilic peptide drugs. Liposome size was estimated by dynamic light scattering. Liposome uptake into murine macrophage cells and penetration or permeation into Yucatan micropig skin after irradiation by CO 2 fractional laser at varying energy levels (laser power and exposure duration) were investigated using Franz cell and fluorescence microscopy. Oxidative damage to the irradiated mouse skin was assessed by electron spin resonance. Size of CF and OVA-FITC encapsulated liposomes was 324 ± 75 nm. Cellular uptake of OVA-FITC delivered by liposomes was 10-fold higher (1,370 relative fluorescence units, RFU) than delivered in solution form (130 RFU). Fractional laser irradiation increased skin permeation rate of CF liposomes (0-10%) and OVA-FITC liposomes (4-40%) in a dose-dependent manner. Although peeling off the stratum corneum facilitated CF liposome penetration at low energy levels (2.69-3.29 J/cm 2 ; 10-20 W for 500 μs), drug permeation was similar (7-8%) in peeled or untreated skin at higher laser energy levels (6.06 J/cm 2 ; 20 W for 1,500 μs). FITC penetrated deeper in the skin after laser irradiation. However, OH, O2-, and VC reactive oxygen species were generated upon irradiation of the skin with a fractional CO 2 laser. Increasing laser power and irradiation, time increased liposome uptake by cells and penetration of peptide drugs across the skin in a dose-dependent manner. High-energy CO 2 fractional laser overcomes the

Summary of sessions 5 and 6: long shutdown 1 (LS1) 2013-2014

International Nuclear Information System (INIS)

Bordry, F.; Foraz, K.

2012-01-01

The minimal duration for LS1 is 20 months, meaning the time from physics to physics will be about 2 years. The actual start of LS1 is set for the 17. November 2012, which will allow the Liquid Helium emptying from the machine before Christmas. However, delivery dates for certain components are on the critical path of the experiments, which will allow the first beams for beam commissioning not before September 2014. Depending on the results of mid-2012 physics, the start date of LS1 will be reviewed. The actual plan for injectors is in line with the LHC plan, but the risk of running injectors for two years has to be assessed. The analysis of resources is progressing well throughout the complex (collaborations and internal mobility) and is being done according to priorities. Certain activities have already been postponed to LS2, and new requests will be carefully analyzed, as well as open issues

Enhanced spatial resolution in fluorescence molecular tomography using restarted L1-regularized nonlinear conjugate gradient algorithm.

Science.gov (United States)

Shi, Junwei; Liu, Fei; Zhang, Guanglei; Luo, Jianwen; Bai, Jing

2014-04-01

Owing to the high degree of scattering of light through tissues, the ill-posedness of fluorescence molecular tomography (FMT) inverse problem causes relatively low spatial resolution in the reconstruction results. Unlike L2 regularization, L1 regularization can preserve the details and reduce the noise effectively. Reconstruction is obtained through a restarted L1 regularization-based nonlinear conjugate gradient (re-L1-NCG) algorithm, which has been proven to be able to increase the computational speed with low memory consumption. The algorithm consists of inner and outer iterations. In the inner iteration, L1-NCG is used to obtain the L1-regularized results. In the outer iteration, the restarted strategy is used to increase the convergence speed of L1-NCG. To demonstrate the performance of re-L1-NCG in terms of spatial resolution, simulation and physical phantom studies with fluorescent targets located with different edge-to-edge distances were carried out. The reconstruction results show that the re-L1-NCG algorithm has the ability to resolve targets with an edge-to-edge distance of 0.1 cm at a depth of 1.5 cm, which is a significant improvement for FMT.

LS1 general planning and strategy for the LHC, LHC injectors

CERN Document Server

Foraz, K

2012-01-01

The goal of Long Shutdown 1 (LS1) is to perform the full maintenance of equipment, and the necessary consolidation and upgrade activities in order to ensure reliable LHC operation at nominal performance from mid 2014. LS1 not only concerns LHC but also its injectors. To ensure resources will be available an analysis is in progress to detect conflict/overload and decide what is compulsary, what we can afford, and what can be postponed to LS2. The strategy, time key drivers, constraints, and draft schedule will be presented here.

Cross-linkable liposomes stabilize a magnetic resonance contrast-enhancing polymeric fastener.

Science.gov (United States)

Smith, Cartney E; Kong, Hyunjoon

2014-04-08

Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads.

Non-stop training during LS1!

CERN Multimedia

HSE Unit

2013-01-01

The year 2013 is a busy year for the Safety Training team, who are seeing a dramatic increase in their activities during LS1. The Safety Training Service within the HSE Unit offers training courses all year round to people working on the CERN site who are exposed to a variety of potential hazards (e.g. chemical hazards, fire hazards, etc.) either because of the activities they perform (e.g. work in confined spaces or on machines) and/or their place of work (e.g. workshops, laboratories, underground areas, etc.).   LS1 has triggered an increase in the number of requests for training, mainly from people requiring to carry out work on the LHC. Indeed, in order to access the underground areas, it is obligatory to have taken certain safety courses such as the self-rescue mask or radiation protection training courses. Consequently, the number of training sessions and the number of people trained is currently twice what it was during the same period in 2012, with almost 4,600 people trained in 530 s...

Effects of liposome-adriamycin (L-ADM) and thermotherapy on glioma cells: an experimental study

OpenAIRE

Zheng-hua SHI; Jian-ning ZHANG

2013-01-01

Objective 　To observe the effects of liposome-adriamycin (L-ADM) and thermotherapy on proliferation and apoptosis of SWO-38 glioma cells. Methods 　The SWO-38 glioma cells were cultivated in vitro. The effects of thermotherapy (43℃), ADM chemotherapy, L-ADM chemotherapy, thermotherapy + ADM chemotherapy, and thermotherapy + L-ADM chemotherapy on the cell proliferation and apoptosis were observed. The working concentration of ADM and L-ADM, and the cell proliferation rate were determined by MTT...

Performance potential of the injectors after LS1

International Nuclear Information System (INIS)

Bartosik, H.; Carli, C.; Damerau, H.; Garoby, R.; Gilardoni, S.; Goddard, B.; Hancock, S.; Hanke, K.; Lombardi, A.; Mikulec, B.; Raginel, V.; Rumolo, G.; Shaposhnikova, E.; Vretenar, M.

2012-01-01

The main upgrades of the injector chain in the framework of the LIU Project will only be implemented in the second long shutdown (LS2), in particular the increase of the PSB-PS transfer energy to 2 GeV or the implementation of cures/solutions against instabilities/e-cloud effects etc. in the SPS. On the other hand, Linac4 will become available by the end of 2014. Until the end of 2015 it may replace Linac2 at short notice, taking 50 MeV protons into the PSB via the existing injection system but with reduced performance. Afterwards, the H - injection equipment will be ready and Linac4 could be connected for 160 MeV H - injection into the PSB during a prolonged winter shutdown before LS2. The anticipated beam performance of the LHC injectors after LS1 in these different cases is presented. Space charge on the PS flat-bottom will remain a limitation because the PSB-PS transfer energy will stay at 1.4 GeV. As a mitigation measure new RF manipulations are presented which can improve brightness for 25 ns bunch spacing, allowing for more than nominal luminosity in the LHC. (authors)

Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

Science.gov (United States)

Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

2011-01-01

Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the

Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives.

Science.gov (United States)

Scomparin, Anna; Florindo, Helena F; Tiram, Galia; Ferguson, Elaine L; Satchi-Fainaro, Ronit

2017-09-01

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination. Copyright © 2017 Elsevier B.V. All rights reserved.

LS1 Report: nearing the finish line

CERN Multimedia

Katarina Anthony

2014-01-01

The LS1 team will be popping the champagne next week, on Tuesday 27 May, celebrating the completion of the consolidation of the splices in the framework of the SMACC project.   A technician works on one of the final shunts during LS1. "It has been a long journey into the heart of the LHC, tackling over 27,000 shunts*," says Luca Bottura, TE-MSC Group leader. "We are happy that the final train has, at last, reached its rest station, and look forward to sending it on many new adventures," confirm Frédéric Savary, TE-MSC Large Magnet Facility Section leader, and Jean-Philippe Tock, SMACC Project leader. Also in the LHC, pressure tests in Sector 1-2 - the third sector to be tackled - are almost complete. The temperature in Sector 6-7 is around 100K and it will be accessible again from next week. As for the SPS, all the LSS1 beam elements excluding one monitor are back in position. Vacuum teams are now ...

Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults.

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Martin R Gaudinski

2018-01-01

Full Text Available VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb against the CD4-binding site of the HIV-1 envelope glycoprotein (Env that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor.This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccine Research Center (VRC at the National Institutes of Health (NIH Clinical Center (Bethesda, MD. The age range of the study volunteers was 21-50 years; 51% of study volunteers were male and 49% were female. Primary objectives were safety and tolerability of VRC01LS intravenous (IV infusions at 5, 20, and 40 mg/kg infused once, 20 mg/kg given three times at 12-week intervals, and subcutaneous (SC delivery at 5 mg/kg delivered once, or three times at 12-week intervals. Secondary objectives were pharmacokinetics (PK, serum neutralization activity, and development of antidrug antibodies. Enrollment began on November 16, 2015, and concluded on August 23, 2017. This report describes the safety data for the first 37 volunteers who received administrations of VRC01LS. There were no serious adverse events (SAEs or dose-limiting toxicities. Mild malaise and myalgia were the most common adverse events (AEs. There were six AEs assessed as possibly related to VRC01LS administration, and all were mild in severity and resolved during the study. PK data were modeled based on the first dose of VRC01LS in the first 25 volunteers to complete their schedule of evaluations. The mean (±SD serum concentration 12 weeks after one IV administration of 20 mg/kg or 40 mg/kg were 180 ± 43 μg/mL (n = 7 and 326 ± 35 μg/mL (n = 5, respectively. The mean (±SD serum concentration 12 weeks after one IV and SC administration of 5 mg/kg were 40 ± 3 μg/mL (n = 2 and 25 ± 5 μg/mL (n = 9, respectively. Over the 5-40 mg

Liposomes incorporating essential oil of Brazilian cherry (Eugenia uniflora L.): characterization of aqueous dispersions and lyophilized formulations.

Science.gov (United States)

Yoshida, P A; Yokota, D; Foglio, M A; Rodrigues, R A F; Pinho, S C

2010-01-01

Multilamellar liposomes incorporating essential oil of Brazilian cherry (Eugenia uniflora L.) leaves were produced by dry film hydration. Gas chromatography demonstrated the compounds found in the essential oil were effectively incorporated in the aqueous dispersions of liposomes. Differential scanning calorimetry analyses revealed the incorporation of the essential oil did not cause phase separation in the membrane structure; the gel-liquid crystalline transition temperature (main transition) remained the same despite the higher heterogeneity indicated by the transition peak broadening. Different cryoprotectors (sucrose and trehalose) were added to the liposomal formulations to be tested in their ability to protect the liposomal structure during the lyophilization. The morphological aspect of the lyophilized powders analysed by scanning electron microscopy showed significant differences among the samples with and without cryoprotectors. Fourier-transform infrared spectroscopy indicated the cryoprotectors interacted effectively with the polar heads of phospholipids in the bilayer. In terms of water absorption, trehalose was identified as a much more effective protector agent against it than sucrose. The cryoprotectors showed different degrees of effectiveness of preservation of the liposomal structure when the rehydration assays of lyophilized liposomes were carried out, as particle size measurements indicated a moderate process of fusion when the formulations with sucrose were rehydrated.

A fluorescent sensor based on dansyl-diethylenetriamine-thiourea conjugate: a through theoretical investigation

International Nuclear Information System (INIS)

Nguyen Khoa Hien; Nguyen Thi Ai Nhung; Duong Tuan Quang; Ho Quoc Dai; Nguyen Tien Trung

2015-01-01

A new dansyl-diethylenetriamine-thiourea conjugate (DT) for detection of Hg 2+ ions in aqueous solution has been theoretically designed and compared to our previously published results. The synthetic path, the optimized geometric structure and the characteristics of the DT were found by the theoretical calculations at the B3LYP/LanL2DZ level. Accordingly, the DT can react with Hg 2+ ion to form a product with quenched fluorescence. It is remarkable that the experimental results are in an excellent agreement with the theoretically evaluated data. (author)

The autoimmunity risk variant LYP-W620 cooperates with CSK in the regulation of TCR signaling.

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María Luisa de la Puerta

Full Text Available The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins.

Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

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Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

2009-01-01

Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

Rapid Quantification and Validation of Lipid Concentrations within Liposomes

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Carla B. Roces

2016-09-01

Full Text Available Quantification of the lipid content in liposomal adjuvants for subunit vaccine formulation is of extreme importance, since this concentration impacts both efficacy and stability. In this paper, we outline a high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD method that allows for the rapid and simultaneous quantification of lipid concentrations within liposomal systems prepared by three liposomal manufacturing techniques (lipid film hydration, high shear mixing, and microfluidics. The ELSD system was used to quantify four lipids: 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC, cholesterol, dimethyldioctadecylammonium (DDA bromide, and ᴅ-(+-trehalose 6,6′-dibehenate (TDB. The developed method offers rapidity, high sensitivity, direct linearity, and a good consistency on the responses (R2 > 0.993 for the four lipids tested. The corresponding limit of detection (LOD and limit of quantification (LOQ were 0.11 and 0.36 mg/mL (DMPC, 0.02 and 0.80 mg/mL (cholesterol, 0.06 and 0.20 mg/mL (DDA, and 0.05 and 0.16 mg/mL (TDB, respectively. HPLC-ELSD was shown to be a rapid and effective method for the quantification of lipids within liposome formulations without the need for lipid extraction processes.

Enhanced photodynamic efficacy of zinc phthalocyanine by conjugating to heptalysine.

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Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

2012-11-21

Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

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Eliot. P. Botosoa

2011-01-01

Full Text Available Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR. Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

Transport of S-cysteine conjugates in LL-PK1 cells and its role in toxicity

International Nuclear Information System (INIS)

Schaeffer, V.; Stevens, J.

1986-01-01

In order to study its role in S-cysteine conjugate toxicity, the transport of the nephrotoxic cysteine conjugate, S-1,2-dichlorovinyl-L-cysteine (L-DCVC), was investigated in the kidney cell line, LLC-PK1. When incubated with [ 35 S]-DCVC, accumulation of radioactivity within the cells was linear for at least 5 min with 92% of the 35 S present as unmetabolized L-DCVC. Kinetic analysis indicated two saturable uptake systems; Km = 6.8 μM and 1.6 mM; V/sub max/ = .048 and 1.4 nmol/min/mg protein. Both systems were Na + -independent and were inhibited by amino acid transport system L substrates but not substrates of systems A, ASC or organic anion transport. L-DCVC uptake at 5 μM and 500 μM was significantly greater in subconfluent cells than in confluent cultures by 5 and 2.8 fold, respectively. The presence of the non-toxic conjugates S-methyl-(SMC), S-ethyl-(SEC), S-benzyl-L- cysteine (SBC) and the D isomer of DCVC blocked the toxicity and inhibited the transport of L-DCVC in LLC-PK1 cells in the rank order of SBC > SEC congruent to D-DCVC > SMC. The metabolism of L-DCVC, previously shown to be required for cytotoxicity, was only slightly inhibited by these conjugates and did not correlate with their relative protection against toxicity. This study suggests that L-DCVC is transported into these cells by the system L transporter and that protection against toxicity by non-toxic S-cysteine conjugates is due to the inhibition of transport

Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

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Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

2017-12-15

Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct uptake mechanisms but similar intracellular processing of two different toll-like receptor ligand-peptide conjugates in dendritic cells.

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Khan, Selina; Bijker, Martijn S; Weterings, Jimmy J; Tanke, Hans J; Adema, Gosse J; van Hall, Thorbald; Drijfhout, Jan W; Melief, Cornelis J M; Overkleeft, Hermen S; van der Marel, Gijsbert A; Filippov, Dmitri V; van der Burg, Sjoerd H; Ossendorp, Ferry

2007-07-20

Covalent conjugation of Toll-like receptor ligands (TLR-L) to synthetic antigenic peptides strongly improves antigen presentation in vitro and T lymphocyte priming in vivo. These molecularly well defined TLR-L-peptide conjugates, constitute an attractive vaccination modality, sharing the peptide antigen and a defined adjuvant in one single molecule. We have analyzed the intracellular trafficking and processing of two TLR-L conjugates in dendritic cells (DCs). Long synthetic peptides containing an ovalbumin cytotoxic T-cell epitope were chemically conjugated to two different TLR-Ls the TLR2 ligand, Pam(3)CysSK(4) (Pam) or the TLR9 ligand CpG. Rapid and enhanced uptake of both types of TLR-L-conjugated peptide occurred in DCs. Moreover, TLR-L conjugation greatly enhanced antigen presentation, a process that was dependent on endosomal acidification, proteasomal cleavage, and TAP translocation. The uptake of the CpG approximately conjugate was independent of endosomally-expressed TLR9 as reported previously. Unexpectedly, we found that Pam approximately conjugated peptides were likewise internalized independently of the expression of cell surface-expressed TLR2. Further characterization of the uptake mechanisms revealed that TLR2-L employed a different uptake route than TLR9-L. Inhibition of clathrin- or caveolin-dependent endocytosis greatly reduced uptake and antigen presentation of the Pam-conjugate. In contrast, internalization and antigen presentation of CpG approximately conjugates was independent of clathrin-coated pits but partly dependent on caveolae formation. Importantly, in contrast to the TLR-independent uptake of the conjugates, TLR expression and downstream TLR signaling was required for dendritic cell maturation and for priming of naïve CD8(+) T-cells. Together, our data show that targeting to two distinct TLRs requires distinct uptake mechanism but follows similar trafficking and intracellular processing pathways leading to optimal antigen

Study of the following decays: K{sub l,s} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -}; Etude des desintegrations K{sub l,s} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -}

Energy Technology Data Exchange (ETDEWEB)

Cogan, J

2001-12-01

The study of the K{sub L,S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} decay modes in the NA48 experiment at CERN is presented in this thesis. Using the full data samples collected in 1998 and 1999, 1285 {+-} 37 events K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} have been extracted over a background of 41 events. The measured branching ratio is: BR(K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[3,16{+-}0,09(stat.){+-}0,16(syst.)] x 10{sup -7}. Concerning the K{sub S} mode, a signal of 768 {+-} 28 candidates has been observed over a negligible background. The obtained branching ratio is: BR(K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[4,28{+-}0,18(stat.){+-}0,26(syst.)] x 10{sup -5}. Both results are in very good agreement with the values predicted by phenomenological models where the processes K{sub L,S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} are described in terms of inner Bremsstrahlung and direct emission contributions. In the K{sub L} mode, the presence of two components with opposed CP states leads to a large asymmetry A in the distribution of the angle {phi} between the decay planes of the two pions and the two electrons. The detailed analysis of the K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} mode ends up to a non-zero value of the asymmetry with more than 4 standard deviations: A(K{sub L} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[13,8{+-}2,8(stat.){+-}2,3(syst.)]%. This result is a clear manifestation of CP violation in this channel. The large value of this asymmetry, in excellent agreement with theoretical prediction, accounts for CP violation in the K{sup 0}-K-bar{sup 0} mixing. Furthermore, it was verified that in the K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -} mode which is dominated by the inner Bremsstrahlung component, the asymmetry is compatible with zero: A(K{sub S} {yields} {pi}{sup +}{pi}{sup -}e{sup +}e{sup -})=[-0,8{+-}3,6(stat.){+-}1,2(syst.)]%. (author)

DDA/TDB liposomes containing soluble Leishmania major antigens induced a mixed Th1/Th2 immune response in BALB/c mice

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Mansure Hojatizade

2017-04-01

Full Text Available Objective(s: Leishmaniasis is a complex parasitic disease that represents a major public health problem. Despite numerous attempts over the past decades, yet there is no effective vaccine against human leishmaniasis probably due to the lack of suitable adjuvants. In this study, a first generation liposomal-based Leishmania vaccine was developed using soluble Leishmania major antigens (SLA and á, Ü-trehalose6, 6'-dibehenat (TDB as an immunostimulatory adjuvant. In this liposome structure, the cationic lipid Dimethyldioctadecylammonium (DDA provides intrinsic adjuvant activity and cholesterol was added as a membrane stabilizer. Liposomes containing SLA were prepared.Materials and Methods: BALB/c mice were subcutaneously (sc immunized with Lip (DDA/TDB/CHOL-SLA+, Lip (DDA/TDB-SLA+, Lip (DDA-SLA+, Lip (DDA/CHOL-SLA+, SLA or Tris-HCl buffer. Immunization was done every two weeks for three weeks. The immunized mice were then challenged sc in the left footpad with 1×106 stationary phase L. major promastigotes (50 ìl, at 2 weeks after last booster injection.Results: mice immunized with any of the liposomal formulations containing SLA (Lip-SLA+, substantially increased footpad swelling and parasite loads of foot and spleen with no significant difference compared to Tris-HCl buffer or SLA alone. Lip-SLA+ formulations induced a mixed Th1/Th2 immune response characterized by IFN-ã and IL-4 production as well as high levels of IgG1 anti-Leishmania antibody. Conclusion: immunization with liposomes containing DDA and/or TDB in combination with SLA induces a mixed Th1/Th2 immune response and is not an appropriate strategy for preferential induction of a Th1 response and protection against leishmaniasis.

L-Cysteine conjugated poly L-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissues in vivo.

Science.gov (United States)

Mishra, Brijeshkunvar J; Kaul, Ankur; Trivedi, Piyush

2015-02-01

Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

International Symposium: “Scientific School of L.S. Vygotsky: Traditions and Innovations” and International ISCAR Summer University for PhD Students

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Baykovskaya N.A.,

2016-12-01

Full Text Available The article represents a brief report on the work of the International Symposium: «Scientific School of L.S. Vygotsky: Traditions and Innovations» and VI th International ISCAR Summer University for PhD Students and young scholars, that were held in Moscow State University of Psychology & Education on June, 28 — July, 3 in 2016 in commemoration of the 120th anniversary of the great Russian psychologist L.S. Vygotsky. The main goals of the events organised by MSUPE include: analysis of the basic principles and the system of concepts of L.S. Vygotsky’s scientific school, discussion of the current state and the prospect for the development of the cultural-historical theory in Russia and abroad, integration of the ideas of the cultural-historical psychology and activity approach in various kinds of social and educational practices, as well as conducting research in the international scientific space. Symposium gathered the world’s leading experts and young scholars in the field of cultural-historical theory and activity approach from 19 countries, including United Kingdom, Australia, Switzerland, Greece, Brasil and USA.

Detector Plans for LS1

Energy Technology Data Exchange (ETDEWEB)

Nessi, M [European Organization for Nuclear Research, Geneva (Switzerland)

2012-07-01

All experiments plan an effective usage of the LS1 shutdown period. After three years of running they will go through a consolidation phase, mostly to fix problems that have emerged over time, like single points of failure in the infrastructure, failures of low voltage power supplies and optical links. Upgrades of some detector components will start, mainly related to the beam pipe, the innermost tracker elements and the trigger system. Detector components, which had to be staged for cost reasons in 2003, will then enter into the detector setup. The goal is to be fully ready for the new energy regime at nominal luminosity.

Biotinylated liposomes as potential carriers for the oral delivery of insulin.

Science.gov (United States)

Zhang, Xingwang; Qi, Jianping; Lu, Yi; He, Wei; Li, Xiaoyang; Wu, Wei

2014-01-01

This study aimed to explore biotinylated liposomes (BLPs) as novel carriers to enhance the oral delivery of insulin. Biotinylation was achieved by incorporating biotin-conjugated phospholipids into the liposome membranes. A significant hypoglycemic effect and enhanced absorption were observed after treating diabetic rats with the BLPs with a relative bioavailability of 12.09% and 8.23%, based on the measurement of the pharmacologic effect and the blood insulin level, respectively; this achieved bioavailability was approximately double that of conventional liposomes. The significance of the biotinylation was confirmed by the facilitated absorption of the BLPs through receptor-mediated endocytosis, as well as by the improved physical stability of the liposomes. Increased cellular uptake and quick gastrointestinal transport further verified the ability of the BLPs to enhance absorption. These results provide a proof of concept that BLPs can be used as potential carriers for the oral delivery of insulin. Diabetes remains a major source of mortality in the Western world, and advances in its management are expected to have substantial socioeconomic impact. In this paper, biotinylated liposomes were utilized as carriers of insulin for local delivery, demonstrating the feasibility of this approach in a rat model. © 2014.

LS1 Report: Handing in the ATLAS keys

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Antonella Del Rosso, Katarina Anthony

2014-01-01

After completing more than 250 work packages concerning the whole detector and experimental site, the ATLAS and CERN teams involved with LS1 operations are now wrapping things up before starting the commissioning phase in preparation for the LHC restart. The giant detector is now more efficient, safer and even greener than ever thanks to the huge amount of work carried out over the past two years.   Cleaning up the ATLAS cavern and detector in preparation for Run 2. Hundreds of people, more than 3000 certified interventions, huge and delicate parts of the detector completely refurbished: the ATLAS detector that will take data during Run 2 is a brand new machine, which will soon be back in the hands of the thousands of scientists who are preparing for the high-energy run of the LHC accelerator. “During LS1, we have upgraded the detector’s basic infrastructure and a few of its sub-detectors,” explains Beniamino Di Girolamo, ATLAS Technical Coordinator. &...

Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

Science.gov (United States)

Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

2012-01-01

Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

Galen's Anxious Patients: Lypē as Anxiety Disorder.

Science.gov (United States)

Mattern, Susan P

2016-01-01

Galen describes a syndrome he associates with an emotion called lypē, with specific symptoms and a course that may lead to humoral imbalance, disease, and death. Lypē is an emotion that encompasses distress at a loss, as the death of a close friend or the destruction of one's books by fire; but Galen also associates it with chronic worry about a future threat, and a physiology between the emotions of worry and fear (that is, 'anxiety'). Lypē can cause a progressive syndrome characterised by insomnia, fever, pallor, and weight loss that can kill patients or degenerate into psychotic illness. This syndrome can be described in modern terms as an anxiety disorder.

Optimization and modeling of the remote loading of luciferin into liposomes.

Science.gov (United States)

Hansen, Anders Højgaard; Lomholt, Michael A; Hansen, Per Lyngs; Mouritsen, Ole G; Arouri, Ahmad

2016-07-11

We carried out a mechanistic study to characterize and optimize the remote loading of luciferin into preformed liposomes of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPC/DPPG) 7:3 mixtures. The influence of the loading agent (acetate, propionate, butyrate), the metal counterion (Na(+), K(+), Ca(+2), Mg(+2)), and the initial extra-liposomal amount of luciferin (nL(add)) on the luciferin Loading Efficiency (LE%) and luciferin-to-lipid weight ratio, i.e., Loading Capacity (LC), in the final formulation was determined. In addition, the effect of the loading process on the colloidal stability and phase behavior of the liposomes was monitored. Based on our experimental results, a theoretical model was developed to describe the course of luciferin remote loading. It was found that the highest luciferin loading was obtained with magnesium acetate. The use of longer aliphatic carboxylates or inorganic proton donors pronouncedly reduced luciferin loading, whereas the effect of the counterion was modest. The remote-loading process barely affected the colloidal stability and drug retention of the liposomes, albeit with moderate luciferin-induced membrane perturbations. The correlation between luciferin loading, expressed as LE% and LC, and nL(add) was established, and under our conditions the maximum LC was attained using an nL(add) of around 2.6μmol. Higher amounts of luciferin tend to pronouncedly perturb the liposome stability and luciferin retention. Our theoretical model furnishes a fair quantitative description of the correlation between nL(add) and luciferin loading, and a membrane permeability coefficient for uncharged luciferin of 1×10(-8)cm/s could be determined. We believe that our study will prove very useful to optimize the remote-loading strategies of moderately polar carboxylic acid drugs in general. Copyright © 2016 Elsevier B.V. All rights reserved.

Apoptosis- and differentiation-inducing activities of jacaric acid, a conjugated linolenic acid isomer, on human eosinophilic leukemia EoL-1 cells.

Science.gov (United States)

Liu, Wai-Nam; Leung, Kwok-Nam

2014-11-01

Conjugated linolenic acids (CLNAs) are a group of naturally occurring positional and geometrical isomers of the C18 polyunsaturated essential fatty acid, linolenic acid (LNA), with three conjugated double bonds (C18:3). Although previous research has demonstrated the growth-inhibitory effects of CLNA on a wide variety of cancer cell lines in vitro, their action mechanisms and therapeutic potential on human myeloid leukemia cells remain poorly understood. In the present study, we found that jacaric acid (8Z,10E,12Z-octadecatrienoic acid), a CLNA isomer which is present in jacaranda seed oil, inhibited the in vitro growth of human eosinophilic leukemia EoL-1 cells in a time- and concentration-dependent manner. Mechanistic studies showed that jacaric acid triggered cell cycle arrest of EoL-1 cells at the G0/G1 phase and induced apoptosis of the EoL-1 cells, as measured by the Cell Death Detection ELISAPLUS kit, Annexin V assay and JC-1 dye staining. Notably, the jacaric acid-treated EoL-1 cells also underwent differentiation as revealed by morphological and phenotypic analysis. Collectively, our results demonstrated the capability of jacaric acid to inhibit the growth of EoL-1 cells in vitro through triggering cell cycle arrest and by inducing apoptosis and differentiation of the leukemia cells. Therefore, jacaric acid might be developed as a potential candidate for the treatment of certain forms of myeloid leukemia with minimal toxicity and few side effects.

Contribution à la formulation et à l'évaluation de liposomes d'ATP

OpenAIRE

Vincourt-Vitse, Véronique,

2012-01-01

ATP liposome incorporating hepatic ligands may contribute to improve the energetic status of the liver graft. In a first phase of development, it has been emphasized the great need of stabilizing the liposome (i) and of validating a cellular model with an altered energetic status in order to test the formulations of interest. To provide a stable liposomal preparation, different strategies have been carried out to freeze-dry liposome with or without ATP. Sucrose and trehalose better stabilize ...

Construction of a Liposome Dialyzer for preparation of high-value, small-volume liposome formulations

Science.gov (United States)

Adamala, Katarzyna; Engelhart, Aaron E.; Kamat, Neha P.; Jin, Lin; Szostak, Jack W.

2016-01-01

The liposome dialyzer is a small-volume equilibrium dialysis device, built from commercially available materials, that is designed for rapid exchange of small volumes of an extraliposomal reagent pool against a liposome preparation. The dialyzer is prepared by modification of commercially available dialysis cartridges and consists of a reactor with two 300 µL chambers and a 1.56 cm2 dialysis surface area. The dialyzer is prepared in three stages: 1) disassembly of dialysis cartridges to obtain required parts; 2) assembly of the dialyzer; and 3) sealing the dialyzer with epoxy. Preparation of the dialyser takes about 1.5 h, not including overnight epoxy curing. Each round of dialysis takes 1–24 h, depending on the analyte and membrane employed. We previously used the dialyzer for small-volume nonenzymatic RNA synthesis reactions inside fatty acid vesicles. In this protocol, we demonstrate other applications, including removal of unencapsulated calcein from vesicles, remote loading, and vesicle microscopy. PMID:26020615

Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

Directory of Open Access Journals (Sweden)

Irma Pujol-Autonell

Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

Czech Academy of Sciences Publication Activity Database

Škorpilová, Ludmila; Rimpelová, S.; Jurášek, M.; Buděšínský, Miloš; Lokajová, Jana; Effenberg, R.; Slepička, P.; Ruml, T.; Kmoníčková, Eva; Drašar, P. B.; Wimmer, Zdeněk

2017-01-01

Roč. 13, JUL 4 (2017), s. 1316-1324 ISSN 1860-5397 R&D Projects: GA MŠk LD15012; GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 ; RVO:61388963 ; RVO:68378041 Keywords : BODIPY conjugates * Cancer targeting * Drug delivery * Liposomes * Natural compounds * Sesquiterpene lactone trilobolide Subject RIV: CC - Organic Chemistry ; FR - Pharmacology ; Medidal Chemistry (UEM-P) OBOR OECD: Organic chemistry ; Pharmacology and pharmacy (UEM-P) Impact factor: 2.337, year: 2016

Detectors plans for LS1

International Nuclear Information System (INIS)

Nessi, M.

2012-01-01

All experiments plan an effective usage of the LS1 shutdown period. After three years of running they will go through a consolidation phase, mostly to fix problems that have emerged over time, like single points of failure in the infrastructure, failures of low-voltage power supplies and optical links. Upgrades of some detector components will start, mainly related to the beam pipe, the innermost tracker elements and the trigger system. Detector components, which had to be staged for cost reasons in 2003, will then enter into the detector setup. The goal is to be fully ready for the new energy regime at nominal luminosity. This article reviews the planned maintenance and modification works for ATLAS, CMS, LHCb and ALICE experiments. (author)

Influence of the Encapsulation Efficiency and Size of Liposome on the Oral Bioavailability of Griseofulvin-Loaded Liposomes

Directory of Open Access Journals (Sweden)

Sandy Gim Ming Ong

2016-08-01

Full Text Available The objective of the present study was to investigate the influence of the encapsulation efficiency and size of liposome on the oral bioavailability of griseofulvin-loaded liposomes. Griseofulvin-loaded liposomes with desired characteristics were prepared from pro-liposome using various techniques. To study the effect of encapsulation efficiency, three preparations of griseofulvin, namely, griseofulvin aqueous suspension and two griseofulvin-loaded liposomes with different amounts of griseofulvin encapsulated [i.e., F1 (32% and F2(98%], were administered to rats. On the other hand, to study the effect of liposome size, the rats were given three different griseofulvin-loaded liposomes of various sizes, generated via different mechanical dispersion techniques [i.e., FTS (142 nm, MS (357 nm and NS (813 nm], but with essentially similar encapsulation efficiencies (about 93%. Results indicated that the extent of bioavailability of griseofulvin was improved 1.7–2.0 times when given in the form of liposomes (F1 compared to griseofulvin suspension. Besides that, there was an approximately two-fold enhancement of the extent of bioavailability following administration of griseofulvin-loaded liposomes with higher encapsulation efficiency (F2, compared to those of F1. Also, the results showed that the extent of bioavailability of liposomal formulations with smaller sizes were higher by approximately three times compared to liposomal formulation of a larger size. Nevertheless, a further size reduction of griseofulvin-loaded liposome (≤400 nm did not promote the uptake or bioavailability of griseofulvin. In conclusion, high drug encapsulation efficiency and small liposome size could enhance the oral bioavailability of griseofulvin-loaded liposomes and therefore these two parameters deserve careful consideration during formulation.

Cellular Injury of Cardiomyocytes during Hepatocyte Growth Factor Gene Transfection with Ultrasound-Triggered Bubble Liposome Destruction

Directory of Open Access Journals (Sweden)

Kazuo Komamura

2011-01-01

Full Text Available We transfected naked HGF plasmid DNA into cultured cardiomyocytes using a sonoporation method consisting of ultrasound-triggered bubble liposome destruction. We examined the effects on transfection efficiency of three concentrations of bubble liposome (1×106, 1×107, 1×108/mL, three concentrations of HGF DNA (60, 120, 180 μg/mL, two insonification times (30, 60 sec, and three incubation times (15, 60, 120 min. We found that low concentrations of bubble liposome and low concentrations of DNA provided the largest amount of the HGF protein expression by the sonoporated cardiomyocytes. Variation of insonification and incubation times did not affect the amount of product. Following insonification, cardiomyocytes showed cellular injury, as determined by a dye exclusion test. The extent of injury was most severe with the highest concentration of bubble liposome. In conclusion, there are some trade-offs between gene transfection efficiency and cellular injury using ultrasound-triggered bubble liposome destruction as a method for gene transfection.

Detection of peritoneal dissemination with near-infrared fluorescence laparoscopic imaging using a liposomal formulation of a synthesized indocyanine green liposomal derivative.

Science.gov (United States)

Hoshino, Isamu; Maruyama, Tetsuro; Fujito, Hiromichi; Tamura, Yutaka; Suganami, Akiko; Hayashi, Hideki; Toyota, Taro; Akutsu, Yasunori; Murakami, Kentaro; Isozaki, Yuka; Akanuma, Naoki; Takeshita, Nobuyoshi; Toyozumi, Takeshi; Komatsu, Aki; Matsubara, Hisahiro

2015-03-01

Although conventional staging laparoscopy (SL) has improved the diagnostic accuracy of peritoneal dissemination, novel technology is needed to increase the sensitivity of SL. We herein describe a new imaging method employing near-infrared (NIR) fluorescence imaging using a liposomal synthesized indocyanine green (ICG) liposomal derivative, LP-ICG-C18. LP-ICG-C18 is a NIR-photoactivating probe in which an ICG fluorophore is covalently conjugated with a phospholipid moiety. Nude mice were intraperitoneally injected with gastric cancer cells. Twelve days later, the mice were given intravenous injections of LP-ICG-C18 at a dose of 0.15 mg/kg. A NIR imaging system was used to identify the disseminated tumors. The disseminated nodules in mice were detected without any difficulties. Disseminated tumor nodules were collected from mice with or without injections of liposomal formulation and were transferred into the swine peritoneal cavity. The nodules in the swine peritoneal cavity were clearly and promptly defined by the NIR imaging system. NIR-fluorescing liposomal probes can effectively target peritoneal disseminated tumors and can be easily detected by a NIR imaging system. These results warrant future clinical trials of our imaging system and may contribute to a more precise diagnosis and therapeutic approach for gastric cancer patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Simultant encapsulation of vitamin C and beta-carotene in sesame (Sesamum indicum l.) liposomes

Science.gov (United States)

Hudiyanti, D.; Fawrin, H.; Siahaan, P.

2018-04-01

In this study sesame liposomes were used to encapsulate both vitamin C and beta-carotene simultaneously. Liposomes were prepared with addition of cholesterol. The encapsulation efficiency (EE) of sesame liposomes for vitamin C in the present of beta-carotene was 77%. The addition of cholesterol increased the encapsulation efficiency. The highest encapsulation efficiency was 89% obtained in liposomes with 10% and 20% cholesterol. Contrary to that, the highest beta-carotene encapsulation efficiency of 78%, was found in the sesame liposomes prepared without the added cholesterol. Results showed that sesame liposomes can be used to encapsulate beta-carotene and vitamin C simultaneously. When beta-carotene and vitamin C were encapsulated concurrently, cholesterol intensified the efficiency of vitamin C encapsulation on the contrary it diminished the efficiency of beta-carotene encapsulation.

Calcipotriol delivery into the skin with PEGylated liposomes

DEFF Research Database (Denmark)

Knudsen, Nina Østergaard; Rønholt, Stine; Salte, Ragnhild Djønne

2012-01-01

The d-vitamin analogue calcipotriol is commonly used for topical treatment of psoriasis, but skin penetration is required for calcipotriol to reach its pharmacological target: the keratinocytes in the lower epidermis. Liposomes can enhance the delivery of drugs into the skin, but a major challenge...... of the liposomes and the ability to deliver membrane-intercalated calcipotriol into the skin. Inclusion of 0.5, l and 5mol% PEG-DSPE in the membrane enhanced the colloidal stability of the liposomes without compromising the delivery of calcipotriol from the vehicle into excised pig skin. Calcipotriol...... to large multilamellar vesicles, indicating that the liposomes to some extent migrate as intact vesicles into the stratum corneum. However, calcipotriol penetrated the skin better than the lipid component of the liposomes, suggesting that at least a fraction of the drug is released from the liposomes...

Launch of new e-learning course “Safety during LS1”

CERN Multimedia

HSE Unit

2013-01-01

After 3 years of activity, the LHC and the rest of the accelerator chain have been shut down for about 2 years (from February 2013 to December 2014) due to maintenance and upgrade work, on the surface as well as underground.   CERN has developed a new e-learning course related to this Long Shutdown period (LS1) so as to provide all the collaborators working in the LS1 area with accurate security-oriented information. The objectives of this new course are to: Present LS1 and its context, Identify CERN facilities’ major risks, Identify the main risks associated with our co-activities, Explain how safety issues are being handled at CERN, Present all the basic safety measures to be respected, Present all emergency and rescue instructions. The course is available via the e-learning SIR application. It is compulsory for all newcomers at CERN, along with the “CERN Safety Introduction” training. It is also highly recommended that people who were already w...

A gene encoding an abscisic acid biosynthetic enzyme (LsNCED4) collocates with the high temperature germination locus Htg6.1 in lettuce (Lactuca sp.).

Science.gov (United States)

Argyris, Jason; Truco, María José; Ochoa, Oswaldo; McHale, Leah; Dahal, Peetambar; Van Deynze, Allen; Michelmore, Richard W; Bradford, Kent J

2011-01-01

Thermoinhibition, or failure of seeds to germinate when imbibed at warm temperatures, can be a significant problem in lettuce (Lactuca sativa L.) production. The reliability of stand establishment would be improved by increasing the ability of lettuce seeds to germinate at high temperatures. Genes encoding germination- or dormancy-related proteins were mapped in a recombinant inbred line population derived from a cross between L. sativa cv. Salinas and L. serriola accession UC96US23. This revealed several candidate genes that are located in the genomic regions containing quantitative trait loci (QTLs) associated with temperature and light requirements for germination. In particular, LsNCED4, a temperature-regulated gene in the biosynthetic pathway for abscisic acid (ABA), a germination inhibitor, mapped to the center of a previously detected QTL for high temperature germination (Htg6.1) from UC96US23. Three sets of sister BC(3)S(2) near-isogenic lines (NILs) that were homozygous for the UC96US23 allele of LsNCED4 at Htg6.1 were developed by backcrossing to cv. Salinas and marker-assisted selection followed by selfing. The maximum temperature for germination of NIL seed lots with the UC96US23 allele at LsNCED4 was increased by 2-3°C when compared with sister NIL seed lots lacking the introgression. In addition, the expression of LsNCED4 was two- to threefold lower in the former NIL lines as compared to expression in the latter. Together, these data strongly implicate LsNCED4 as the candidate gene responsible for the Htg6.1 phenotype and indicate that decreased ABA biosynthesis at high imbibition temperatures is a major factor responsible for the increased germination thermotolerance of UC96US23 seeds.

Propargylamine-isothiocyanate reaction: efficient conjugation chemistry in aqueous media

DEFF Research Database (Denmark)

Viart, Helene Marie-France; Larsen, T. S.; Tassone, Chiara

2014-01-01

A coupling reaction between secondary propargyl amines and isothiocyanates in aqueous media is described. The reaction is high-yielding and affords cyclized products within 2-24 h. A functionalized ether lipid was synthesized in 8 steps, formulated as liposomes with POPC and conjugated to FITC un...

Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese.

Science.gov (United States)

Cui, H Y; Wu, J; Lin, L

2016-08-01

Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome-entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential (-58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4°C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Liposome distribution after intravenous and selective intraarterial infusion in dogs

International Nuclear Information System (INIS)

Wright, K.C.; Kasi, L.P.; Jahns, M.S.; Hashimoto, S.; Wallace, S.

1990-01-01

In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels

Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection.

Science.gov (United States)

Feng, Liangzhu; Tao, Danlei; Dong, Ziliang; Chen, Qian; Chao, Yu; Liu, Zhuang; Chen, Meiwan

2017-05-01

Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin. Copyright © 2016. Published by Elsevier Ltd.

Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro.

Science.gov (United States)

Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel J; Kalle, Wouter H J

2005-06-01

Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.

Construction of a liposome dialyzer for the preparation of high-value, small-volume liposome formulations.

Science.gov (United States)

Adamala, Katarzyna; Engelhart, Aaron E; Kamat, Neha P; Jin, Lin; Szostak, Jack W

2015-06-01

The liposome dialyzer is a small-volume equilibrium dialysis device, built from commercially available materials, that is designed for the rapid exchange of small volumes of an extraliposomal reagent pool against a liposome preparation. The dialyzer is prepared by modification of commercially available dialysis cartridges (Slide-A-Lyzer cassettes), and it consists of a reactor with two 300-μl chambers and a 1.56-cm(2) dialysis surface area. The dialyzer is prepared in three stages: (i) disassembling the dialysis cartridges to obtain the required parts, (ii) assembling the dialyzer and (iii) sealing the dialyzer with epoxy. Preparation of the dialyzer takes ∼1.5 h, not including overnight epoxy curing. Each round of dialysis takes 1-24 h, depending on the analyte and membrane used. We previously used the dialyzer for small-volume non-enzymatic RNA synthesis reactions inside fatty acid vesicles. In this protocol, we demonstrate other applications, including removal of unencapsulated calcein from vesicles, remote loading and vesicle microscopy.

Structural properties of liposomes from digital holographic microscopy

Science.gov (United States)

Di Maio, Isabelle L.; Carl, Daniel; Langehanenberg, Patrik; Valenzuela, Stella M.; Battle, Andrew R.; Al Khazaaly, Sabah; Killingsworth, Murray; Kemper, Bjorn; von Bally, Gert; Martin, Donald K.

2006-01-01

We have constructed liposomes from L alpha Phosphatidylcholine (PC) lipids, which are biomimetic lipids similar to those present in the membranes of mammalian cells. We propose an advance in the use of liposomes, such as for drug delivery, to incorporate into the liposomal membranes transport proteins that have been extracted from the lipid membranes of mammalian cells. In this paper, we describe the usage of a novel optical microscope to characterize the nanomechanical properties of these liposomes. We have applied the technique of digital holographic microscopy, using an instrument recently developed at the University of Münster, Germany. This system enabled us to measure quantitatively the structural changes in liposomes. We have investigated the deformations of these biomimetic lipids comprising these liposomes by applying osmotic stresses, in order to gain insight into the membrane environment prior to incorporation of cloned membrane transport proteins. This control of the nanomechanical properties is important in the stresses transmitted to mechanosensitive ion channels that we have incorporated into the liposomal membranes. These liposomes provide transporting vesicles that respond to mechanical stresses, such as those that occur during implantation.

Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

OpenAIRE

Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

1988-01-01

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time interva...

Multiple polysaccharide-drug complex-loaded liposomes: A unique strategy in drug loading and cancer targeting.

Science.gov (United States)

Ruttala, Hima Bindu; Ramasamy, Thiruganesh; Gupta, Biki; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2017-10-01

In the present study, a unique strategy was developed to develop nanocarriers containing multiple therapeutics with controlled release characteristics. In this study, we demonstrated the synthesis of dextran sulfate-doxorubicin (DS-DOX) and alginate-cisplatin (AL-CIS) polymer-drug complexes to produce a transferrin ligand-conjugated liposome. The targeted nanoparticles (TL-DDAC) were nano-sized and spherical. The targeted liposome exhibited a specific receptor-mediated endocytic uptake in cancer cells. The enhanced cellular uptake of TL-DDAC resulted in a significantly better anticancer effect in resistant and sensitive breast cancer cells compared to that of the free drugs. Specifically, DOX and CIS at a molar ratio of 1:1 exhibited better therapeutic performance compared to that of other combinations. The combination of an anthracycline-based topoisomerase II inhibitor (DOX) and a platinum compound (CIS) resulted in significantly higher cell apoptosis (early and late) in both types of cancer cells. In conclusion, treatment with DS-DOX and AL-CIS based combination liposomes modified with transferrin (TL-DDAC) was an effective cancer treatment strategy. Further investigation in clinically relevant animal models is warranted to prove the therapeutic efficacy of this unique strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Liposomal Bupivacaine for Pain Control After Anterior Cruciate Ligament Reconstruction: A Prospective, Double-Blinded, Randomized, Positive-Controlled Trial.

Science.gov (United States)

Premkumar, Ajay; Samady, Heather; Slone, Harris; Hash, Regina; Karas, Spero; Xerogeanes, John

2016-07-01

Local anesthetics are commonly administered into surgical sites as a part of multimodal pain control regimens. Liposomal bupivacaine is a novel formulation of bupivacaine designed for slow diffusion of a single dose of local anesthetic over a 72-hour period. While early results are promising in various settings, no studies have compared pain management regimens containing liposomal bupivacaine to traditional regimens in patients undergoing anterior cruciate ligament (ACL) reconstruction. To evaluate liposomal bupivacaine in comparison with 0.25% bupivacaine hydrochloride (HCl) for pain control after ACL reconstruction. Randomized controlled trial; Level of evidence, 1. A total of 32 adult patients undergoing primary ACL reconstruction with a soft tissue quadriceps tendon autograft between July 2014 and March 2015 were enrolled. All patients received a femoral nerve block immediately before surgery. Patients then received either a 40-mL suspension of 20 mL Exparel (1 vial of bupivacaine liposome injectable suspension) and 20 mL 0.9% injectable saline or 20 mL 0.5% bupivacaine HCl and 20 mL 0.9% injectable saline, which was administered into the graft harvest site and portal sites during surgery. Patients were given either a postoperative smartphone application or paper-based journal to record data for 1 week after ACL reconstruction. Of the 32 patients recruited, 29 patients were analyzed (90.6%). Two patients were lost to follow-up, and 1 was excluded because of a postoperative hematoma. There were no statistically significant differences in postoperative pain, medication use, pain location, recovery room time, or mobility between the 2 study groups. There were comparable outcomes with 0.25% bupivacaine HCl at a 200-fold lower cost than liposomal bupivacaine. This study does not support the widespread use of liposomal bupivacaine for pain control after ACL reconstruction in the setting of a femoral nerve block. ClinicalTrials.gov NCT02189317. © 2016 The Author(s).

Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer.

Science.gov (United States)

Zhang, Rui; Song, Xuejiao; Liang, Chao; Yi, Xuan; Song, Guosheng; Chao, Yu; Yang, Yu; Yang, Kai; Feng, Liangzhu; Liu, Zhuang

2017-09-01

Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within CAT@Pt (IV)-liposome shows retained and well-protected enzyme activity, and is able to trigger decomposition of H 2 O 2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of CAT@Pt (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such CAT@Pt (IV)-liposome nanoparticles. Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment. Copyright © 2017. Published by Elsevier Ltd.

PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

Science.gov (United States)

Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

2017-08-07

A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Lactobacillus salivarius Ls-33 on fecal microbiota in obese adolescents.

Science.gov (United States)

Larsen, Nadja; Vogensen, Finn K; Gøbel, Rikke Juul; Michaelsen, Kim F; Forssten, Sofia D; Lahtinen, Sampo J; Jakobsen, Mogens

2013-12-01

This study is a part of the clinical trials with probiotic bacterium Lactobacillus salivarius Ls-33 conducted in obese adolescents. Previously reported clinical studies showed no effect of Ls-33 consumption on the metabolic syndrome in the subject group. The aim of the study was to investigate the impact of L. salivarius Ls-33 on fecal microbiota in obese adolescents. The study was a double-blinded intervention with 50 subjects randomized to intake of L. salivarius Ls-33 or placebo for 12 weeks. The fecal microbiota was assessed by real-time quantitative PCR before and after intervention. Concentrations of fecal short chain fatty acids were determined using gas chromatography. Ratios of Bacteroides-Prevotella-Porphyromonas group to Firmicutes belonging bacteria, including Clostridium cluster XIV, Blautia coccoides_Eubacteria rectale group and Roseburia intestinalis, were significantly increased (p ≤ 0.05) after administration of Ls-33. The cell numbers of fecal bacteria, including the groups above as well as Clostridium cluster I, Clostridium cluster IV, Faecalibacterium prausnitzii, Enterobacteriaceae, Enterococcus, the Lactobacillus group and Bifidobacterium were not significantly altered by intervention. Similarly, short chain fatty acids remained unaffected. L. salivarius Ls-33 might modify the fecal microbiota in obese adolescents in a way not related to metabolic syndrome. NCT 01020617. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Biological activity of liposomal vanillin.

Science.gov (United States)

Castan, Leniher; Del Toro, Grisel; Fernández, Adolfo A; González, Manuel; Ortíz, Emilia; Lobo, Daliana

2013-06-01

This article presents a study of vanillin encapsulation inside multilamellar liposomes, with emphasis on the evaluation of antioxidant activity, the hemolytic effect, and the antisickling properties of these products. Egg phosphatidylcholine-cholesterol and egg phosphatidylcholine-cholesterol-1-O-decylglycerol liposomes were prepared by mechanical dispersion, all with vanillin included. Vesicles were characterized by determination of encapsulation efficiency and vanillin retention capacity. Antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. The hemolytic effect of liposomes was also evaluated by spectrophotometry, as well as the antisickling activity by the Huck test using optical microscopy. Results showed that the lipid composition of liposomes did not significantly affect the encapsulation efficiency. Stable vesicles were obtained with a high retention percentage of vanillin. Liposomes exhibited a high capture of the DPPH radical compared to free vanillin and 1-O-decylglycerol (C10) in solution. Vesicles caused no significant hemolisys in normal erythrocytes, nor in those coming from patients with sickle cell anemia. Vanillin encapsulated in liposomes retained its antisickling activity, with a greater effect for C10-containing vesicles. Our results show that vanillin encapsulation in liposomes is a way to enhance the pharmacologic properties of this molecule using a suitable vehicle.

LHC Experimental Beam Pipe Upgrade during LS1

CERN Document Server

Lanza, G; Baglin, V; Chiggiato, P

2014-01-01

The LHC experimental beam pipes are being improved during the ongoing Long Shutdown 1 (LS1). Several vacuum chambers have been tested and validated before their installation inside the detectors. The validation tests include: leak tightness, ultimate vacuum pressure, material outgassing rate, and residual gas composition. NEG coatings are assessed by sticking probability measurement with the help of Monte Carlo simulations. In this paper the motivation for the beam pipe upgrade, the validation tests of the components and the results are presented and discussed.

Bioactivation mechanism of the cytotoxic and nephrotoxic S-conjugate S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine

International Nuclear Information System (INIS)

Dekant, W.; Lash, L.H.; Anders, M.W.

1987-01-01

The bioactivation of S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC) was studied with purified bovine kidney cysteine conjugate β-lyase and with N-dodecylpyridoxal bromide in cetyltrimethylammonium bromide micelles as a pyridoxal model system. The β-lyase and the pyridoxal model system converted CTFC to chlorofluoroacetic acid and inorganic fluoride, which were identified by 19 F NMR spectrometry. 2-Chloro-1,1,2-trifluoroethanethiol and chlorofluorothionoacetyl fluoride were formed as metabolites of CTFC and were trapped with benzyl bromide and diethylamine, respectively, to yield benzyl 2-chloro-1,1,2-trifluoroethyl sulfide and N,N-diethyl chlorofluorothioacetamide, which were identified by gas chromatography/mass spectrometry. The bioactivation mechanism of CTFC therefore involves the initial formation of the unstable thiol 2-chloro-1,1,2-trifluoroethanethiol, which loses hydrogen fluoride to form the acylating agent chlorofluorothionoacetyl fluoride; hydrolysis of the thionoacyl fluoride affords the stable, terminal metabolites chlorofluoroacetic acid and inorganic fluoride. The intermediate acylating agent and chlorofluoroacetic acid may contribute to the cytotoxic effects of CTFC

EN-CV during LS1: upgrade, consolidation, maintenance, operation

International Nuclear Information System (INIS)

Nonis, M.

2012-01-01

The Cooling and Ventilation (CV) Group in the Engineering Department (EN) will be heavily involved in several projects and activities during the long shutdown in 2013 and 2014 (LS1) within a time-frame limited to around twelve months. According to the requests received so far, most projects are related to the upgrade of users' equipment, consolidation work, and the construction of new plants. However, through the experience gained from the first years of the LHC run, some projects are also needed to adapt the existing installations to the new operating parameters. Some of these projects are presented hereafter, outlining the impact that they will have on operational working conditions or risks of breakdown. Among these projects we find: the PM32 raising pumps, the cooling of the CERN Control Center, R2E, the backup cooling towers for ATLAS and cryogenics, a thermosyphon for ATLAS, or new pumps in UWs. Finally, EN-CV activities during LS1 for maintenance, operation, and commissioning will be mentioned since they represent a major workload for the Group

Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

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Shaoling Wu

2014-02-01

Full Text Available Glial cell line-derived neurotrophic factor (GDNF was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB. In this study, GDNF conventional liposomes (GDNF-L and GDNF target sterically stabilized liposomes (GDNF-SSL-T were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC(0–1 h in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system.

L’AUTOBIOGRAFIA LINGUISTICA NELL’INSEGNAMENTO-APPRENDIMENTO DELL’ITALIANO L2/LS

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Andrea Groppaldi

2010-09-01

Full Text Available L'autobiografia linguistica è una attività particolarmente utile nell'insegnamento-apprendimento di una lingua straniera. L'apprendente immigrato è invitato a narrare in prima persona le esperienze linguistico-comunicative nella propria L1, nella L2 /LS che sta apprendendo e/o nella lingua seconda che ha acquisito come lingua di comunicazione e di studio nel suo paese di origine, le relazioni umane ed emotive che accompagnano  o hanno accompagnato queste esperienze, le situazioni che ne hanno favorito o ostacolato l'apprendimento. Con l'autobiografia linguistica l'apprendente straniero costruisce, attraverso la scrittura e quindi attraverso un processo di esplicitazione e di riflessione consapevole,  un ponte tra "là" e "qui", tra paese d'origine e il paese di arrivo, tra la vita "prima" e la vita "dopo" lo strappo della migrazione. Ricompone e dà senso alla propria storia, nelle due lingue, esprime affetti ed emozioni, rinomina il mondo e se ne riappropria ricostruendo insieme la propria identità, esplora se stesso e si fa conoscere ai suoi pari e all'insegnante in un rapporto di condivisione e di comprensione reciproca: si crea un contesto non di integrazione, ma di inclusione. A sua volta il docente può meglio comprendere le strategie di apprendimento dell'apprendente, la sua personalità, le sue difficoltà e progettare strategie didattiche più efficaci, perché più individuali e orientate al successo nella comunicazione e nell'apprendimento.   Linguistic autobiography is especially useful in the teaching and learning of a foreign language. The foreign learner is asked to narrate, in the first person, his/her linguistic-communicative experiences in their L1 and in the L2/FL which they are learning and/or in the second language they have acquired for communication or study in their home country, focusing on the emotional and human relationships which accompanied this experience and the situations which encouraged or blocked the

Optimization on Preparation Conditions of Salidroside Liposome and Its Immunological Activity on PCV-2 in Mice

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Yibo Feng

2015-01-01

Full Text Available The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2 vaccine adjuvant. Response surface methodology (RSM was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 mol·L−1, ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mL·min−1, and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.

L.S. Vygotsky's Principle "One Step in Learning — A Hundred Steps in Development": In Search of Evidence

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V.K. Zaretsky

2015-10-01

Full Text Available On the basis of L.S. Vygotsky's published works the paper attempts to trace the dynamics of his concepts of child development and to provide evidence supporting Vygotsky's statement that one step in learning equals a hundred in development, which is one of the key principles of culturalhistorical theory in its application to child development. This statement is put in a row with two other major principles: one arguing that learning precedes development and the other referring to the zone of proximal development. The paper outlines a multivector model of the zone of proximal development as one of the conceptual tools of the reflective and activity approach to helping children overcome learning difficulties and promoting their development. The paper also describes a case study in which an orphan child with a disability received psychological and educational support that obviously contributed to the child's development. It is argued that L.S. Vygotsky's idea of the specific relationship between learning and development has fundamental theoretical and practical implications, in particular, for working with children with special needs

Liposome kinetics in infarcted canine myocardium

International Nuclear Information System (INIS)

Caride, V.J.; Twickler, J.; Zaret, B.L.

1984-01-01

To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3 H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02)

Liposome fusion and lipid exchange on ultraviolet irradiation of liposomes containing a photochromic phospholipid

International Nuclear Information System (INIS)

Morgan, C.G.; Sandhu, S.S.; Mitchell, A.C.

1995-01-01

A photochromic phospholipid, 1,2-bis[4-n-butylphenylazo)phenylbutyroyl]phosphatidylcholine (Bis-Azo PC) has been incorporated inot liposomes of gel- and liquid-crystalline-phase phospholipids. Liposomes of gel-phase phospholipid are stable in the presence of the trans photostationary state Bis-Az0 PC and can encapsulate fluorescent marker dye. On photoisomerization to the cis photostationary state, trapped marker is rapidly released. Liposomes containing Bis-Azo PC can rapidly fuse together after UV isomerization, this process continuing in the dark. Exposure to white light causes reversion of Bis-Azo PC to the trans form and halts dye leakage and vesicle fusion. Both unilamellar and multilamellar liposomes are able to fuse together on UV exposure. On UV photolysis, liposomes containing Bis-Azo PC do not fuse with a large excess of unlabeled liposomes, but transfer of Bis-Azo PC can be demonstrated spectrophotometrically. Vesicles of pure gel-phase lipid containing trapped marker dye but initially no Bis-Azo PC become leaky as a result of this lipid transfer. Liposomes composed of liquid-crystalline-phase phosphatidylcholine-containing Bis-Azo PC neither leak trapped marker nor fuse together on photolysis, nor do liquid-crystalline-phase liposomes, fuse with gel-phase liposomes under these conditions. (Author)

Using membrane composition to fine-tune the pKa of an optical liposome pH sensor.

Science.gov (United States)

Clear, Kasey J; Virga, Katelyn; Gray, Lawrence; Smith, Bradley D

2016-04-14

Liposomes containing membrane-anchored pH-sensitive optical probes are valuable sensors for monitoring pH in various biomedical samples. The dynamic range of the sensor is maximized when the probe p K a is close to the expected sample pH. While some biomedical samples are close to neutral pH there are several circumstances where the pH is 1 or 2 units lower. Thus, there is a need to fine-tune the probe p K a in a predictable way. This investigation examined two lipid-conjugated optical probes, each with appended deep-red cyanine dyes containing indoline nitrogen atoms that are protonated in acid. The presence of anionic phospholipids in the liposomes stabilized the protonated probes and increased the probe p K a values by sensor for optimal pH sensing performance.

Optimisation of preparation conditions and properties of phytosterol liposome-encapsulating nattokinase.

Science.gov (United States)

Dong, Xu-Yan; Kong, Fan-Pi; Yuan, Gang-You; Wei, Fang; Jiang, Mu-Lan; Li, Guang-Ming; Wang, Zhan; Zhao, Yuan-Di; Chen, Hong

2012-01-01

Phytosterol liposomes were prepared using the thin film method and used to encapsulate nattokinase (NK). In order to obtain a high encapsulation efficiency within the liposome, an orthogonal experiment (L9 (3)(4)) was applied to optimise the preparation conditions. The molar ratio of lecithin to phytosterols, NK activity and mass ratio of mannite to lecithin were the main factors that influenced the encapsulation efficiency of the liposomes. Based on the results of a single-factor test, these three factors were chosen for this study. We determined the optimum extraction conditions to be as follows: a molar ratio of lecithin to phytosterol of 2 : 1, NK activity of 2500 U mL⁻¹ and a mass ratio of mannite to lecithin of 3 : 1. Under these optimised conditions, an encapsulation efficiency of 65.25% was achieved, which agreed closely with the predicted result. Moreover, the zeta potential, size distribution and microstructure of the liposomes prepared were measured, and we found that the zeta potential was -51 ± 3 mV and the mean diameter was 194.1 nm. From the results of the scanning electron microscopy, we observed that the phytosterol liposomes were round and regular in shape and showed no aggregation.

In situ SAXS experiment during DNA and liposome complexation

Energy Technology Data Exchange (ETDEWEB)

Gasperini, A.A.; Cavalcanti, L.P. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil); Balbino, T.A.; Torre, L.G. de la [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil)

2012-07-01

Full text: Gene therapy is an exciting research area that allows the treatment of different diseases. Basically, an engineered DNA that codes a protein is the therapeutic drug that has to be delivered to the cell nucleus. After that, the DNA transfection process allows the protein production using the cell machinery. However, the efficient delivery needs DNA protection against nucleases and interstitial fluids. In this context, the use of cationic liposome/DNA complexes is a promising strategy for non-viral gene therapy. Liposomes are lipid systems that self-aggregate in bilayers and the use of cationic lipids allows the electrostatic complexation with DNA. In this work, we used SAXS technique to study the complexation kinetics between cationic liposomes and plasmid DNA and evaluate the liposome structural modifications in the presence of DNA. Liposomes were prepared according to [1] using as plasmid DNA vector model a modified version of pVAX1-GFP with luciferase as reporter gene [2]. The complexation was promoted in a SAXS sample holder containing a microchannel to get access to the compartment between two mica windows where the X-ray beam could cross through [3]. We obtained in situ complexation using such sample holder coupled to a fed-batch reactor through a peristaltic pump. The scattering curves were recorded each 30 seconds during the cycles. The DNA was added until a certain final ratio between surface charges previously determined. We studied the form and structure factor model for the liposome bilayer to fit the scattering curves [4]. Structural information such as the bilayer electronic density profiles, number of bilayers and fluidity were determined as a function of the complexation with DNA. These differences can reflect in singular in vitro and in vivo effects. [1] L. G. de la Torre et al. Colloids and Surfaces B: Biointerfaces, 73, 175 (2009) [2] A. R. Azzoni et al. The Journal of Gene Medicine, 9, 392 (2007) [3] L. P. Cavalcanti et al. Review of

Preparation, characterization, and efficient transfection of cationic liposomes and nanomagnetic cationic liposomes

Directory of Open Access Journals (Sweden)

Samadikhah HR

2011-10-01

Full Text Available Hamid Reza Samadikhah1,*, Asia Majidi2,*, Maryam Nikkhah2, Saman Hosseinkhani11Department of Biochemistry, 2Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran *These authors contributed equally to this work Purpose: Cationic liposomes (CLs are composed of phospholipid bilayers. One of the most important applications of these particles is in drug and gene delivery. However, using CLs to deliver therapeutic nucleic acids and drugs to target organs has some problems, including low transfection efficiency in vivo. The aim of this study was to develop novel CLs containing magnetite to overcome the deficiencies. Patients and methods: CLs and magnetic cationic liposomes (MCLs were prepared using the freeze-dried empty liposome method. Luciferase-harboring vectors (pGL3 were transferred into liposomes and the transfection efficiencies were determined by luciferase assay. Firefly luciferase is one of most popular reporter genes often used to measure the efficiency of gene transfer in vivo and in vitro. Different formulations of liposomes have been used for delivery of different kinds of gene reporters. Lipoplex (liposome–plasmid DNA complexes formation was monitored by gel retardation assay. Size and charge of lipoplexes were determined using particle size analysis. Chinese hamster ovary cells were transfected by lipoplexes (liposome-pGL3; transfection efficiency and gene expression level was evaluated by luciferase assay. Results: High transfection efficiency of plasmid by CLs and novel nanomagnetic CLs was achieved. Moreover, lipoplexes showed less cytotoxicity than polyethyleneimine and Lipofectamine™. Conclusion: Novel liposome compositions (1,2-dipalmitoyl-sn-glycero-3-phosphocholine [DPPC]/dioctadecyldimethylammonium bromide [DOAB] and DPPC/cholesterol/DOAB with high transfection efficiency can be useful in gene delivery in vitro. MCLs can also be used for targeted gene delivery, due to

Integration of β-carotene molecules in small liposomes

International Nuclear Information System (INIS)

Andreeva, Atanaska; Popova, Antoaneta

2010-01-01

The most typical feature of carotenoids is the long polyene chain with conjugated double bonds suggesting that they can serve as conductors of electrons, acting as 'molecular wires', important elements in the molecular electronic devices. Carotenoids are essential components of photosynthetic systems, performing different functions as light harvesting, photoprotection and electron transfer. They act also as natural antioxidants. In addition they perform structural role stabilizing the three-dimensional organization of photosynthetic membranes. Carotenoids contribute to the stability of the lipid phase, preserving the membrane integrity under potentially harmful environmental conditions. Carotenoids can be easily integrated into model membranes, facilitating the investigation of their functional roles. In carotenoid-egg phosphatidylcholine (EPC) liposomes ss-carotene is randomly distributed in the hydrocarbon interior of the bilayer, without any preferred, well defined orientation and retains a substantial degree of mobility. Here we investigate the degree of integration of ss-carotene in small unilamellar EPC liposomes and the changes in ss-carotene absorption and Raman spectra due to the lipid-pigment interaction. All observed changes in ss-carotene absorption and Raman spectra may be regarded as a result of the lipid-pigment interactions leading to the polyene geometry distortion and increasing of the environment heterogenety in the liposomes as compared to the solutions.

Phosphatidylserine-Liposomes Promote Tolerogenic Features on Dendritic Cells in Human Type 1 Diabetes by Apoptotic Mimicry

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Silvia Rodriguez-Fernandez

2018-02-01

Full Text Available Type 1 diabetes (T1D is a metabolic disease caused by the autoimmune destruction of insulin-producing β-cells. With its incidence increasing worldwide, to find a safe approach to permanently cease autoimmunity and allow β-cell recovery has become vital. Relying on the inherent ability of apoptotic cells to induce immunological tolerance, we demonstrated that liposomes mimicking apoptotic β-cells arrested autoimmunity to β-cells and prevented experimental T1D through tolerogenic dendritic cell (DC generation. These liposomes contained phosphatidylserine (PS—the main signal of the apoptotic cell membrane—and β-cell autoantigens. To move toward a clinical application, PS-liposomes with optimum size and composition for phagocytosis were loaded with human insulin peptides and tested on DCs from patients with T1D and control age-related subjects. PS accelerated phagocytosis of liposomes with a dynamic typical of apoptotic cell clearance, preserving DCs viability. After PS-liposomes phagocytosis, the expression pattern of molecules involved in efferocytosis, antigen presentation, immunoregulation, and activation in DCs concurred with a tolerogenic functionality, both in patients and control subjects. Furthermore, DCs exposed to PS-liposomes displayed decreased ability to stimulate autologous T cell proliferation. Moreover, transcriptional changes in DCs from patients with T1D after PS-liposomes phagocytosis pointed to an immunoregulatory prolife. Bioinformatics analysis showed 233 differentially expressed genes. Genes involved in antigen presentation were downregulated, whereas genes pertaining to tolerogenic/anti-inflammatory pathways were mostly upregulated. In conclusion, PS-liposomes phagocytosis mimics efferocytosis and leads to phenotypic and functional changes in human DCs, which are accountable for tolerance induction. The herein reported results reinforce the potential of this novel immunotherapy to re-establish immunological

Iron complexation to histone deacetylase inhibitors SAHA and LAQ824 in PEGylated liposomes can considerably improve pharmacokinetics in rats.

Science.gov (United States)

Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May

2014-01-01

The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in

Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody

OpenAIRE

Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L.; Hodge, James W.; Schlom, Jeffrey; Kobayashi, Hisataka

2016-01-01

Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-...

Enhanced bactericidal potency of nanoliposomes by modification of the fusion activity between liposomes and bacterium

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Ma YF

2013-06-01

Full Text Available Yufan Ma,1 Zhao Wang,1,2 Wen Zhao,1 Tingli Lu,1 Rutao Wang,1,2 Qibing Mei,1 Tao Chen1–3 1Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, People's Republic of China; 2Shaanxi Liposome Research Center, Xi'an, Shaanxi, People's Republic of China; 3Xi'an Libang Pharmaceuticals Co, Ltd, Xi'an, People's Republic of China Background: Pseudomonas aeruginosa represents a good model of antibiotic resistance. These organisms have an outer membrane with a low level of permeability to drugs that is often combined with multidrug efflux pumps, enzymatic inactivation of the drug, or alteration of its molecular target. The acute and growing problem of antibiotic resistance of Pseudomonas to conventional antibiotics made it imperative to develop new liposome formulations to overcome these mechanisms, and investigate the fusion between liposome and bacterium. Methods: The rigidity, stability and charge properties of phospholipid vesicles were modified by varying the cholesterol, 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE, and negatively charged lipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol sodium salt (DMPG, 1,2-dimyristoyl-sn-glycero-3-phopho-L-serine sodium salt (DMPS, 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA, nature phosphatidylserine sodium salt from brain and nature phosphatidylinositol sodium salt from soybean concentrations in liposomes. Liposomal fusion with intact bacteria was monitored using a lipid-mixing assay. Results: It was discovered that the fluid liposomes-bacterium fusion is not dependent on liposomal size and lamellarity. A similar degree of fusion was observed for liposomes with a particle size from 100 to 800 nm. The fluidity of liposomes is an essential pre-request for liposomes fusion with bacteria. Fusion was almost completely inhibited by incorporation of cholesterol into fluid liposomes. The increase in the

In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

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Gu MJ

2015-08-01

Full Text Available Meng-Jie Gu,1,* Kun-Feng Li,1,* Lan-Xin Zhang,1 Huan Wang,1 Li-Si Liu,2 Zhuo-Zhao Zheng,2 Nan-Yin Han,1 Zhen-Jun Yang,1 Tian-Yuan Fan1 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 2Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs. Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA, gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. Keywords: magnetic resonance imaging, gadolinium, liposomes, tenascin-C, GBI-10 aptamer, tumor targeting

Gold nanoparticles functionalized with a fragment of the neural cell adhesion molecule L1 stimulate L1-mediated functions

Science.gov (United States)

Schulz, Florian; Lutz, David; Rusche, Norman; Bastús, Neus G.; Stieben, Martin; Höltig, Michael; Grüner, Florian; Weller, Horst; Schachner, Melitta; Vossmeyer, Tobias; Loers, Gabriele

2013-10-01

The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1 sequence of the third fibronectin type III domain of murine L1 was identified and conjugated to gold nanoparticles (AuNPs) to obtain constructs that interact homophilically with the extracellular domain of L1 and trigger the cognate beneficial L1-mediated functions. Covalent conjugation was achieved by reacting mixtures of two cysteine-terminated forms of this L1 peptide and thiolated poly(ethylene) glycol (PEG) ligands (~2.1 kDa) with citrate stabilized AuNPs of two different sizes (~14 and 40 nm in diameter). By varying the ratio of the L1 peptide-PEG mixtures, an optimized layer composition was achieved that resulted in the expected homophilic interaction of the AuNPs. These AuNPs were stable as tested over a time period of 30 days in artificial cerebrospinal fluid and interacted with the extracellular domain of L1 on neurons and Schwann cells, as could be shown by using cells from wild-type and L1-deficient mice. In vitro, the L1-derivatized particles promoted neurite outgrowth and survival of neurons from the central and peripheral nervous system and stimulated Schwann cell process formation and proliferation. These observations raise the hope that, in combination with other therapeutic approaches, L1 peptide-functionalized AuNPs may become a useful tool to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.The neural cell adhesion molecule L1 is involved in nervous system development and promotes regeneration in animal models of acute and chronic injury of the adult nervous system. To translate these conducive functions into therapeutic approaches, a 22-mer peptide that encompasses a minimal and functional L1

LS1 Report: The cryogenic line goes through the scanner

CERN Multimedia

CERN Bulletin

2013-01-01

In spite of the complexity of LS1, with many different activities taking place in parallel and sometimes overlapping, the dashboard shows that work is progressing on schedule. This week, teams have started X-raying the cryogenic line to examine its condition in minute detail.   The LS1 schedule is pretty unfathomable for those who don't work in the tunnels or installations, but if you look down all the columns and stop at the line indicating today’s date, you can see that all of the priority and critical items are bang on time, like a Swiss watch. More specifically: the SMACC project in the LHC is on schedule, with a new testing phase for the interconnections which have already been consolidated; preparations are under way for the cable replacement campaign at Point 1 of the SPS (about 20% of the cables will not be replaced as they are completely unused); and the demineralised water distribution line is back in service, as are the electrical substations for the 400 and 66 kV line...

Exchangeable pulmonary water space evaluation using giant liposomes

International Nuclear Information System (INIS)

Santos, A.C.; Ribeiro, M.J.; Ferreira, N.; De Lima, J.J.P.

1998-01-01

The present work aims to study the potential use of liposomes for the evaluation of pulmonary exchangeable water space, important parameter in some pulmonary oedema situations. This study is based upon the delivery of a diffusible water radiotracer into pulmonary capillary network, which equilibrates with interstitial water space of the lung and returns to the blood circulation. The time constant of this phenomena depends on the magnitude of the water space under study. The release of the diffusible radiotracer in lung capillaries is performed using liposomes with specific formulation. The giant liposomes (15-30μm diameter) used in this study are instable at 37 deg. C. They are biocompatible, biodegradable, with low toxicity and showed no immunogenicity. A water tracer labelled with 99m Tc, encapsulated in the aqueous phase of giant liposomes, has been used. Liposomes were prepared in sterile conditions and with apyrogenic materials. The lipid films composition is L-α-diestearoylphosphatidylcholine (DSPC), L-α-phosphatidyl-DL-glycerol (EPG) and cholesterol (CHOL) (60%/10%/30% mass ratio). After iv injection at +-20 deg. C in the femoral vein of Wistar rats (300g-600g) or albine rabbits (4.5-5Kg), the thermolabile liposomes will be entrapped in lung capillaries and release the radiotracer locally. When the radiodrug is diffusible we will evaluate the volume of the exchangeable pulmonary water analyzing the activity/time curves. These curves are slower for greater water spaces. When the radiotracer is non-diffusible, the disappearance curves are not influenced by the extravascular water space. (author)

Spin Trapping Radicals from Lipid Oxidation in Liposomes in the Presence of Flavonoids

International Nuclear Information System (INIS)

Arshad, N.

2013-01-01

Interactions of four structurally related flavonoids - quercetin, rutin, morin and catechin with peroxyl radicals using liposome/N-tert-butyl-alpha-phenylnitrone (PBN) and liposome -(4-pyridyl-N-oxide)-N-tert-butylnitrone (POBN)-spin trap systems have been studied through spin trapping ESR. Results obtained were different from that of conjugated diene analysis experiments, where lag phases indicated radical scavenging activity of all the flavonoids. No clear lag phase was observed in ESR experiments under same conditions. In the presence of flavonoids decreasing ESR signals of spin adducts in PBN, while no or negligibly smaller spin adducts with POBN system were observed which may be attributed to the possibility that spin traps interacted with free radicals. Experiments with buffer/spin trap systems without liposome revealed that spin adducts were only stable with catechin and destroyed by quercetin, rutin and morin in buffer/spin trap systems. These results further assured that quercetin, rutin and morin not only interacted with peroxyl radicals but also with spin adducts. (author)

Innovative bionanocomposite films of edible proteins containing liposome-encapsulated nisin and halloysite nanoclay.

Science.gov (United States)

Boelter, Juliana Ferreira; Brandelli, Adriano

2016-09-01

Films and coatings based on natural polymers have gained increased interest for food packaging applications. In this work, halloysite and phosphatidylcholine liposomes encapsulating nisin were used to develop nanocomposite films of gelatin and casein. Liposomes prepared with either soybean lecithin or Phospholipon(®) showed particle size ranging from 124 to 178nm and high entrapment efficiency (94-100%). Considering their stability, Phospholipon(®) liposomes with 1.0mg/ml nisin were selected for incorporation into nanocomposite films containing 0.5g/l halloysite. The films presented antimicrobial activity against Listeria monocytogenes, Clostridium perfringens and Bacillus cereus. Scanning electron microscopy revealed that the films had a smooth surface, but showed increased roughness with addition of liposomes and halloysite. Casein films were thinner and slightly yellowish, less rigid and very elastic as compared with gelatin films. Thermogravimetric analysis showed a decrease of the degradation temperature for casein films added with liposomes. The glass transition temperature decreased with addition of liposomes and halloysite. Gelatin and casein films containing nisin-loaded liposomes and halloysite represent an interesting alternative for development of active food packaging. Copyright © 2016 Elsevier B.V. All rights reserved.

A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer.

Science.gov (United States)

Wang, Xiaoyou; Chen, Xianhui; Yang, Xiucong; Gao, Wei; He, Bing; Dai, Wenbing; Zhang, Hua; Wang, Xueqing; Wang, Jiancheng; Zhang, Xuan; Dai, Zhifei; Zhang, Qiang

2016-02-01

Though combination chemotherapy or antitumor nanomedicine is extensively investigated, their combining remains in infancy. Additionally, enhanced delivery of estrogen or its analogs to tumor with highly-expressed estrogen-receptor (ER) is seldom considered, despite its necessity for ER-positive breast cancer treatment. Here, nanomedicine based combination therapy using QLPVM conjugated liposomal tamoxifen (TAM) and doxorubicin (DOX) was designed and testified, where the penta-peptide was derived from Ku70 Bax-binding domain. Quantitative, semi-quantitative and qualitative approaches demonstrated the enhanced endocytosis and cytotoxicity of QLPVM conjugated sterically stabilized liposomes (QLPVM-SSLs) in vitro and in vivo. Mechanism studies of QLPVM excluded the possible electrostatic, hydrophobic or receptor-ligand interactions. However, as a weak cell-penetrating peptide, QLPVM significantly induced drug release from QLPVM-SSLs during their interaction with cells, which was favorable for drug internalization. These findings suggested that the nanomedicine based combination therapy using QLPVM-SSL-TAM and QLPVM-SSL-DOX might provide a rational strategy for Luminal A breast cancer. Breast cancer remains a leading cause of mortality in women worldwide. Although combined therapy using hormonal antagonist and chemotherapy is the norm nowadays, the use of these agents together in a single delivery system has not been tested. Here, the authors investigated this approach using QLPVM conjugated liposomes in in-vitro and in-vivo models. The positive findings may provide a novel direction for breast cancer treatment in the near future. Copyright © 2015 Elsevier Inc. All rights reserved.

Multifunctional quantum dots and liposome complexes in drug delivery.

Science.gov (United States)

Wang, Qi; Chao, Yi-Min

2017-09-03

Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches.

Multifunctional quantum dots and liposome complexes in drug delivery

Science.gov (United States)

Wang, Qi; Chao, Yimin

2018-01-01

Incorporating both diagnostic and therapeutic functions into a single nanoscale system is an effective modern drug delivery strategy. Combining liposomes with semiconductor quantum dots (QDs) has great potential to achieve such dual functions, referred to in this review as a liposomal QD hybrid system (L-QD). Here we review the recent literature dealing with the design and application of L-QD for advances in bio-imaging and drug delivery. After a summary of L-QD synthesis processes and evaluation of their properties, we will focus on their multifunctional applications, ranging from in vitro cell imaging to theranostic drug delivery approaches. PMID:28866655

Cardiovascular and behavioral effects produced by administration of liposome-entrapped GABA into the rat central nervous system.

Science.gov (United States)

Vaz, G C; Bahia, A P C O; de Figueiredo Müller-Ribeiro, F C; Xavier, C H; Patel, K P; Santos, R A S; Moreira, F A; Frézard, F; Fontes, M A P

2015-01-29

Liposomes are nanosystems that allow a sustained release of entrapped substances. Gamma-aminobutyric acid (GABA) is the most prevalent inhibitory neurotransmitter of the central nervous system (CNS). We developed a liposomal formulation of GABA for application in long-term CNS functional studies. Two days after liposome-entrapped GABA was injected intracerebroventricularly (ICV), Wistar rats were submitted to the following evaluations: (1) changes in mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) to ICV injection of bicuculline methiodide (BMI) in anesthetized rats; (2) changes in cardiovascular reactivity to air jet stress in conscious rats; and (3) anxiety-like behavior in conscious rats. GABA and saline-containing pegylated liposomes were prepared with a mean diameter of 200 nm. Rats with implanted cannulas targeted to lateral cerebral ventricle (n = 5-8/group) received either GABA solution (GS), empty liposomes (EL) or GABA-containing liposomes (GL). Following (48 h) central microinjection (2 μL, 0.09 M and 99 g/L) of liposomes, animals were submitted to the different protocols. Animals that received GL demonstrated attenuated response of RSNA to BMI microinjection (GS 48 ± 9, EL 43 ± 9, GL 11 ± 8%; P nervous system. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Octanol-assisted liposome assembly on chip

Science.gov (United States)

Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

2016-01-01

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

IMPARARE L’ITALIANO L2/LS CON TESTI TEATRALI

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Erminia Ardissino

2010-09-01

Full Text Available Il saggio tratta dell'impiego di testi teatrali come fonti di esercizi per l'apprendimento dell'italiano L2/LS. Dopo alcune riflessioni teoriche, si presentano sei proposte di lavoro, con relative soluzioni, adatte a studenti del livello B2-C2 del quadro di riferimento. Si tratta di esercizi ricavati da drammi in un unico atto di Pirandello (La morsa e Lumìe di Sicilia, da Verga (un confronto fra Cavalleria rusticana nella forma drammatica e novellistica, e da Tommaso Landolfi (Ombre. Ogni proposta sfrutta una peculiarità del testo teatrale che si costituisce nell'incontro di dialoghi con didascalie. Anzitutto si tratta di comprendere come si costruiscono i personaggi, quindi di vedere la funzione delle didascalie in relazione al testo, infine di riflettere sulle diverse modalità in cui avvengono i dialoghi, includendo le forme di silenzio. Il testo teatrale appare così molto adatto ad esercizi di lingua, perché mette in gioco le capacità interpretative e immaginative degli studenti, li fa discutere e parlare sulla base delle loro intuizioni.   This paper investigates the use of play scripts as inspiration for Italian L2/FL exercises. After a brief discussion on theory, six project proposals and their solutions, suitable for B2-C2 level students, are presented.  These exercises are based on one-act plays by Pirandello (La Morsa and Lumìe di Sicilia, Verga (a comparison between Cavalleria Rusticana in drama and narrative forms and Tommaso Landolfi (Ombre.  Each project focuses on a specific aspect of the script  and is made up of dialogues with captions. After the way the characters are constructed is investigated, then the function of the captions in relation to the texts is considered, and finally students reflect on the different ways the dialogues are presented, including the pauses. Play scripts lend themselves to language exercises, because they encourage students to use their interpretation skills and imaginations to talk about

Labelled Preformed liposomes with 99MTC-DTPA, 99 MTC-ECD, 99MTC-MDP and 99MTC-MIBI : Labelling procedures and stability studies

International Nuclear Information System (INIS)

Savio, E.O.; Teran, M.A.; Vales, M.E.; Frier, M.

2004-01-01

Liposomes labelled with gamma e miters like 99mTc, can be used for scintigraphic imaging to non-invasively track and quantify the distribution of liposomes in the body. In vitro studies were done to choose a suitable radiopharmaceutical (RF) to be attached to performed liposomes. 99mTc-Complexes (DTPA, ECD, MDP, MIBI) were used to label collagen liposomes. Commercial kits were labelled with 99mTc04-(TechnoNuclear). Quality controls of the RF were performed. Collagen liposomes suspended in saline 0.9% were incubated at 4.25.37 and 60 for 30 min. Efficiency of the labelling procedure was determined by gel filtration using Sephadex G25 (Pharmacia) and NaC10.9%. Samples of 100mL (74MBq), were seeded and fractions of 0.5mL were colleted and measured in an ionisation chamber (Capintec CRC). Stability of the labelled liposomes was assessed incubating 0.5mL, of the suspension with 1mL of human serum during 30 min at 37 . Dialysis was performed using dialysis bags of 64 K pore size and NaCI 0.9% at room temperature. Samples of the saline bath were collected at 30.60 and 90 min. and measured in a solid scintillation counter Ortec.Liposomes labelled with 99mTc-DTPA and 99mTcMIBI showed a labelling efficiency of 80%; liposomes incubated with 99mTc-MDP were labelled in a 50% and 99mTc-ECD did not bind to liposomes in the conditions of study. Incubation of labelled liposomes with human serum showed 50% of strong binding to the plasmatic proteins for 99mTc-DTPA but low values (5%) for the other specimens. Labelled liposomes were achieved, with different RF, showing a suitable in vitro stability to perform in vivo studies

Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

Science.gov (United States)

Kanokpanont, Sorada

The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH pH, PEAR concentration, presence of cholesterol in the liposomes, Ca 2+, and the concentration of sodium alginate. We have also shown possibilities of anchoring PEAR on to liposome by covalent conjugation although this led to inactivation of the polymer. It is also possible to entrap small molecular weight PEAA in liposomes. The evidence of the pH-induced protein release by the interaction of PEAA and liposomes was first demonstrated in this thesis. Kinetic parameters of GO were estimated to use as a basis for determination optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are required to improve the response of the system to the normal blood glucose and to control the total protein

Online size-exclusion high-performance liquid chromatography light scattering and differential refractometry methods to determine degree of polymer conjugation to proteins and protein-protein or protein-ligand association states.

Science.gov (United States)

Kendrick, B S; Kerwin, B A; Chang, B S; Philo, J S

2001-12-15

Characterizing the solution structure of protein-polymer conjugates and protein-ligand interactions is important in fields such as biotechnology and biochemistry. Size-exclusion high-performance liquid chromatography with online classical light scattering (LS), refractive index (RI), and UV detection offers a powerful tool in such characterization. Novel methods are presented utilizing LS, RI, and UV signals to rapidly determine the degree of conjugation and the molecular mass of the protein conjugate. Baseline resolution of the chromatographic peaks is not required; peaks need only be sufficiently separated to represent relatively pure fractions. An improved technique for determining the polypeptide-only mass of protein conjugates is also described. These techniques are applied to determining the degree of erythropoietin glycosylation, the degree of polyethylene glycol conjugation to RNase A and brain-derived neurotrophic factor, and the solution association states of these molecules. Calibration methods for the RI, UV, and LS detectors will also be addressed, as well as online methods to determine protein extinction coefficients and dn/dc values both unconjugated and conjugated protein molecules. (c)2001 Elsevier Science.

The preparation of Tc-99m labeled liposomes by a cationic SP/DOPE formulation for tumor imaging

International Nuclear Information System (INIS)

Yu, M.D.; Hsieh, D.S.; Huang, W.S.

2002-01-01

Aim: Liposomes can provide a gene delivery system to be used in the cancer gene therapy. Radiolabeled liposomes can be used in tumor imaging and tumor therapy. A new cationic liposome formulation of sphingosin e (SP) and dioleoylphosphatidylethanolamine (DOPE) was developed and showed very efficient transfection in a wide variety of mammalian cancer cells, including SKOV-3 (human ovarian carcinoma cells), NPC076 (human nasopharyngeal carcinoma cells), and A431 (human epidermoid carcinoma cells) (Kao et al., Oncol Reports. 5:625-629, 1998). The present study is designed and evaluated the labeling and stability of Tc-99m liposomes by SP/DOPE formulation. Material and Methods: A mixture of 8 mg of SP (Sigma Chemical) and 8 mg of DOPE (Sigma Chemical) dissolved in 4 ml absolute ethanol and used as a lipid stock solution (4 mg/ml). In the direct labeling method, taking 0.25 ml (1 mg) stock solution dried under nitrogen gas and then added 1 ml 20 mM HEPES buffer for hydration 8 hours. The remaining stock solution was dried, hydrated 8 hours, and sonicated 10 min to form liposomes for after-loading labeling method (preformed liposomes). The labeling studies included Tc-99m direct labeling (1), Tc-99m HMPAO direct labeling (2), Tc-99m stannous chloride after-loading labeling (3), Tc-99m HMPAO after-loading labeling (4), and Tc-99m pCMVβ DNA inclusion labeling (5). The labeling efficiency (LE) was determined by thin layer chromatography. The labeled liposomes were incubated with fetal bovine serum (FBS) 30 min to evaluate their stability. Results: It is shown that LE (48%) of Tc-99m direct labeling was the highest in the five methods; however, the LE was reduced to 9% (corrected to original LE) after incubating with serum. Tc-99m may be loosely conjugated to the outer surface of the liposomes. The LE (32%) of Tc-99m HMPAO direct labeling was the second; however, LE was most stable when incubating with serum. The LE of the after-loading labeling was not better than that of

Effect of liposomal formulations and immunostimulating peptidoglycan monomer (PGM) on the immune reaction to ovalbumin in mice.

Science.gov (United States)

Habjanec, Lidija; Frkanec, Ruza; Halassy, Beata; Tomasić, Jelka

2006-01-01

The adjuvant activity of liposomes and immunostimulating peptidoglycan monomer (PGM) in different formulations has been studied in mice model using ovalbumin (OVA) as an antigen. PGM is a natural compound of bacterial origin with well-defined chemical structure: GlcNAc-MurNAc-L-Ala-D-isoGln-mesoDpm(epsilonNH2)-D-Ala-D-Ala. It is a non-toxic, non-pyrogenic, and water-soluble immunostimulator. The aim of this study was to investigate the influence of different liposomal formulations of OVA, with or without PGM, on the production of total IgG, as well as of IgG1 and IgG2a subclasses of OVA-specific antibodies (as indicators of Th2 and Th1 type of immune response, respectively). CBA mice were immunized s.c. with OVA mixed with liposomes, OVA with PGM mixed with liposomes, OVA encapsulated into liposomes and OVA with PGM encapsulated into liposomes. Control groups were OVA in saline, OVA with PGM in saline, and OVA in CFA/IFA adjuvant formulation. The entrapment efficacy of OVA was monitored by HPLC method. The adjuvant activity of the mixture of OVA and empty liposomes, the mixture of OVA, PGM, and liposomes and PGM encapsulated with OVA into liposomes on production of total anti-OVA IgG was demonstrated. The mixture of PGM and liposomes exhibited additive immunostimulating effect on the production of antigen-specific IgGs. The analysis of IgG subclasses revealed that encapsulation of OVA into liposomes favors the stimulation of IgG2a antibodies, indicating the switch toward the Th1 type of immune response. When encapsulated into liposomes or mixed with liposomes, PGM induced a switch from Th1 to Th2 type of immune response. It could be concluded that appropriate formulations of antigen, PGM, and liposomes differently affect the humoral immune response and direct the switch in the type of immune response (Th1/Th2).

RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer

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Feng C

2015-08-01

Full Text Available Chan Feng,1,* Xiaoyan Li,2,* Chunyan Dong,1 Xuemei Zhang,1 Xie Zhang,1 Yong Gao11Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 2Shanghai Tenth People’s Hospital, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: In this study, long-circulating Arg-Gly-Asp (RGD-modified aclacinomycin A (ACM liposomes were prepared by thin film hydration method. Their morphology, particle size, encapsulation efficiency, and in vitro release were investigated. The RGD-ACM liposomes was about 160 nm in size and had the visual appearance of a yellowish suspension. The zeta potential was -22.2 mV and the encapsulation efficiency was more than 93%. The drug-release behavior of the RGD-ACM liposomes showed a biphasic pattern, with an initial burst release and followed by sustained release at a constant rate. After being dissolved in phosphate-buffered saline (pH 7.4 and kept at 4°C for one month, the liposomes did not aggregate and still had the appearance of a milky white colloidal solution. In a pharmacokinetic study, rats treated with RGD-ACM liposomes showed slightly higher plasma concentrations than those treated with ACM liposomes. Maximum plasma concentrations of RGD-ACM liposomes and ACM liposomes were 4,532 and 3,425 ng/mL, respectively. RGD-ACM liposomes had a higher AUC0–∞ (1.54-fold, mean residence time (2.09-fold, and elimination half-life (1.2-fold when compared with ACM liposomes. In an in vivo study in mice, both types of liposomes inhibited growth of human lung adenocarcinoma (A549 cells and markedly decreased tumor size when compared with the control group. There were no obvious pathological tissue changes in any of the treatment groups. Our results indicate that RGD-modified ACM liposomes have a better antitumor effect in vivo than their unmodified counterparts.Keywords: RGD, aclacinomycin A, long-circulating liposomes, pharmacokinetic, tumor

Spread of CTX-M-type ESßLs in isolates of E. coli from long-term care and rehabilitation facilities in Northern Italy

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Elisabetta Nucleo

2008-09-01

Full Text Available During the period March 2003 – May 2004 at the Laboratory of Clinical Microbiology “Redaelli” LTCRF in Milan, Italy, a total of 529 E. coli, obtained from inpatients of 3 different Long Term Care Rehabilitation Facilities (LTCRFs in Northern Italy, were processed and 77 ESßLs producers (14.5% were identified by Vitek System. The results were confirmed by double-disk synergy test with tazobactam (TZP. 61/77 isolates were characterized by higher levels of resistance to cefotaxime (CTX than to ceftazidime (CAZ. (ß-lactamase production was investigated by analytical isoelectric focusing (IEF coupled with a bioassay and showed multiple (ß-lactamase bands including one enzyme with pI 8.4 that, in a bioassay, was more active on CTX,ATM than on CAZ. The presence of (ß-lactamase genes was investigated by colony blot hybridization and by PCR amplification of blaTEM, blaSHV and blaCTX-M alleles. 43/61 isolates produced both TEM-1 and CTX-M-type enzymes, 14/61 expressed only CTX-M-type while in 4 cases were found blaCTX-M, blaTEM and blaSHV genes.The remainders (16/77, characterized by high levels of resistance to both CTX and CAZ, produced TEM-1 and SHV-5 enzymes (1/16 and TEM type ESßLs (15/16. Conjugation experiments, performed in liquid medium, confermed that the ESßLs determinants were transferable. Pulsed-field gel electrophoresis profiles of genomic DNA, digested with NotI, were analysed and revealed clonal heterogeneity. Our work confirms the emergence of CTX-M-type enzymes and their spread in Northern Italy also in longterm care and rehabilitation facilities that may be an important reservoir of ES?L producing E. coli.

The Level of Autoantibodies Targeting Eukaryote Translation Elongation Factor 1 α1 and Ubiquitin-Conjugating Enzyme 2L3 in Nondiabetic Young Adults

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Eunhee G. Kim

2016-01-01

Full Text Available BackgroundThe prevalence of novel type 1 diabetes mellitus (T1DM antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects.MethodsEEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150 and T1DM subjects (n=101 in various ranges of age (18 to 69 years were measured using an enzyme-linked immunosorbent assay. The cutoff point for the presence of each autoantibody was determined based on control subjects using the formula: [mean absorbance+3×standard deviation].ResultsIn nondiabetic subjects, there were no significant correlations between age and EEF1A1-AAb and UBE2L3-AAb levels. However, there was wide variation in EEF1A1-AAb and UBE2L3-AAb levels among control subjects <40 years old; the prevalence of both EEF1A1-AAb and UBE2L3-AAb in these subjects was 4.4%. When using cutoff points determined from the control subjects <40 years old, the prevalence of both autoantibodies in T1DM subjects was decreased (EEFA1-AAb, 15.8% to 8.9%; UBE2L3-AAb, 10.9% to 7.9% when compared to the prevalence using the cutoff derived from the totals for control subjects.ConclusionThere was no association between age and EEF1A1-AAb or UBE2L3-AAb levels in nondiabetic subjects. However, the wide variation in EEF1A1-AAb and UBE2L3-AAb levels apparent among the control subjects <40 years old should be taken into consideration when determining the cutoff reference range for the diagnosis of T1DM.

Pharmacokinetic analysis of 111 in-labeled liposomal Doxorubicin in murine glioblastoma after blood-brain barrier disruption by focused ultrasound.

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Feng-Yi Yang

Full Text Available The goal of this study was to evaluate the pharmacokinetics of targeted and untargeted (111In-doxorubicin liposomes after these have been intravenously administrated to tumor-bearing mice in the presence of blood-brain barrier disruption (BBB-D induced by focused ultrasound (FUS. An intracranial brain tumor model in NOD-scid mice using human brain glioblastoma multiforme (GBM 8401 cells was developed in this study. (111In-labeled human atherosclerotic plaque-specific peptide-1 (AP-1-conjugated liposomes containing doxorubicin (Lipo-Dox; AP-1 Lipo-Dox were used as a microSPECT probe for radioactivity measurements in the GBM-bearing mice. Compared to the control tumors treated with an injection of (111In-AP-1 Lipo-Dox or (111In-Lipo-Dox, the animals receiving the drugs followed by FUS exhibited enhanced accumulation of the drug in the brain tumors (p<0.05. Combining sonication with drugs significantly increased the tumor-to-normal brain doxorubicin ratio of the target tumors compared to the control tumors. The tumor-to-normal brain ratio was highest after the injection of (111In-AP-1 Lipo-Dox with sonication. The (111In-liposomes micro-SPECT/CT should be able to provide important information about the optimum therapeutic window for the chemotherapy of brain tumors using sonication.

The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery

DEFF Research Database (Denmark)

Lund Hansen, Pernille; Blaich, Stephanie; End, Caroline

2011-01-01

Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance...

UFOs in the LHC after LS1

International Nuclear Information System (INIS)

Baer, T.; Barnes, M.J.; Carlier, E.; Cerutti, F.; Dehning, B.; Ducimetiere, L.; Ferrari, A.; Garrel, N.; Gerardin, A.; Goddard, B.; Holzer, E.B.; Jackson, S.; Jimenez, J.M.; Kain, V.; Lechner, A.; Mertens, V.; Misiowiec, M.; Moron Ballester, R.; Nebot del Busto, E.; Norderhaug Drosdal, L.; Nordt, A.; Uythoven, J.; Velghe, B.; Vlachoudis, V.; Wenninger, J.; Zamantzas, C.; Zimmermann, F.; Fuster Martinez, N.

2012-01-01

UFOs (Unidentified Falling Objects) are potentially a major luminosity limitation for nominal LHC operation. With large-scale increases of the BLM thresholds, their impact on LHC availability was mitigated in the second half of 2011. For higher beam energy and lower magnet quench limits, the problem is expected to be considerably worse, though. Therefore, in 2011, the diagnostics for UFO events were significantly improved, dedicated experiments and measurements in the LHC and in the laboratory were made and complemented by FLUKA simulations and theoretical studies. In this paper, the state of knowledge is summarized and extrapolations for LHC operation after LS1 are presented. Mitigation strategies are proposed and related tests and measures for 2012 are specified. (authors)

UFOs in the LHC after LS1

CERN Document Server

Baer, T; Carlier, E; Cerutti, F; Dehning, B; Ducimetière, L; Ferrari, A; Garrel, N; Gérardin, A; Goddard, B; Holzer, E B; Jackson, S; Jimenez, J M; Kain, V; Lechner, A; Mertens, V; Misiowiec, M; Morón Ballester, R; Nebot del Busto, E; Norderhaug Drosdal, L; Nordt, A; Uythoven, J; Velghe, B; Vlachoudis, V; Wenninger, J; Zamantzas, C; Zimmermann, F; Fuster Martinez, N

2012-01-01

UFOs (Unidentified Falling Objects) are potentially a major luminosity limitation for nominal LHC operation. With large-scale increases of the BLM thresholds, their impact on LHC availability was mitigated in the second half of 2011. For higher beam energy and lower magnet quench limits, the problem is expected to be considerably worse, though. Therefore, in 2011, the diagnostics for UFO events were significantly improved, dedicated experiments and measurements in the LHC and in the laboratory were made and complemented by FLUKA simulations and theoretical studies. In this paper, the state of knowledge is summarized and extrapolations for LHC operation after LS1 are presented. Mitigation strategies are proposed and related tests and measures for 2012 are specified.

Preparation and Characterization of Naringenin-Loaded Elastic Liposomes for Topical Application.

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Ming-Jun Tsai

Full Text Available Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic liposomes for naringenin topical application. Naringenin-loaded elastic liposomes containing different amounts of Tween 80 and cholesterol were prepared. The physicochemical properties including vesicle size, surface charge, encapsulation efficiency, and permeability capacity were determined to evaluate the effect of components. The stability of formulation and skin irritation caused by drug-loaded elastic liposomes were also evaluated for assessment of the clinical utility of elastic liposomes. Saturated aqueous solution of naringenin and naringenin dissolved in 10% Tween 80 solution (5 mg/mL were used as the control group. The result showed that in using elastic liposomes as carrier, the deposition amounts in the skin of naringenin were significantly increased about 7.3~11.8-fold and 1.2~1.9-fold respectively, when compared with the saturated aqueous solution and Tween 80 solution-treated groups. The level of drug was more than 98.89±3.90% after 3 months of storage at 4℃. In a skin irritation test, the result showed experimental formulation exhibit considerably less irritating than the positive control (paraformaldehyde-treated group, suggesting its potential therapeutic application.

Neuroprotection against apoptosis of SK-N-MC cells using RMP-7- and lactoferrin-grafted liposomes carrying quercetin

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Kuo Y

2017-04-01

Full Text Available Yung-Chih Kuo, Chien-Wei Tsao Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan, Republic of China Abstract: A drug delivery system of quercetin (QU-encapsulated liposomes (LS grafted with RMP-7, a bradykinin analog, and lactoferrin (Lf was developed to permeate the blood–brain barrier (BBB and rescue degenerated neurons, acting as an Alzheimer’s disease (AD pharmacotherapy. This colloidal formulation of QU-encapsulated LS grafted with RMP-7 and Lf (RMP-7-Lf-QU-LS was used to traverse human brain microvascular endothelial cells (HBMECs regulated by human astrocytes (HAs and to treat SK-N-MC cells after an insult with cytotoxic β-amyloid (Aβ fibrils. We found that surface RMP-7 and Lf enhanced the ability of QU to cross the BBB without inducing strong toxicity and damaging the tight junction. In addition, RMP-7-Lf-QU-LS significantly reduced Aβ-induced neurotoxicity and improved the viability of SK-N-MC cells. Compared with free QU, RMP-7-Lf-QU-LS could also significantly inhibit the expression of phosphorylated c-Jun N terminal kinase, phosphorylated p38, and phosphorylated tau protein at serine 202 by SK-N-MC cells, indicating an important role of RMP-7, Lf, and LS in protecting neurons against apoptosis. RMP-7-Lf-QU-LS is a promising carrier targeting the BBB to prevent Aβ-insulted neurodegeneration and may have potential in managing AD in future clinical applications. Keywords: Alzheimer’s disease, blood–brain barrier, β-amyloid, drug targeting, neurodegeneration, pharmacotherapy

Pharmacokinetics of a 5-fluorouracil liposomal delivery system.

Science.gov (United States)

Simmons, S T; Sherwood, M B; Nichols, D A; Penne, R B; Sery, T; Spaeth, G L

1988-01-01

A liposomal delivery system was developed in an attempt to prolong ocular levels of 5-fluorouracil for glaucoma filtering surgery. The pharmacokinetics of the 5-fluorouracil liposomal delivery system were studied in normal pigmented rabbits with 5-fluorouracil labelled with carbon-14 (C-14). 14C 5-fluorouracil was incorporated into the liposomes at a concentration of 10 g/l and injected subconjunctivally in doses of 5 and 10 mg. Concentrations of 5-fluorouracil were assayed at 10 time intervals from 0.5 to 96 hours in cornea, sclera, and conjunctiva and at six time intervals from 0.5 to 12 hours in aqueous. Two peak concentrations were noted at approximately one and eight hours, with measurable levels present at 96 hours. This study demonstrates the ability of this liposomal delivery system to prolong levels of 5-fluorouracial in normal pigmented rabbits. PMID:3179257

Quenches after LS1

International Nuclear Information System (INIS)

Verweij, A.P.

2012-01-01

In this paper I will give an overview of the different types of quenches that occur in the LHC, followed by an estimate of the number of quenches that we can expect after LS1. Beam-induced quenches and false triggering of the QPS will be the main cause of those quenches that cause a beam dump. Possibly in total up to 10-20 per year. After consolidation of the 13 kA joints, the approach for the BLM settings can be less conservative than in 2010-2012 in order to maximize beam time. This will cause some quenches but, anyhow, a beam.induced quench is not more risky than a quench provoked by false triggering. It is not easy to predict the number of BLM triggered beam dumps, needed to avoid magnet quenches, because it is not sure how to scale beam losses and UFO's from 3.5 TeV to 6.5 TeV, and it is not sure if the thresholds at 3.5 TeV are correct. Quench events will be much more massive (ex: RB quench at 6 kA → 2 MJ, RB quench at 11 kA → 6-20 MJ), and as a result cryo recuperation much longer. There will also be more ramp induced quenches after a FPA in other circuits due to higher ramp rates and smaller temperature margins (mutual coupling)

[Rapid determination of COD in aquaculture water based on LS-SVM with ultraviolet/visible spectroscopy].

Science.gov (United States)

Liu, Xue-Mei; Zhang, Hai-Liang

2014-10-01

Ultraviolet/visible (UV/Vis) spectroscopy was studied for the rapid determination of chemical oxygen demand (COD), which was an indicator to measure the concentration of organic matter in aquaculture water. In order to reduce the influence of the absolute noises of the spectra, the extracted 135 absorbance spectra were preprocessed by Savitzky-Golay smoothing (SG), EMD, and wavelet transform (WT) methods. The preprocessed spectra were then used to select latent variables (LVs) by partial least squares (PLS) methods. Partial least squares (PLS) was used to build models with the full spectra, and back- propagation neural network (BPNN) and least square support vector machine (LS-SVM) were applied to build models with the selected LVs. The overall results showed that BPNN and LS-SVM models performed better than PLS models, and the LS-SVM models with LVs based on WT preprocessed spectra obtained the best results with the determination coefficient (r2) and RMSE being 0. 83 and 14. 78 mg · L(-1) for calibration set, and 0.82 and 14.82 mg · L(-1) for the prediction set respectively. The method showed the best performance in LS-SVM model. The results indicated that it was feasible to use UV/Vis with LVs which were obtained by PLS method, combined with LS-SVM calibration could be applied to the rapid and accurate determination of COD in aquaculture water. Moreover, this study laid the foundation for further implementation of online analysis of aquaculture water and rapid determination of other water quality parameters.

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

Science.gov (United States)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

2011-06-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M-1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t 1/2 of 21.4 min and β- t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Efficient CUDA Polynomial Preconditioned Conjugate Gradient Solver for Finite Element Computation of Elasticity Problems

Directory of Open Access Journals (Sweden)

Jianfei Zhang

2013-01-01

Full Text Available Graphics processing unit (GPU has obtained great success in scientific computations for its tremendous computational horsepower and very high memory bandwidth. This paper discusses the efficient way to implement polynomial preconditioned conjugate gradient solver for the finite element computation of elasticity on NVIDIA GPUs using compute unified device architecture (CUDA. Sliced block ELLPACK (SBELL format is introduced to store sparse matrix arising from finite element discretization of elasticity with fewer padding zeros than traditional ELLPACK-based formats. Polynomial preconditioning methods have been investigated both in convergence and running time. From the overall performance, the least-squares (L-S polynomial method is chosen as a preconditioner in PCG solver to finite element equations derived from elasticity for its best results on different example meshes. In the PCG solver, mixed precision algorithm is used not only to reduce the overall computational, storage requirements and bandwidth but to make full use of the capacity of the GPU devices. With SBELL format and mixed precision algorithm, the GPU-based L-S preconditioned CG can get a speedup of about 7–9 to CPU-implementation.

LS1 Report: Summer cool down

CERN Multimedia

Katarina Anthony

2014-01-01

As the final LS1 activities are carried out in the machine, teams have been cooling down the accelerator sector by sector in preparation for beams.   The third sector of the LHC to be cooled down - sector 1-2 - has seen the process begin this week. During the cool-down phase, survey teams are measuring and smoothing (or realigning) the magnets at cold. By the end of August, five sectors of the machine will be in the process of cooling down, with one (sector 6-7) at cold. The LHC Access Safety System (LASS) is now being commissioned, and will be validated during the DSO tests at the beginning of October. As teams consolidate the modifications made to LASS during the shutdown, many points were closed for testing purposes. The CSCM (copper stabiliser continuity measurement) tests have been completed in the first sector (6-7) and no defect has been found. These results will be presented to the LHC Machine Committee next week. CSCM tests will start in the second sector in mid-August. Following many...

Kynurenine aminotransferase III and glutamine transaminase L are identical enzymes that have cysteine S-conjugate β-lyase activity and can transaminate L-selenomethionine.

Science.gov (United States)

Pinto, John T; Krasnikov, Boris F; Alcutt, Steven; Jones, Melanie E; Dorai, Thambi; Villar, Maria T; Artigues, Antonio; Li, Jianyong; Cooper, Arthur J L

2014-11-07

Three of the four kynurenine aminotransferases (KAT I, II, and IV) that synthesize kynurenic acid, a neuromodulator, are identical to glutamine transaminase K (GTK), α-aminoadipate aminotransferase, and mitochondrial aspartate aminotransferase, respectively. GTK/KAT I and aspartate aminotransferase/KAT IV possess cysteine S-conjugate β-lyase activity. The gene for the former enzyme, GTK/KAT I, is listed in mammalian genome data banks as CCBL1 (cysteine conjugate beta-lyase 1). Also listed, despite the fact that no β-lyase activity has been assigned to the encoded protein in the genome data bank, is a CCBL2 (synonym KAT III). We show that human KAT III/CCBL2 possesses cysteine S-conjugate β-lyase activity, as does mouse KAT II. Thus, depending on the nature of the substrate, all four KATs possess cysteine S-conjugate β-lyase activity. These present studies show that KAT III and glutamine transaminase L are identical enzymes. This report also shows that KAT I, II, and III differ in their ability to transaminate methyl-L-selenocysteine (MSC) and L-selenomethionine (SM) to β-methylselenopyruvate (MSP) and α-ketomethylselenobutyrate, respectively. Previous studies have identified these seleno-α-keto acids as potent histone deacetylase inhibitors. Methylselenol (CH3SeH), also purported to have chemopreventive properties, is the γ-elimination product of SM and the β-elimination product of MSC catalyzed by cystathionine γ-lyase (γ-cystathionase). KAT I, II, and III, in part, can catalyze β-elimination reactions with MSC generating CH3SeH. Thus, the anticancer efficacy of MSC and SM will depend, in part, on the endogenous expression of various KAT enzymes and cystathionine γ-lyase present in target tissue coupled with the ability of cells to synthesize in situ either CH3SeH and/or seleno-keto acid metabolites. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Conjugated polymer zwitterions and solar cells comprising conjugated polymer zwitterions

Science.gov (United States)

Emrick, Todd; Russell, Thomas; Page, Zachariah; Liu, Yao

2018-06-05

A conjugated polymer zwitterion includes repeating units having structure (I), (II), or a combination thereof ##STR00001## wherein Ar is independently at each occurrence a divalent substituted or unsubstituted C3-30 arylene or heteroarylene group; L is independently at each occurrence a divalent C1-16 alkylene group, C6-30arylene or heteroarylene group, or alkylene oxide group; and R1 is independently at each occurrence a zwitterion. A polymer solar cell including the conjugated polymer zwitterion is also disclosed.

Entrapment of ovalbumin into liposomes--factors affecting entrapment efficiency, liposome size, and zeta potential.

Science.gov (United States)

Brgles, Marija; Jurasin, Darija; Sikirić, Maja Dutour; Frkanec, Ruza; Tomasić, Jelka

2008-01-01

Various amounts of Ovalbumin (OVA) were encapsulated into positively and negatively charged multilamellar liposomes, with the aim to investigate the entrapment efficiency in different buffers and to study their effects on the liposome size and zeta potential. Results showed that the entrapment efficiency of OVA in anionic liposomes was the same in 10 mM Phosphate Buffer (PB) as in Phosphate-Buffered Saline (PBS; PB + 0.15 M NaCl). Also, liposome size was approximately 1200 nm for all anionic liposomes incorporating OVA. The entrapment efficiency of OVA in cationic liposomes was highly dependent on ionic strength. The size of cationic liposomes was approximately 1200 nm in PBS, regardless of protein content, but increased with the amount of the incorporated protein in PB. Aggregation of cationic liposomes in PB was observed when the mass of the protein was 2.5 mg or greater. The zeta potential of anionic liposomes was negative and of cationic liposomes positive in the whole range of protein mass tested. These results show how different compositions of lipid and aqueous phases can be used to vary the entrapment efficiency, liposome size, and zeta potential--the factors that are of great importance for the use of liposomes as drug carriers.

Dynamic Morphological Changes Induced By GM1 and Protein Interactions on the Surface of Cell-Sized Liposomes

Directory of Open Access Journals (Sweden)

Masahiro Takagi

2013-06-01

Full Text Available It is important to understand the physicochemical mechanisms that are responsible for the morphological changes in the cell membrane in the presence of various stimuli such as osmotic pressure. Lipid rafts are believed to play a crucial role in various cellular processes. It is well established that Ctb (Cholera toxin B subunit recognizes and binds to GM1 (monosialotetrahexosylganglioside on the cell surface with high specificity and affinity. Taking advantage of Ctb-GM1 interaction, we examined how Ctb and GM1 molecules affect the dynamic movement of liposomes. GM1 a natural ligand for cholera toxin, was incorporated into liposome and the interaction between fluorescent Ctb and the liposome was analyzed. The interaction plays an important role in determining the various surface interaction phenomena. Incorporation of GM1 into membrane leads to an increase of the line tension leading to either rupture of liposome membrane or change in the morphology of the membrane. This change in morphology was found to be GM1 concentration specific. The interaction between Ctb-GM1 leads to fast and easy rupture or to morphological changes of the liposome. The interactions of Ctb and the glycosyl chain are believed to affect the surface and the curvature of the membrane. Thus, the results are highly beneficial in the study of signal transduction processes.

Liposome-encapsulated chemotherapy

DEFF Research Database (Denmark)

Børresen, B.; Hansen, A. E.; Kjær, A.

2018-01-01

Cytotoxic drugs encapsulated into liposomes were originally designed to increase the anticancer response, while minimizing off-target adverse effects. The first liposomal chemotherapeutic drug was approved for use in humans more than 20years ago, and the first publication regarding its use...... to inherent issues with the enhanced permeability and retention effect, the tumour phenomenon which liposomal drugs exploit. This effect seems very heterogeneously distributed in the tumour. Also, it is potentially not as ubiquitously occurring as once thought, and it may prove important to select patients...... not resolve the other challenges that liposomal chemotherapy faces, and more work still needs to be done to determine which veterinary patients may benefit the most from liposomal chemotherapy....

Undulating tubular liposomes through incorporation of a synthetic skin ceramide into phospholipid bilayers.

Science.gov (United States)

Xu, Peng; Tan, Grace; Zhou, Jia; He, Jibao; Lawson, Louise B; McPherson, Gary L; John, Vijay T

2009-09-15

Nonspherical liposomes were prepared by doping L-alpha-phosphatidylcholine (PC) with ceramide VI (a skin lipid). Cryo-transmission electron microscopy shows the liposome shape changing from spherical to an undulating tubular morphology, when the amount of ceramide VI is increased. The formation of tubular liposomes is energetically favorable and is attributed to the association of ceramide VI with PC creating regions of lower curvature. Since ceramides are the major component of skin lipids in the stratum corneum, tubular liposomes containing ceramide may potentially serve as self-enhanced nanocarriers for transdermal delivery.

Co-encapsulation of chrysophsin-1 and epirubicin in PEGylated liposomes circumvents multidrug resistance in HeLa cells.

Science.gov (United States)

Lo, Yu-Li; Tu, Wei-Chen

2015-12-05

Chrysophsin-1, an amphipathic alpha-helical antimicrobial peptide, is isolated from the gills of the red sea bream and possesses different structure and mechanism(s) in comparison with traditional multidrug resistance (MDR) modulators. For the purpose of reducing off-target normal cell toxicity, it is rational to incorporate chrysophsin-1 and epirubicin in a PEGylated liposomal formulation. In the present study, we report a multifunctional liposomes with epirubicin as an antineoplastic agent and an apoptosis inducer, as well as chrysophsin-1 as a MDR transporter inhibitor and an apoptosis modulator in human cervical cancer HeLa cells. Co-incubation of HeLa cells with PEGylated liposomal formulation of epirubicin and chrysophsin-1 resulted in a significant increase in the cytotoxicity of epirubicin. The liposomal formulations of epirubicin and/or chrysophsin-1 were shown to considerably improve the intracellular H2O2 and O2(-) levels of HeLa cells. Furthermore, these treatments were found to extensively reduce mRNA expression levels of MDR1, MRP1, and MRP2. The addition of chrysophsin-1 in liposomes was demonstrated to substantially enhance the intracellular accumulation of epirubicin in HeLa cells. Moreover, the PEGylated liposomes of epirubicin and chrysophsin-1 were also found to significantly increase the mRNA expressions of p53, Bax, and Bcl-2. The ratio of Bax to Bcl-2 was noticeably amplified in the presence of these formulations. Apoptosis induction was also validated by chromatin condensation, a reduction in mitochondrial membrane potential, the increased sub-G1 phase of cell cycle, and more populations of apoptosis using annexin V/PI assay. These formulations were verified to increase the activity and mRNA expression levels of caspase-9 and caspases-3. Collectively, our findings provide the first evidence that cotreatment with free or liposomal chrysophsin-1 and epirubicin leads to cell death in human cervical cancer cells through the ROS

Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

Energy Technology Data Exchange (ETDEWEB)

Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

2011-06-15

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

Energy Technology Data Exchange (ETDEWEB)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D. [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B. [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V., E-mail: vawasthi@ouhsc.edu [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

2011-06-15

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Cytotoxicity of S-conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (Compound A) in a human proximal tubular cell line

International Nuclear Information System (INIS)

Altuntas, T. Gul; Zager, Richard A.; Kharasch, Evan D.

2003-01-01

Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) is a fluorinated alkene formed by degradation of the volatile anesthetic sevoflurane in anesthesia machines. FDVE is nephrotoxic in rats but not humans. Rat FDVE nephrotoxicity is attributed to FDVE glutathione conjugation and bioactivation of subsequent FDVE-cysteine S-conjugates, in part by renal β-lyase. Although FDVE conjugation and metabolism occur in both rats and humans, the mechanism for selective toxicity in rats and lack of effect in humans is incompletely elucidated. This investigation measured FDVE S-conjugate cytotoxicity in cultured human proximal tubular HK-2 cells, and compared this with known cytotoxic S-conjugates. HK-2 cells were incubated with FDVE and its GSH, cysteine S-mercapturic acid, cysteine S-sulfoxide, and mercapturic acid sulfoxide conjugates (0.1-2.7 mM) for 24 h. Cytotoxicity was determined by lactate dehydrogenase (LDH) release, total LDH, and the ability of viable cells to reduce a tetrazolium-based compound (MTT). FDVE was cytotoxic only at concentrations ≥0.9 mM. No increase in LDH release was observed with either FDVE-GSH conjugate. The FDVE-cysteine conjugates S-(1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl) ethyl)-L-cysteine (DFEC) and (Z)-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-L-cysteine ((Z)-FFVC) caused significant differences in LDH release and MTT reduction only at 2.7 mM; (Z)-FFVC was slightly more cytotoxic. Both S-(1,1-difluoro-2-fluoromethoxy-2-(trifluoromethyl) ethyl)-L-cysteine sulfoxide (DFEC-SO) and (Z)-N-acetyl-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-L-cysteine sulfoxide ((Z)-N-Ac-FFVC-SO) caused slightly greater changes in LDH release or total LDH than the corresponding equimolar DFEC and (Z)-N-acetyl-S-(1-fluoro-2-fluoromethoxy-2-(trifluoromethyl) vinyl)-L-cysteine ((Z)-N-Ac-FFVC) conjugates. In contrast to FDVE S-conjugates, S-(1,2-dichlorovinyl)-L-cysteine was markedly cytotoxic, at concentrations as low as 0.1

Intracellular targeting of mercaptoundecahydrododecaborate (BSH) to malignant glioma by transferrin-PEG liposomes for boron neutron capture therapy (BNCT)

International Nuclear Information System (INIS)

Doi, Atsushi; Miyatake, Shin-ichi; Iida, Kyouko

2006-01-01

Malignant glioma is one of the most difficult tumor to control with usual therapies. In our institute, we select boron neutron capture therapy (BNCT) as an adjuvant radiation therapy after surgical resection. This therapy requires the selective delivery of high concentration of 10 B to malignant tumor tissue. In this study, we focused on a tumor-targeting 10 B delivery system (BDS) for BNCT that uses transferrin-conjugated polyethylene-glycol liposome encapsulating BSH (TF-PEG liposome-BSH) and compared 10 B uptake of the tumor among BSH, PEG liposome-BSH and TF-PEG liposome-BSH. In vitro, we analyzed 10 B concentration of the cultured human U87Δ glioma cells incubated in medium containing 20 μg 10 B/ml derived from each BDS by inductively coupled plasma atomic emission spectrometry (ICP-AES). In vivo, human U87Δ glioma-bearing nude mice were administered with each BDS (35mg 10 B/kg) intravenously. We analyzed 10 B concentration of tumor, normal brain and blood by ICP-AES. The TF-PEG liposome-BSH showed higher absolute concentration more than the other BDS. Moreover, TF-PEG liposome-BSH decreased 10 B concentration in blood and normal tissue while it maintained high 10 B concentration in tumor tissue for a couple of days. This showed the TF-PEG liposome-BSH caused the selective delivery of high concentration of 10 B to malignant tumor tissue. The TF-PEG liposome-BSH is more potent BDS for BNCT to obtain absolute high 10 B concentration and good contrast between tumor and normal tissue than BSH and PEG liposome-BSH. (author)

Calcium-Responsive Liposomes via a Synthetic Lipid Switch.

Science.gov (United States)

Lou, Jinchao; Carr, Adam J; Watson, Alexa J; Mattern-Schain, Samuel I; Best, Michael D

2018-03-07

Liposomal drug delivery would benefit from enhanced control over content release. Here, we report a novel avenue for triggering release driven by chemical composition using liposomes sensitized to calcium-a target chosen due to its key roles in biology and disease. To demonstrate this principle, we synthesized calcium-responsive lipid switch 1, designed to undergo conformational changes upon calcium binding. The conformational change perturbs membrane integrity, thereby promoting cargo release. This was shown through fluorescence-based release assays via dose-dependent response depending on the percentage of 1 in liposomes, with minimal background leakage in controls. DLS experiments indicated dramatic changes in particle size upon treatment of liposomes containing 1 with calcium. In a comparison of ten naturally occurring metal cations, calcium provided the greatest release. Finally, STEM images showed significant changes in liposome morphology upon treatment of liposomes containing 1 with calcium. These results showcase lipid switches driven by molecular recognition principles as an exciting avenue for controlling membrane properties. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

LS1 “First Long Shutdown of LHC and its Injector Chains”

CERN Multimedia

Foraz, K; Barberan, M; Bernardini, M; Coupard, J; Gilbert, N; Hay, D; Mataguez, S; McFarlane, D

2014-01-01

The LHC and its Injectors were stopped in February 2013, in order to maintain, consolidate and upgrade the different equipment of the accelerator chain, with the goal of achieving LHC operation at the design energy of 14 TeV in the centre-of-mass. Prior to the start of this First Long Shutdown (LS1), a major effort of preparation was performed in order to optimize the schedule and the use of resources across the different machines, with the aim of resuming LHC physics in early 2015. The rest of the CERN complex will restart beam operation in the second half of 2014. This paper presents the schedule of the LS1, describes the organizational set-up for the coordination of the works, the main activities, the different main milestones, which have been achieved so far, and the decisions taken in order to mitigate the issues encountered.

LS1 to LHC Report: LHC key handed back to Operations

CERN Multimedia

CERN Bulletin

2015-01-01

This week, after 23 months of hard work involving about 1000 people every day, the key to the LHC was symbolically handed back to the Operations team. The first long shutdown is over and the machine is getting ready for a restart that will bring its beam to full energy in early spring.   Katy Foraz, LS1 activities coordinator, symbolically hands the LHC key to the operations team, represented, left to right, by Jorg Wenninger, Mike Lamont and Mirko Pojer. All the departments, all the machines and all the experimental areas were involved in the first long shutdown of the LHC that began in February 2013. Over the last two years, the Bulletin has closely followed  all the work and achievements that had been carefully included in the complex general schedule drawn up and managed by the team led by Katy Foraz from the Engineering Department. “The work on the schedule began two years before the start of LS1 and one of the first things we realised was that there was no commercial...

Preparation and ocular pharmacokinetics of ganciclovir liposomes.

Science.gov (United States)

Shen, Yan; Tu, Jiasheng

2007-12-07

Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor concentration-time profiles of both liposomes and solution were well described by 2-compartmental pharmacokinetics with first-order absorption. The area under the curve of the aqueous humor concentration-time profiles of GCV liposomes was found to be 1.7-fold higher than that of GCV solution. Ocular tissue distribution of GCV from liposomes was 2 to 10 times higher in the sclera, cornea, iris, lens, and vitreous humor when compared with those observed after solution dosing. These results suggested that liposomes may hold some promise in ocular GCV delivery.

Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

KAUST Repository

Kieler-Ferguson, Heidi M.

2013-01-17

For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

A new Em-like protein from Lactuca sativa, LsEm1, enhances drought and salt stress tolerance in Escherichia coli and rice.

Science.gov (United States)

Xiang, Dian-Jun; Man, Li-Li; Zhang, Chun-Lan; Peng-Liu; Li, Zhi-Gang; Zheng, Gen-Chang

2018-02-07

Late embryogenesis abundant (LEA) proteins are closely related to abiotic stress tolerance of plants. In the present study, we identified a novel Em-like gene from lettuce, termed LsEm1, which could be classified into group 1 LEA proteins, and shared high homology with Cynara cardunculus Em protein. The LsEm1 protein contained three different 20-mer conserved elements (C-element, N-element, and M-element) in the C-termini, N-termini, and middle-region, respectively. The LsEm1 mRNAs were accumulated in all examined tissues during the flowering and mature stages, with a little accumulation in the roots and leaves during the seedling stage. Furthermore, the LsEm1 gene was also expressed in response to salt, dehydration, abscisic acid (ABA), and cold stresses in young seedlings. The LsEm1 protein could effectively reduce damage to the lactate dehydrogenase (LDH) and protect LDH activity under desiccation and salt treatments. The Escherichia coli cells overexpressing the LsEm1 gene showed a growth advantage over the control under drought and salt stresses. Moreover, LsEm1-overexpressing rice seeds were relatively sensitive to exogenously applied ABA, suggesting that the LsEm1 gene might depend on an ABA signaling pathway in response to environmental stresses. The transgenic rice plants overexpressing the LsEm1 gene showed higher tolerance to drought and salt stresses than did wild-type (WT) plants on the basis of the germination performances, higher survival rates, higher chlorophyll content, more accumulation of soluble sugar, lower relative electrolyte leakage, and higher superoxide dismutase activity under stress conditions. The LsEm1-overexpressing rice lines also showed less yield loss compared with WT rice under stress conditions. Furthermore, the LsEm1 gene had a positive effect on the expression of the OsCDPK9, OsCDPK13, OsCDPK15, OsCDPK25, and rab21 (rab16a) genes in transgenic rice under drought and salt stress conditions, implying that overexpression of these

Pharmacokinetics and efficacy of PEGylated liposomal doxorubicin in an intracranial model of breast cancer.

Directory of Open Access Journals (Sweden)

Carey K Anders

Full Text Available Breast cancer brain metastases (BCBM are a challenging consequence of advanced BC. Nanoparticle agents, including liposomes, have shown enhanced delivery to solid tumors and brain. We compared pharmacokinetics (PK and efficacy of PEGylated liposomal doxorubicin (PLD with non-liposomal doxorubicin (NonL-doxo in an intracranial model of BC.Athymic mice were inoculated intracerebrally with MDA-MB-231-BR-luciferase-expressing cells. Tumor-bearing mice were administered PLD or NonL-doxo at 6 mg/kg IV × 1 and were euthanized prior to and 0.083, 1, 3, 6, 24, 72 and 96 h post-treatment. Samples were processed to measure sum total doxorubicin via HPLC. PLD and NonL-doxo were administered IV weekly as single agents (6 mg/kg or in combination (4.5 mg/kg with the PARP inhibitor, ABT-888, PO 25 mg/kg/day. Efficacy was assessed by survival and bioluminescence.Treatment with PLD resulted in approximately 1,500-fold higher plasma and 20-fold higher intracranial tumor sum total doxorubicin AUC compared with NonL-doxo. PLD was detected at 96 h; NonL-doxo was undetectable after 24 h in plasma and tumor. Median survival of PLD-treated animals was 32 days (d, [CI] 31-38, which was significantly longer than controls (26d [CI 25-28]; p = 0.0012 or NonL-doxo treatment (23.5d [CI 18-28], p = 0.0002. Combination treatment with PLD/ABT-888 yielded improved survival compared to NonL-doxo/ABT-888 (35d [CI 31-38] versus 29.5d [CI 25-34]; p = 0.006.PLD provides both PK and efficacy advantage over NonL-doxo in the treatment of an in vivo model of BCBM. The results provide preclinical rationale to translate findings into early phase trials of PLD, with or without ABT-888, for patients with BCBM.

Liposomal curcumin and its application in cancer

Directory of Open Access Journals (Sweden)

Feng T

2017-08-01

Full Text Available Ting Feng,1,* Yumeng Wei,1,* Robert J Lee,2 Ling Zhao1 1Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA *These authors contributed equally to this work Abstract: Curcumin (CUR is a yellow polyphenolic compound derived from the plant turmeric. It is widely used to treat many types of diseases, including cancers such as those of lung, cervices, prostate, breast, bone and liver. However, its effectiveness has been limited due to poor aqueous solubility, low bioavailability and rapid metabolism and systemic elimination. To solve these problems, researchers have tried to explore novel drug delivery systems such as liposomes, solid dispersion, microemulsion, micelles, nanogels and dendrimers. Among these, liposomes have been the most extensively studied. Liposomal CUR formulation has greater growth inhibitory and pro-apoptotic effects on cancer cells. This review mainly focuses on the preparation of liposomes containing CUR and its use in cancer therapy. Keywords: curcumin, liposomes, drug delivery, bioavailability, cancer 

Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

Science.gov (United States)

Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

2017-11-15

A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

Directory of Open Access Journals (Sweden)

Gehrmann MK

2015-09-01

Full Text Available Mathias K Gehrmann,1 Melanie A Kimm,2 Stefan Stangl,1 Thomas E Schmid,1 Peter B Noël,2 Ernst J Rummeny,2 Gabriele Multhoff11Department of Radiation Oncology, 2Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technische Universität München, Munich, GermanyAbstract: Real-time imaging of small tumors is still one of the challenges in cancer diagnosis, prognosis, and monitoring of clinical outcome. Targeting novel biomarkers that are selectively expressed on a large variety of different tumors but not normal cells has the potential to improve the imaging capacity of existing methods such as computed tomography. Herein, we present a novel technique using cmHsp70.1 monoclonal antibody-conjugated spherical gold nanoparticles for quantification of the targeted uptake of gold nanoparticles into membrane Hsp70-positive tumor cells. Upon binding, cmHsp70.1-conjugated gold nanoparticles but not nanoparticles coupled to an isotype-matched IgG1 antibody or empty nanoparticles are rapidly taken up by highly malignant Hsp70 membrane-positive mouse tumor cells. After 24 hours, the cmHsp70.1-conjugated gold nanoparticles are found to be enriched in the perinuclear region. Specificity for membrane Hsp70 was shown by using an Hsp70 knockout tumor cell system. Toxic side effects of the cmHsp70.1-conjugated nanoparticles are not observed at a concentration of 1–10 µg/mL. Experiments are ongoing to evaluate whether cmHsp70.1 antibody-conjugated gold nanoparticles are suitable for the detection of membrane-Hsp70-positive tumors in vivo.Keywords: heat shock protein 70, tumor biomarker, theranostics, multimodal CT, multispectral CT, k-edge

LS1 Report: achieving the unachievable

CERN Multimedia

Anaïs Schaeffer

2013-01-01

The dismantling and extraction of a defective DFBA module from LHC Point 6, announced a few weeks ago, has been completed without a hitch. The DFBAs in the LHC are unique and irreplaceable components that must be handled with care.   The Transport team extract the defective module in one of the two DFBAs at Point 6. This module was brought to the surface, where it is currently being repared. Dismantling and extracting part of an electrical feed box (DFBA) had not been planned and could not have been foreseen. Nonetheless, that is what had to be done. When the LS1 teams discovered that the bellows of one of the DFBAs in Sector 5-6 were damaged - and completely inaccessible - they were not exactly overwhelmed with solutions. In fact, they had only one option: to dismantle them and take them up to the surface. Step 1: measure the alignment of the module to be taken out in relation to the beam lines to ensure that when the DFBA is put back in, it is in the right position for the beam to pass thr...

Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

International Nuclear Information System (INIS)

Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

2011-01-01

3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M −1 . The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t 1/2 of 21.4 min and β-t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

Conjugal transfer of plasmid pAM beta 1 in Lactobacillus reuteri and between lactobacilli and Enterococcus faecalis.

OpenAIRE

Tannock, G W

1987-01-01

The broad-host-range plasmid pAM beta 1 (erythromycin resistance) was transferred conjugally from Streptococcus lactis to Lactobacillus reuteri, L. murinus, and L. fermentum. Transfer of pAM beta 1 between two L. reuteri strains occurred, and lactobacillus transconjugants could act as donors of pAM beta 1 in crosses with Enterococcus faecalis JH2-2.

The successful completion of LS1, consolidation and preparations for the future

CERN Multimedia

Antonella Del Rosso

2014-01-01

For CERN’s Technology (TE) Department, success in LS1 is more important than finishing. In other words, the aim is to reach the finish line having maintained the highest standards of safety, quality and performance. Other challenges need to be faced too, before, during and after LS1, and the Department always approaches them with optimism. The new Department Head tells us how his 750 colleagues work to keep the Laboratory at the cutting edge of high-energy physics technology.   José Miguel Jiménez. “We can only grow once we’ve stabilised our base.” The message presented by José Miguel Jiménez, who stepped into the role of TE Department Head in January 2014, is clear, as are his priorities going forward: “The Technology Department needs to be consolidated in terms of both its personnel and its assembly and test infrastructures, some of which are unique.” The TE Department is tasked with pr...

Ultrasound-mediated drug delivery using liposomes modified with a thermosensitive polymer.

Science.gov (United States)

Ninomiya, Kazuaki; Kawabata, Shinya; Tashita, Hiroyuki; Shimizu, Nobuaki

2014-01-01

Ultrasound-mediated drug delivery was established using liposomes that were modified with the thermosensitive polymer (TSP) poly(NIPMAM-co-NIPAM), which sensitized the liposomes to high temperatures. TSP-modified liposomes (TSP liposomes) released encapsulated calcein under 1 MHz ultrasound irradiation at 0.5 W/cm(2) for 120 s as well as the case under incubation at 42 °C for 15 min. In addition, uptake of the drug released from TSP liposomes by cancer cells was enhanced by ultrasound irradiation. In a cell injury assay using doxorubicin (DOX)-loaded TSP liposomes and ultrasound irradiation, cell viability of HepG2 cells at 6 h after ultrasound irradiation (1 MHz, 0.5 W/cm(2) for 30 s) with DOX-loaded TSP liposomes (TSP/lipid ratio=1) was 60%, which was significantly lower than that of the control conditions such as DOX-loaded TSP liposomes alone and DOX-loaded intact liposomes under ultrasound irradiation. Copyright © 2013 Elsevier B.V. All rights reserved.

Renal-targeted delivery of triptolide by entrapment in pegylated TRX-20-modified liposomes.

Science.gov (United States)

Yuan, Zhi-Xiang; Jia, Lu; Lim, Lee Yong; Lin, Ju-Chun; Shu, Gang; Zhao, Ling; Ye, Gang; Liang, Xiao-Xia; Ji, Hongming; Fu, Hua-Lin

2017-01-01

Previously, 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20)-modified liposomes were reported to specifically target mesangial cells (MCs) in glomeruli. To further gain a better understanding of the characteristics and potential application for glomerular diseases of TRX-20-modified liposomes, we synthesized TRX-20 and prepared TRX-20-modified liposomes (TRX-LPs) with different molar ratios - 6% (6%-TRX-LP), 11% (11%-TRX-LP), and 14% (14%-TRX-LP) - of TRX-20 to total lipid in the present study. All TRX-LPs exhibited concentration-dependent toxicity against the MCs at a lipid concentration ranging from 0.01 to 1.0 mg/mL with IC 50 values of 3.45, 1.13, and 0.55 mg/mL, respectively. Comparison of the cell viability of TRX-LPs indicated that high levels of TRX-20 caused severe cell mortality, with 11%-TRX-LP showing the higher cytoplasmic accumulation in the MCs. Triptolide (TP) as a model drug was first loaded into 11%-TRX-LP and the liposomes were further modified with PEG 5000 (PEG-TRX-TP-LP) in an attempt to prolong their circulation in blood and enhance TP-mediated immune suppression. Due to specific binding to MCs, PEG-TRX-TP-LP undoubtedly showed better anti-inflammatory action in vitro, evidenced by the inhibition of release of nitric oxide (NO) and tumor necrosis factor-α from lipopolysaccharide-stimulated MCs, compared with free TP at the same dose. In vivo, the PEG-TRX-TP-LP effectively attenuated the symptoms of membranous nephropathic (MN) rats and improved biochemical markers including proteinuria, serum cholesterol, and albumin. Therefore, it can be concluded that the TRX-modified liposome is an effective platform to target the delivery of TP to glomeruli for the treatment of MN.

Accurate pKa calculation of the conjugate acids of alkanolamines, alkaloids and nucleotide bases by quantum chemical methods.

Science.gov (United States)

Gangarapu, Satesh; Marcelis, Antonius T M; Zuilhof, Han

2013-04-02

The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum model (CPCM) and universal solvation models (SMD, SM8). G3, SCS-MP2 and M11-L methods coupled with SMD and SM8 solvation models perform well for alkanolamines with mean unsigned errors below 0.20 pKa units, in all cases. Extending this method to the pKa calculation of 35 nitrogen-containing compounds spanning 12 pKa units showed an excellent correlation between experimental and computational pKa values of these 35 amines with the computationally low-cost SM8/M11-L density functional approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combretastatin A4/poly(L-glutamic acid-graft-PEG conjugates self-assembled to nanoparticles

Directory of Open Access Journals (Sweden)

Yang Ou

2018-03-01

Full Text Available Combretastatin A4 (CA4 possesses varying ability to cause vascular disruption in tumors, while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4 (CA4-PL was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid-graft-polyethylene glycol (PLG-g-PEG via Yamaguchi reaction. The obtained CA4-PL was characterized by 1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80~120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy. Keywords: Combretastatin A4, Macromolecular conjugate, Poly(L-glutamic acid-graft-polyethylene glycol, Self-assemble, Nanoparticles

The Adsorption Study of Aflatoxin B1 by Nanocellulose Conjugated with Aptamer in acidic, alkali, and Neutral Conditions

Directory of Open Access Journals (Sweden)

T Mirdehghan

2016-03-01

Full Text Available Introduction: Aflatoxin leads to liver cancer, its removal in the foodstuff is very important. The aim of this study is to investigate the adsorption of aflatoxin B1 by nanocellulose conjugated with aptamer in acidic, alkali, and neutral conditions. Methods: First, nanocellulose was synthesized by acid hydrolysis and then conjugated with aptamer by cross-linker. Then, serial concentrations of conjugated nanocellulose (0.6, 1.25, 2.5, 5, and 10 mg/mL were separately mixed with aflatoxin solution (1000µg/mL, and incubated at  37 °C for 0.5 h at pH of 1, 7, and 13. Then, the percentage of aflatoxin adsorption was measured at 340 nm.   Results: The decrease of pH led to increase of adsorption up to 40%. Statistically, there was significant difference between the quantity of adsorption at acidic condition and the quantity of adsorption at alkali and neutral conditions (P<0.05. Conclusion: Aflatoxin could be adsorbed by conjugated nanocellulose, and this power of adsorption is increased at acidic condition.

Tumor-targeted Nanobullets: Anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment.

Science.gov (United States)

van der Meel, Roy; Oliveira, Sabrina; Altintas, Isil; Haselberg, Rob; van der Veeken, Joris; Roovers, Rob C; van Bergen en Henegouwen, Paul M P; Storm, Gert; Hennink, Wim E; Schiffelers, Raymond M; Kok, Robbert J

2012-04-30

The epidermal growth factor receptor (EGFR) is a validated target for anti-cancer therapy and several EGFR inhibitors are used in the clinic. Over the years, an increasing number of studies have reported on the crosstalk between EGFR and other receptors that can contribute to accelerated cancer development or even acquisition of resistance to anti-EGFR therapies. Combined targeting of EGFR and insulin-like growth factor 1 receptor (IGF-1R) is a rational strategy to potentiate anti-cancer treatment and possibly retard resistance development. In the present study, we have pursued this by encapsulating the kinase inhibitor AG538 in anti-EGFR nanobody-liposomes. The thus developed dual-active nanobody-liposomes associated with EGFR-(over)expressing cells in an EGFR-specific manner and blocked both EGFR and IGF-1R activation, due to the presence of the EGFR-blocking nanobody EGa1 and the anti-IGF-1R kinase inhibitor AG538 respectively. AG538-loaded nanobody-liposomes induced a strong inhibition of tumor cell proliferation even upon short-term exposure followed by a drug-free wash-out period. Therefore, AG538-loaded nanobody-liposomes are a promising anti-cancer formulation due to efficient intracellular delivery of AG538 in combination with antagonistic and downregulating properties of the EGa1 nanobody-liposomes. Copyright © 2011 Elsevier B.V. All rights reserved.

Power system state estimation using an iteratively reweighted least squares method for sequential L{sub 1}-regression

Energy Technology Data Exchange (ETDEWEB)

Jabr, R.A. [Electrical, Computer and Communication Engineering Department, Notre Dame University, P.O. Box 72, Zouk Mikhael, Zouk Mosbeh (Lebanon)

2006-02-15

This paper presents an implementation of the least absolute value (LAV) power system state estimator based on obtaining a sequence of solutions to the L{sub 1}-regression problem using an iteratively reweighted least squares (IRLS{sub L1}) method. The proposed implementation avoids reformulating the regression problem into standard linear programming (LP) form and consequently does not require the use of common methods of LP, such as those based on the simplex method or interior-point methods. It is shown that the IRLS{sub L1} method is equivalent to solving a sequence of linear weighted least squares (LS) problems. Thus, its implementation presents little additional effort since the sparse LS solver is common to existing LS state estimators. Studies on the termination criteria of the IRLS{sub L1} method have been carried out to determine a procedure for which the proposed estimator is more computationally efficient than a previously proposed non-linear iteratively reweighted least squares (IRLS) estimator. Indeed, it is revealed that the proposed method is a generalization of the previously reported IRLS estimator, but is based on more rigorous theory. (author)

Catalyst-Free Conjugation and In Situ Quantification of Nanoparticle Ligand Surface Density Using Fluorogenic Cu-Free Click Chemistry

DEFF Research Database (Denmark)

Jølck, Rasmus Irming; Sun, Honghao; Berg, Rolf Henrik

2011-01-01

A highly efficient method for functionalizing nanoparticles and directly quantifying conjugation efficiency and ligand surface density has been developed. Attachment of 3-azido-modifed RGD-peptides to PEGylated liposomes was achieved by using Cu-free click conditions. Upon coupling a fluorophore ...

Effect of chitosan coating on the characteristics of DPPC liposomes

Directory of Open Access Journals (Sweden)

Mohsen M. Mady

2010-07-01

Full Text Available Because it is both biocompatible and biodegradable, chitosan has been used to provide a protective capsule in new drug formulations. The present work reports on investigations into some of the physicochemical properties of chitosan-coated liposomes, including drug release rate, transmission electron microscopy (TEM, zeta potential and turbidity measurement. It was found that chitosan increases liposome stability during drug release. The coating of DPPC liposomes with a chitosan layer was confirmed by electron microscopy and the zeta potential of liposomes. The coating of liposomes by chitosan resulted in a marginal increase in the size of the liposomes, adding a layer of (92 ± 27.1 nm. The liposomal zeta potential was found to be increasingly positive as chitosan concentration increased from 0.1% to 0.3% (w/v, before stabilising at a relatively constant value. Turbidity studies revealed that the coating of DPPC liposomes with chitosan did not significantly modify the main phase transition temperature of DPPC at examined chitosan concentrations. The appropriate combination of liposomal and chitosan characteristics may produce liposomes with specific, prolonged and controlled release.

Prolonged hypoglycemic effect in diabetic dogs due to subcutaneous administration of insulin in liposomes

International Nuclear Information System (INIS)

Stevenson, R.W.; Patel, H.M.; Parsons, J.A.; Ryman, B.E.

1982-01-01

The biologic action of insulin entrapped in liposomes (phospholipid vesicles) has been investigated following subcutaneous injection to dogs made diabetic with a combination of alloxan and streptozotocin. The fate of the liposomally entrapped material was determined by injecting rats subcutaneously with either 125 I-insulin or the labeled polysaccharide 14 C-inulin, incorporated in liposomes labeled with 3 H-cholesterol. Injection of liposome insulin (0.75 U/kg) to five diabetic dogs resulted in a mean (+/- SEM) blood glucose fall from 16.4 +/- 0.8 to 2.9 +/- 0.4 mmol/L. The glucose level had still not returned to baseline after 24 h and, correspondingly, immunoreactive insulin (IRI) could still be detected in frozen and thawed plasma 24 h after injection. In contrast, the hypoglycemic effect of the same dose of free insulin with or without empty liposomes virtually ended within 8 h and IRI levels returned to baseline by 3 h after injection. In experiments on rats with liposomally entrapped 125 I-insulin or 14 C-inulin the proportion of the injected dose of tracer recoverable by excision of the injection site remained constant after about 1 h and 70% of the dose was still fixed in subcutaneous tissue for at least 5 h thereafter. When the plasma collected 3 h after subcutaneous injection of labeled liposomes containing 125 I-insulin was passed through a column of Sepharose 6B, 50-75% of the 125 I-activity was found in the fractions associated with intact liposomes. One possibility for the persistence of the hypoglycemic effect and of measurable IRI following injection of liposome insulin could be the presence of intact liposomes in the circulation for many hours after adsorption had ceased

LS1 Report: short-circuit tests

CERN Multimedia

Katarina Anthony

2014-01-01

As the LS1 draws to an end, teams move from installation projects to a phase of intense testing. Among these are the so-called 'short-circuit tests'. Currently under way at Point 7, these tests verify the cables, the interlocks, the energy extraction systems, the power converters that provide current to the superconducting magnets and the cooling system.   Thermal camera images taken during tests at point 4 (IP4). Before putting beam into the LHC, all of the machine's hardware components need to be put to the test. Out of these, the most complicated are the superconducting circuits, which have a myriad of different failure modes with interlock and control systems. While these will be tested at cold - during powering tests to be done in August - work can still be done beforehand. "While the circuits in the magnets themselves cannot be tested at warm, what we can do is verify the power converter and the circuits right up to the place the cables go into the magn...

LS1 Report: onwards and upwards

CERN Multimedia

Katarina Anthony

2013-01-01

For the first time since 2008, engineers have taken most of the LHC’s electromagnetic circuits up to the current needed for magnets to guide beams around the machine at the design energy of 7 TeV. This first phase of intensive tests has been instrumental for the planning of upcoming machine interventions.   All of the circuits in Sector 67 were powered to a 7 TeV equivalent current, with the main circuits (to be consolidated during LS1) powered at 4 TeV. Around 1700 magnet circuits are needed to circulate beams in the LHC. Come 2015, each and every one of these circuits will have to be able to accept their 7 TeV equivalent current. For the LHC’s 24 main dipole and quadrupole circuits, this will mean the consolidation of all their interconnections. But what about the rest of the LHC’s circuits that had been mostly operating at around 60% of the nominal value? How will they handle the ramp-up to design energy? Those questions were asked and answered during the rec...

LS1 Report: LHCb's early Christmas

CERN Multimedia

Katarina Anthony

2014-01-01

Accelerator chain up and running... CCC Operators back at their desks... all telltale signs of the start of Run 2! For the experiments, that means there are just a few short weeks left for them to prepare for beams. Over at LHCb, teams have kept ahead of the curve by focusing on new installations and improvements.   A delicate task: re-connecting the beam pipe in LHCb. From the primary detector services to the DAQ system to the high level trigger, November's injector test beams saw their way through a well-prepared LHCb experiment. “We set the transfer line tests as our deadline for the restart - the entire experiment had to be at nominal position and conditions,” says Eric Thomas, LHCb deputy Technical Coordinator and LHCb LS1 Project Coordinator. “Achieving this was a major milestone for the collaboration. If beam were to come tomorrow, we would be ready.” The injector tests gave the LHCb team a chance to synchronise their detectors, and to al...

A novel theranostic nanobioconjugate. "1"2"5/"1"3"1I labeled phenylalanine conjugated boron nitride nanotubes

International Nuclear Information System (INIS)

Ozge Kozgus Guldu; Perihan Unak; Suna Timur

2017-01-01

Here we report the synthesis of boron nitride nanotubes (BNNTs) via a chemical vapor deposition method, as potential agents for boron neutron capture therapy. BNNTs were functionalized with PAMAM[G-2] dendrimer and then, conjugated with l-Phe using EDC/NHS. After that, BNNTs were radiolabeled with "1"2"5/"1"3"1I, which are commonly used for both therapy and diagnosis in clinical and pre-clinical studies. BNNTs were radiolabeled with a maximum yield with "1"2"5/"1"3"1I in compared with 4-borono-l-phenyalanine which is currently used as a commercial drug. Radiolabeling parameters were optimized with thin layer radiochromatography and high performance liquid radiochromatography. BNNTs are promising nanobioconjugates as new theranostic agents. (author)

EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

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Romanova OA

2016-12-01

Full Text Available Introduction. With the transport links development there is rather important issue respiratory viral infections spread, especially influenza. The only method controlling influenza is vaccination. Search and development effective and safe vaccines is important. Material and methods. In base SO "Mechnikov Institute Microbiology and Immunology National Ukrainian Academy Medical Sciences" in the scientific theme "Developing new approaches to creating viral vaccines and study specific activity depending of type and degree component`s modification" was created several experimental influenza vaccine with subsequent component`s modification for selecting the most optimal pattern of safety and immunogenicity. In assessing the influenza vaccine safety is using a few criteria, including, reactivity, as measured by the frequency of local and systemic adverse (negative effects, which due to its introduction, and for lipid content drugs, ability to influence oxidation processes. At present study phase was determined: a systemic reaction and local reaction of delayed-type hypersensitivity (foot pad swelling assay;b lipids and proteins peroxidation processes after administration officinal and experimental vaccines (content protein’s carbonyl groups, lipid’s hydroperoxides, activity of glutathione-peroxidase.Study objects were trivalent seasonal influenza vaccine, "Vaxigrip" (Sanofi Pasteur, S.A., France, "Inflexal V" (Biotech Ltd. Berne, Switzerland and experimental vaccine samples. Highest immunogenicity vaccines had undergone improvements and modifications using adjuvant systems and acylation influenza proteins. Liposomes 2 – the experimental influenza vaccine with a liposome negative charge and antigenic composition like split vaccines "Vaksihryp". Liposomes 2.1 - the adjuvantexperimental influenza vaccine with modifications liposomal components (etoniy and chlorophyllipt molecules embedded in liposomal membrane. Liposomes 2.2 - the adjuvant

Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

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Jain PP

2014-07-01

Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn's disease.

Science.gov (United States)

Robertson, Jack; Haas, Carolin T; Pele, Laetitia C; Monie, Tom P; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E; Powell, Jonathan J

2016-05-26

Crohn's disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn's disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn's disease show selective failure in PD-L1 expression. Therefore, in Crohn's disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease.

Ultrasound triggered drug delivery with liposomal nested microbubbles.

Science.gov (United States)

Wallace, N; Wrenn, S P

2015-12-01

When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa). Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation optimization and in vivo proof-of-concept study of thermosensitive liposomes balanced by phospholipid, elastin-like polypeptide, and cholesterol.

Directory of Open Access Journals (Sweden)

Sun Min Park

Full Text Available One application of nanotechnology in medicine that is presently being developed involves a drug delivery system (DDS employing nanoparticles to deliver drugs to diseased sites in the body avoiding damage of healthy tissue. Recently, the mild hyperthermia-triggered drug delivery combined with anticancer agent-loaded thermosensitive liposomes was widely investigated. In this study, thermosensitive liposomes (TSLs, composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000] (DSPE-PEG, cholesterol, and a fatty acid conjugated elastin-like polypeptide (ELP, were developed and optimized for triggered drug release, controlled by external heat stimuli. We introduced modified ELP, tunable for various biomedical purposes, to our thermosensitive liposome (e-TSL to convey a high thermoresponsive property. We modulated thermosensitivity and stability by varying the ratios of e-TSL components, such as phospholipid, ELP, and cholesterol. Experimental data obtained in this study corresponded to results from a simulation study that demonstrated, through the calculation of the lateral diffusion coefficient, increased permeation of the lipid bilayer with higher ELP concentrations, and decreased permeation in the presence of cholesterol. Finally, we identified effective drug accumulation in tumor tissues and antitumor efficacy with our optimized e-TSL, while adjusting lag-times for systemic accumulation.

Copper-64 labeled liposomes for imaging bone marrow

International Nuclear Information System (INIS)

Lee, Sang-gyu; Gangangari, Kishore; Kalidindi, Teja Muralidhar; Punzalan, Blesida; Larson, Steven M.; Pillarsetty, Naga Vara Kishore

2016-01-01

Introduction: Bone marrow is the soft tissue compartment inside the bones made up of hematopoietic cells, adipocytes, stromal cells, phagocytic cells, stem cells, and sinusoids. While [ 18 F]-FLT has been utilized to image proliferative marrow, to date, there are no reports of particle based positron emission tomography (PET) imaging agents for imaging bone marrow. We have developed copper-64 labeled liposomal formulation that selectively targets bone marrow and therefore serves as an efficient PET probe for imaging bone marrow. Methods: Optimized liposomal formulations were prepared with succinyl PE, DSPC, cholesterol, and mPEG-DSPE (69:39:1:10:0.1) with diameters of 90 and 140 nm, and were doped with DOTA-Bn-DSPE for stable 64 Cu incorporation into liposomes. Results: PET imaging and biodistribution studies with 64 Cu-labeled liposomes indicate that accumulation in bone marrow was as high as 15.18 ± 3.69%ID/g for 90 nm liposomes and 7.01 ± 0.92%ID/g for 140 nm liposomes at 24 h post-administration. In vivo biodistribution studies in tumor-bearing mice indicate that the uptake of 90 nm particles is approximately 0.89 ± 0.48%ID/g in tumor and 14.22 ± 8.07%ID/g in bone marrow, but respective values for Doxil® like liposomes are 0.83 ± 0.49%ID/g and 2.23 ± 1.00%ID/g. Conclusion: Our results indicate that our novel PET labeled liposomes target bone marrow with very high efficiency and therefore can function as efficient bone marrow imaging agents.

Enhanced antidepressant-like effects of the macromolecule trefoil factor 3 by loading into negatively charged liposomes

Directory of Open Access Journals (Sweden)

Qin J

2014-11-01

Full Text Available Jing Qin,1 Xu Yang,1–3 Jia Mi,4 Jianxin Wang,1 Jia Hou,1,2 Teng Shen,1 Yongji Li,2 Bin Wang,4 Xuri Li,4 Weili Zhu5 1Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 2Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, 3Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 4Binzhou Medical University, Yantai, 5National Institute on Drug Dependence, Peking University, Beijing, People’s Republic of China Abstract: Immunocytes, mainly neutrophils and monocytes, exhibit an intrinsic homing property, enabling them to migrate to sites of injury and inflammation. They can thus act as Trojan horses carrying concealed drug cargoes while migrating across impermeable barriers to sites of disease, especially the blood–brain barrier (BBB. In this study, to target circulating phagocytic cells, we formulated negatively charged nanosize liposomes and loaded trefoil factor 3 (TFF3 into liposomes by the pH-gradient method. According to the optimized formulation (5:1.5 of lipid to cholesterol, 10:1 of lipid to drug, 10 mg/mL of lipid concentration, and 10 mmol/L of phosphate-buffered saline, 44.47% entrapment efficiency was obtained for TFF3 liposomes with 129.6 nm particle size and –36.6 mV zeta potential. Compared with neutrally charged liposomes, the negatively charged liposomes showed a strong binding capacity with monocytes and were effectively carried by monocytes to cross the BBB in vitro. Furthermore, enhanced antidepressant-like effects were found in the tail-suspension and forced-swim tests in mice, as measured by decreased immobility time, as well as increased swimming time and reduced immobility in rats. These results suggested that negatively charged liposomes could improve the behavioral responses of TFF3, and our study opens up a new way for the development of

Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro.

Science.gov (United States)

Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Kalle, Wouter H J

2004-11-01

Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting. We show that liposomes are effective in the protection of adenovirus from neutralising antibody and that the conjugation of these complexes to microspheres augments the level of protection. This study further reveals that previously neutralised adenovirus may still be transported into the cell via liposome-cell interactions and is still capable of expressing its genes, making this vector an effective tool for circumvention of the humoral immune response. We also looked at possible side effects of using the complexes, namely increases in cytotoxicity and reductions in transfection efficiency. Our results showed that varying the liposome:adenovirus ratio can reduce the cytotoxicity of the vector as well as increase the transfection efficiency. In addition, in cell lines that are adenoviral competent, transfection efficiencies on par with uncomplexed adenoviral vectors were achievable with the combination vector.

Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

Science.gov (United States)

Mady, Mohsen M.; Elshemey, Wael M.

2011-06-01

Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

SCC-TB, DFT/B3LYP, MP2, AM1, PM3 and RHF study of ethylene oxide and propylene oxide structures, VA and VCD spectra

DEFF Research Database (Denmark)

Jalkanen, Karl J.; Frimand, Kenneth

2002-01-01

-binding method for equilibrium structures, VA and VCD spectra of ethylene oxide and propylene oxide in the gas-phase. Comparison to conventional methods AM1, PM3, MP2, RHF and DFT/B3LYP is carried out. We report results over a wider range of frequencies than previous work. In particular, we find indications...... that the self-consistent-charge tight-binding method, combined with DFT/B3LYP atomic polar tensors and atomic axial tensors, compares favourably with competing methods tendency to overestimate the location of spectral peaks with respect to frequencies, the latter observation being most pronounced in the higher...... frequency regions. Our findings produce additional support for the self-consistent-charge tight-binding method as a fast computational method for small and larger molecules, however, also that improved parameterisations are needed to reach accuracies of MP2 and DFT/B3LYP. (C) 2002 Elsevier Science B.V. All...

Peptide-Mediated Liposomal Drug Delivery System Targeting Tumor Blood Vessels in Anticancer Therapy

Directory of Open Access Journals (Sweden)

Han-Chung Wu

2010-01-01

Full Text Available Solid tumors are known to recruit new blood vessels to support their growth. Therefore, unique molecules expressed on tumor endothelial cells can function as targets for the antiangiogenic therapy of cancer. Current efforts are focusing on developing therapeutic agents capable of specifically targeting cancer cells and tumor-associated microenvironments including tumor blood vessels. These therapies hold the promise of high efficacy and low toxicity. One recognized strategy for improving the therapeutic effectiveness of conventional chemotherapeutics is to encapsulate anticancer drugs into targeting liposomes that bind to the cell surface receptors expressed on tumor-associated endothelial cells. These anti-angiogenic drug delivery systems could be used to target both tumor blood vessels as well as the tumor cells, themselves. This article reviews the mechanisms and advantages of various present and potential methods using peptide-conjugated liposomes to specifically destroy tumor blood vessels in anticancer therapy.

S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model

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Xiaobo eFan

2015-10-01

Full Text Available S-thanatin (Ts was a short antimicrobial peptide with selective antibacterial activity. In this study, we aimed to design a drug carrier with specific bacterial targeting potential. The positively charged Ts was modified onto the liposome surface by linking Ts to the constituent lipids via a PEG linker. The benefits of this design were evaluated by preparing a series of liposomes and comparing their biological effects in vitro and in vivo. The particle size and Zeta potential of the constructed liposomes were measured with a Zetasizer Nano ZS system and a confocal laser scanning microscope (CLSM. The in vitro drug delivery potential was evaluated by measuring the cellular uptake of encapsulated levofloxacin using HPLC. Ts-linked liposome or its conjugates with quantum dots favored bacterial cells, and increased the bacterial uptake of levofloxacin. In antimicrobial assays, the Ts and levofloxacin combination showed a synergistic effect, and Ts-LPs-LEV exhibited excellent activity against the quality control stain Klebsiella pneumoniae ATCC 700603 and restored the susceptibility of multidrug-resistant K. pneumoniae clinical isolates to levofloxacin in vitro. Furthermore, Ts-LPs-LEV markedly reduced the lethality rate of the septic shock and resulted in rapid bacterial clearance in mouse models receiving clinical MDR isolates. These results suggest that the Ts-functionalized liposome may be a promising antibiotic delivery system for clinical infectious disorders caused by MDR bacteria, in particular the sepsis related diseases.

Arabidopsis dynamin-related protein 1A polymers bind, but do not tubulate, liposomes

International Nuclear Information System (INIS)

Backues, Steven K.; Bednarek, Sebastian Y.

2010-01-01

The Arabidopsis dynamin-related protein 1A (AtDRP1A) is involved in endocytosis and cell plate maturation in Arabidopsis. Unlike dynamin, AtDRP1A does not have any recognized membrane binding or protein-protein interaction domains. We report that GTPase active AtDRP1A purified from Escherichia coli as a fusion to maltose binding protein forms homopolymers visible by negative staining electron microscopy. These polymers interact with protein-free liposomes whose lipid composition mimics that of the inner leaflet of the Arabidopsis plasma membrane, suggesting that lipid-binding may play a role in AtDRP1A function. However, AtDRP1A polymers do not appear to assemble and disassemble in a dynamic fashion and do not have the ability to tubulate liposomes in vitro, suggesting that additional factors or modifications are necessary for AtDRP1A's in vivo function.

Kıl Keçi ve Saanen x Kıl Keçi Melezlerinin (F1, G1, Çiftçi Şartlarında Süt Verim Özellikleri Bakımından Karşılaştırılması

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Hilal Tozlu Çelik

2014-11-01

Full Text Available Bu araştırma, Amasya ili Sarılar köyü, özel bir işletmede 2011-2012 yılları arasında yetiştirilen Saanen x Kıl keçi melezleri (F1, G1 ve Kıl keçilerinde süt verimi özellikleri üzerine genotip, yıl ve yaş faktörlerinin etkisini ortaya koymak amacıyla yapılmıştır. Araştırmada 2011 ve 2012 yıllarında günlük ortalama süt verimi (GOSV, laktasyon süresi (LS ve laktasyon süt verimi (LSV üzerine genotipin etkili olduğu bulunmuştur. 2011 yılında yaşın tüm genotiplerde GOSV ve LSV etkisinin olduğu tespit edilmiştir. Araştırmada 2012 yılında yaşın tüm genotiplerde GOSV ve LS'ne etkisinin olduğu saptanmıştır. F1 genotipinde ve Kıl keçilerde yılın GOSV, LSV ve LS üzerine etkili olduğu bulunmuştur. G1 genotipinde yılın sadece LS üzerine etkisi olduğu saptanmıştır. Sonuç olarak çiftçi şartlarında yetiştirilen Saanen x Kıl keçi F1 ve G1 genotipinin süt verim özelliklerinin Kıl keçilerden daha yüksek olduğu söylenebilir.

A turn-on chemiluminescence biosensor for selective and sensitive detection of adenosine based on HKUST-1 and QDs-luminol-aptamer conjugates.

Science.gov (United States)

Lin, Yanna; Dai, Yuxue; Sun, Yuanling; Ding, Chaofan; Sun, Weiyan; Zhu, Xiaodong; Liu, Hao; Luo, Chuannan

2018-05-15

In this work, HKUST-1 and QDs-luminol-aptamer conjugates were prepared. The QDs-luminol-aptamer conjugates can be adsorbed by graphene oxide through π-π conjugation. When the adenosine was added, the QDs-luminol-aptamer conjugates were released from magnetic graphene oxide (MGO), the chemiluminescent switch was turned on. It was reported that HKUST-1 can catalyze the chemiluminescence reaction of luminol-H 2 O 2 system in an alkaline medium, and improve the chemiluminescence resonance energy transfer (CRET) between chemiluminescence and QDs indirectly. Thus, the adenosine can be detected sensitively. Based on this phenomenon, the excellent platform for detection of adenosine was established. Under the optimized conditions, the linear detection range for adenosine was 1.0 × 10 -12 -2.2 × 10 -10 mol/L with a detection limit of 2.1 × 10 -13 mol/L. The proposed method was successfully used for adenosine detection in biological samples. Copyright © 2018 Elsevier B.V. All rights reserved.

Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

International Nuclear Information System (INIS)

Cai, Demin; Li, Hongji; Zhou, Bo; Han, Liqiang; Zhang, Xiaomei; Yang, Guoyu; Yang, Guoqing

2012-01-01

Highlights: ► Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. ► Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. ► Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor α (TNFα) and the positive regulator Peroxisome Proliferator-Activated Receptor-γ (PPARγ) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

Preliminary results on clinical effects of probiotic Lactobacillus salivarius LS01 in children affected by atopic dermatitis.

Science.gov (United States)

Niccoli, Antonio A; Artesi, Anna L; Candio, Francesco; Ceccarelli, Sara; Cozzali, Rita; Ferraro, Luigi; Fiumana, Donatella; Mencacci, Manuela; Morlupo, Maurizio; Pazzelli, Paola; Rossi, Laura; Toscano, Marco; Drago, Lorenzo

2014-01-01

The goal of this study was to evaluate the clinical efficacy of an intake of Lactobacillus salivarius LS01 (DSM 22775) for the treatment of atopic dermatitis (AD) in children. AD is an inflammatory and pruritic chronic relapsing skin disorder with multifactorial etiopathology. Some evidence suggests that probiotics may improve AD by modulating the immune system and the composition of intestinal microbiota. A total of 43 patients aged from 0 to 11 years were enrolled in the study (M/F ratio=1:1) and treated with the probiotic strain L. salivarius LS01. Clinical efficacy of probiotic treatment was assessed from baseline by changes in itch index and in the objective SCORAD/SCORAD index. Patients being given probiotic treatment showed a significant improvement in clinical parameters (SCORAD and itch values) from baseline. The reduction in SCORAD and itch index observed after 4 weeks of treatment also persisted after the cessation of probiotic supplementation. L. salivarius LS01 seems to be able to improve the quality of life of children affected by AD and, as a consequence, it may have promising clinical and research implications.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

Directory of Open Access Journals (Sweden)

Ding Y

2015-10-01

Full Text Available Yuan Ding,1,* Dan Sun,1,* Gui-Ling Wang,1 Hong-Ge Yang,1 Hai-Feng Xu,1 Jian-Hua Chen,2 Ying Xie,1,3 Zhi-Qiang Wang4 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 2School of Medicine, Jianghan University, Wuhan, 3State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, People’s Republic of China; 4Department of Chemistry and Biochemistry, Kent State University Geauga, Burton, OH, USA *These authors contributed equally to this work Abstract: Cell-penetrating peptides (CPPs as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into

Astragaloside IV liposomes ameliorates adriamycin-induced ...

African Journals Online (AJOL)

Methods: The rats were given a single tail intravenous injection of adriamycin (6 mg/kg) within 1 week, and then divided into four groups including normal, model, benazepril and astragaloside IV liposomes group. They were all orally administered dosage of benazepril and astragaloside IV liposomes once daily for 8 weeks.

ATLAS TDAQ application gateway upgrade during LS1

CERN Document Server

KOROL, A; The ATLAS collaboration; BOGDANCHIKOV, A; BRASOLIN, F; CONTESCU, A C; DUBROV, S; HAFEEZ, M; LEE, C J; SCANNICCHIO, D A; TWOMEY, M; VORONKOV, A; ZAYTSEV, A

2014-01-01

The ATLAS Gateway service is implemented with a set of dedicated computer nodes to provide a fine-grained access control between CERN General Public Network (GPN) and ATLAS Technical Control Network (ATCN). ATCN connects the ATLAS online farm used for ATLAS Operations and data taking, including the ATLAS TDAQ (Trigger and Data Aquisition) and DCS (Detector Control System) nodes. In particular, it provides restricted access to the web services (proxy), general login sessions (via SSH and RDP protocols), NAT and mail relay from ATCN. At the Operating System level the implementation is based on virtualization technologies. Here we report on the Gateway upgrade during Long Shutdown 1 (LS1) period: it includes the transition to the last production release of the CERN Linux distribution (SLC6), the migration to the centralized configuration management system (based on Puppet) and the redesign of the internal system architecture.

Optimization of drug loading to improve physical stability of paclitaxel-loaded long-circulating liposomes.

Science.gov (United States)

Kannan, Vinayagam; Balabathula, Pavan; Divi, Murali K; Thoma, Laura A; Wood, George C

2015-01-01

The effect of formulation and process parameters on drug loading and physical stability of paclitaxel-loaded long-circulating liposomes was evaluated. The liposomes were prepared by hydration-extrusion method. The formulation parameters such as total lipid content, cholesterol content, saturated-unsaturated lipid ratio, drug-lipid ratio and process parameters such as extrusion pressure and number of extrusion cycles were studied and their impact on drug loading and physical stability was evaluated. A proportionate increase in drug loading was observed with increase in the total phospholipid content. Cholesterol content and saturated lipid content in the bilayer showed a negative influence on drug loading. The short-term stability evaluation of liposomes prepared with different drug-lipid ratios demonstrated that 1:60 as the optimum drug-lipid ratio to achieve a loading of 1-1.3 mg/mL without the risk of physical instability. The vesicle size decreased with an increase in the extrusion pressure and number of extrusion cycles, but no significant trends were observed for drug loading with changes in process pressure or number of cycles. The optimization of formulation and process parameters led to a physically stable formulation of paclitaxel-loaded long-circulating liposomes that maintain size, charge and integrity during storage.

Overcoming cellular and tissue barriers to improve liposomal drug delivery

Science.gov (United States)

Kohli, Aditya G.

Forty years of liposome research have demonstrated that the anti-tumor efficacy of liposomal therapies is, in part, driven by three parameters: 1) liposome formulation and lipid biophysics, 2) accumulation and distribution in the tumor, and 3) release of the payload at the site of interest. This thesis outlines three studies that improve on each of these delivery steps. In the first study, we engineer a novel class of zwitterlipids with an inverted headgroup architecture that have remarkable biophysical properties and may be useful for drug delivery applications. After intravenous administration, liposomes accumulate in the tumor by the enhanced permeability and retention effect. However, the tumor stroma often limits liposome efficacy by preventing distribution into the tumor. In the second study, we demonstrate that depletion of hyaluronan in the tumor stroma improves the distribution and efficacy of DoxilRTM in murine 4T1 tumors. Once a liposome has distributed to the therapeutic site, it must release its payload over the correct timescale. Few facile methods exist to quantify the release of liposome therapeutics in vivo. In the third study, we outline and validate a simple, robust, and quantitative method for tracking the rate and extent of release of liposome contents in vivo. This tool should facilitate a better understanding of the pharmacodynamics of liposome-encapsulated drugs in animals. This work highlights aspects of liposome behavior that have prevented successful clinical translation and proposes alternative approaches to improve liposome drug delivery.

Data on genome analysis of Bacillus velezensis LS69.

Science.gov (United States)

Liu, Guoqiang; Kong, Yingying; Fan, Yajing; Geng, Ce; Peng, Donghai; Sun, Ming

2017-08-01

The data presented in this article are related to the published entitled "Whole-genome sequencing of Bacillus velezensis LS69, a strain with a broad inhibitory spectrum against pathogenic bacteria" (Liu et al., 2017) [1]. Genome analysis revealed B. velezensis LS69 has a good potential for biocontrol and plant growth promotion. This article provides an extended analysis of the genetic islands, core genes and amylolysin loci of B. velezensis LS69.

Data on genome analysis of Bacillus velezensis LS69

OpenAIRE

Liu, Guoqiang; Kong, Yingying; Fan, Yajing; Geng, Ce; Peng, Donghai; Sun, Ming

2017-01-01

The data presented in this article are related to the published entitled “Whole-genome sequencing of Bacillus velezensis LS69, a strain with a broad inhibitory spectrum against pathogenic bacteria” (Liu et al., 2017) [1]. Genome analysis revealed B. velezensis LS69 has a good potential for biocontrol and plant growth promotion. This article provides an extended analysis of the genetic islands, core genes and amylolysin loci of B. velezensis LS69.

Endogenous Auxin Profile in the Christmas Rose (Helleborus niger L.) Flower and Fruit: Free and Amide Conjugated IAA

Czech Academy of Sciences Publication Activity Database

Brcko, A.; Pěnčík, Aleš; Magnus, V.; Prebeg, T.; Mlinaric, S.; Antunovic, J.; Lepeduš, H.; Cesar, V.; Strnad, Miroslav; Rolčík, Jakub; Salopek-Sondi, B.

2012-01-01

Roč. 31, č. 1 (2012), s. 63-78 ISSN 0721-7595 R&D Projects: GA AV ČR KAN200380801 Keywords : Auxin * Indole-3-acetic acid * Amide conjugates * Christmas rose * Helleborus niger L. * Flower and fruit development * Perianth greening * Peduncle elongation * Vascular system Subject RIV: EF - Botanics Impact factor: 1.990, year: 2012

Large-scale preparation of clove essential oil and eugenol-loaded liposomes using a membrane contactor and a pilot plant.

Science.gov (United States)

Sebaaly, Carine; Greige-Gerges, Hélène; Agusti, Géraldine; Fessi, Hatem; Charcosset, Catherine

2016-01-01

Based on our previous study where optimal conditions were defined to encapsulate clove essential oil (CEO) into liposomes at laboratory scale, we scaled-up the preparation of CEO and eugenol (Eug)-loaded liposomes using a membrane contactor (600 mL) and a pilot plant (3 L) based on the principle of ethanol injection method, both equipped with a Shirasu Porous Glass membrane for injection of the organic phase into the aqueous phase. Homogenous, stable, nanometric-sized and multilamellar liposomes with high phospholipid, Eug loading rates and encapsulation efficiency of CEO components were obtained. Saturation of phospholipids and drug concentration in the organic phase may control the liposome stability. Liposomes loaded with other hydrophobic volatile compounds could be prepared at large scale using the ethanol injection method and a membrane for injection.

Study on the performance of the Particle Identification Detectors at LHCb after the LHC First Long Shutdown (LS1)

CERN Document Server

Fontana, Marianna

2016-01-01

During the First Long Shutdown (LS1), the LHCb experiment has introduced major modification in the data-processing procedure and modified part of the detector to deal with the increased energy and the increased heavy-hadron production cross-section. In this contribution we review the performance of the particle identification detectors at LHCb, Rich, Calorimeters, and Muon system, after the LS1

CMS outreach event to close LS1

CERN Multimedia

Achintya Rao

2015-01-01

CMS opened its doors to about 700 students from schools near CERN, who visited the detector on 16 and 17 February during the last major CMS outreach event of LS1.   Pellentesque sapien mi, pharetra vitae, auctor eu, congue sed, turpis. Enthusiastic CMS guides spent a day and a half showing the equally enthusiastic visitors, aged 10 to 18, the beauty of CMS and particle physics. The recently installed wheelchair lift was called into action and enabled a visitor who arrived on crutches to access the detector cavern unimpeded.  The CMS collaboration had previously devoted a day to school visits after the successful “Neighbourhood Days” in May 2014 and, encouraged by the turnout, decided to extend an invitation to local schools once again. The complement of nearly 40 guides and crowd marshals was aided by a support team that coordinated the transportation of the young guests and received them at Point 5, where a dedicated safety team including first-aiders, security...

LS1 Report: the clouds are lifting

CERN Multimedia

Anaïs Schaeffer

2014-01-01

To combat the problem of electron clouds, which perturbate the environment of the particle beams in our accelerators, the Vacuum team have turned to amorphous carbon. This material is being applied to the interior of 16 magnets in the SPS during LS1 and will help prevent the formation of the secondary particles which are responsible for these clouds.   This photo shows the familiar coils of an SPS dipole magnet in brown. The vacuum chamber is the metallic rectangular part in the centre. The small wheeled device you can see in the vacuum chamber carries the hollow cathodes  along the length of the chamber. When a particle beam circulates at high energy in a vacuum chamber, it unavoidably generates secondary particles. These include electrons produced by the ionisation of residual molecules in the vacuum or indirectly generated by synchrotron radiation. When these electrons hit the surface of the vacuum chamber, they produce other electrons which, through an avalanche-like process, re...

COMPETENZA DIGITALE E GLOTTOTECNOLOGIE PER L’INSEGNANTE DI ITALIANO L2/LS

Directory of Open Access Journals (Sweden)

Diego Santalucia

2015-07-01

Full Text Available L’articolo, prendendo spunto da recenti progetti che spingono per un utilizzo sempre più esteso di tablet e strumenti digitali in classe, fa riferimento alla Raccomandazione del Parlamento Europeo e del Consiglio dell’Unione Europea (2006 per discutere alcuni degli elementi rappresentativi della “competenza digitale” che la Raccomandazione delinea. Alla luce di questi elementi si sviluppano alcune indicazioni sull’uso ragionato dei motori di ricerca e di alcune risorse offerte dalla rete, come Google Docs e Google Drive.Seguono una breve illustrazione di Edmodo, una piattaforma didattica social, e alcune indicazioni sull’utilizzo degli smartphone per l’accesso a risorse utili e semplici da condividere in classe. Sono tracciate alcune linee guida sulla gestione di risorse già accessibili in rete e che sono, quindi, a disposizione di quegli insegnanti di Italiano L2/LS che vogliano utilizzare sistemi di condivisione online a sostegno della didattica in presenza.Digital competence and digital language teaching for Italian L2/FL teachersThe article, inspired by recent projects that push for an ever-wider use of tablets and digital tools in the classroom, refers to the Recommendation of the European Parliament and of the Council of the European Union (2006 discusses some of the representative elements of “digital competence” that the Recommendation outlines. In light of these elements, some guidelines on the use of search engines and some resources offered by the network, such as Google Docs and Google Drive, are offered.This is followed by a brief description of Edmodo, a social learning platform, and information on the use of smartphones to access helpful resources that are easy to share in class. Finally, some guidelines on the management of resources already available on the Internet for Italian L2/FL teachers who want to use online sharing systems to support of frontal lessons are given.

Potentiation of ovarian OCa-1 tumor radioresponse by poly (L-glutamic acid)-paclitaxel conjugate

International Nuclear Information System (INIS)

Li Chun; Ke Shi; Wu Qingping; Tansey, Wayne; Hunter, Nancy; Buchmiller, Lara M.; Milas, Luka; Charnsangavej, Chusilp; Wallace, Sidney

2000-01-01

Purpose: It has been shown that paclitaxel (TXL) can strongly enhance tumor cells' sensitivity to radiation. We examined whether the radiosensitizing effect of paclitaxel can be further enhanced when it is delivered systemically as a polymer-drug conjugate that provides enhanced tumor uptake and prolonged release of TXL in the tumor. Methods and Materials: C3Hf/Kam mice bearing 8-mm murine ovarian OCa-1 tumors were treated with i.v.-injected Poly(L-glutamic acid)-paclitaxel (PG-TXL) at an equivalent TXL dose of 80 mg/kg, followed 24 h later by single doses of local radiation ranging from 5 to 15 Gy. To determine how long the radiopotentiation persisted at extended times after PG-TXL administration, mice with OCa-1 tumors were given i.v. PG-TXL and 4, 24, 48, 72, 120, or 168 h later their tumors were irradiated at a dose of 10 Gy. Antitumor activity was determined by delay in tumor growth. Cell cycle distribution was assayed using flow cytometry. Tumor vascular volume was estimated using Tc-99 m-labeled red blood cells. Results: PG-TXL strongly potentiated the radioresponse of the OCa-1 tumor. The enhancement factors ranged from 2.79 to 4.28, depending on radiation dose, when PG-TXL preceded radiation by 24 h. The enhancement factor derived from radiation dose-response curves was as high as 5.13. The radiosensitizing effect of PG-TXL was also dependent on the interval between PG-TXL administration and radiation delivery, with greater enhancement been observed when the interval was decreased. The percentage of G2/M cells was significantly increased to 21.4% 48 h after PG-TXL but declined to a preinjection level of 14.8% 72 h after PG-TXL. PG-TXL only moderately increased the tumor vascular volume by 37% 24 h after PG-TXL administration. Conclusion: PG-TXL markedly potentiated response of OCa-1 tumor to radiation. When compared to literature data obtained from the same tumor model used here, PG-TXL exhibited stronger radiosensitization effect than TXL. Although its

Data on genome analysis of Bacillus velezensis LS69

Directory of Open Access Journals (Sweden)

Guoqiang Liu

2017-08-01

Full Text Available The data presented in this article are related to the published entitled “Whole-genome sequencing of Bacillus velezensis LS69, a strain with a broad inhibitory spectrum against pathogenic bacteria” (Liu et al., 2017 [1]. Genome analysis revealed B. velezensis LS69 has a good potential for biocontrol and plant growth promotion. This article provides an extended analysis of the genetic islands, core genes and amylolysin loci of B. velezensis LS69.

Antitumor effect of iRGD-modified liposomes containing conjugated linoleic acid–paclitaxel (CLA-PTX on B16-F10 melanoma

Directory of Open Access Journals (Sweden)

Du R

2014-06-01

Full Text Available Ruo Du,1 Ting Zhong,1 Wei-Qiang Zhang,1 Ping Song,1 Wen-Ding Song,1 Yang Zhao,1 Chao-Wang,1 Yi-Qun Tang,3 Xuan Zhang,1,2 Qiang Zhang1,2 1Department of Pharmaceutics, 2State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 3Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC-modified sterically stabilized liposomes (SSLs containing conjugated linoleic acid–paclitaxel (CLA-PTX. The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy- and lipid raft-mediated endocytosis played a key role in the liposomes’ cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84±0.17 µg/g and 4 hours (1.17±0

Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

Science.gov (United States)

Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

2017-01-01

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

ASTROPHYSICAL PARAMETERS OF LS 2883 AND IMPLICATIONS FOR THE PSR B1259-63 GAMMA-RAY BINARY

International Nuclear Information System (INIS)

Negueruela, Ignacio; Lorenzo, Javier; Ribo, Marc; Herrero, Artemio; Khangulyan, Dmitry; Aharonian, Felix A.

2011-01-01

Only a few binary systems with compact objects display TeV emission. The physical properties of the companion stars represent basic input for understanding the physical mechanisms behind the particle acceleration, emission, and absorption processes in these so-called gamma-ray binaries. Here we present high-resolution and high signal-to-noise optical spectra of LS 2883, the Be star forming a gamma-ray binary with the young non-accreting pulsar PSR B1259-63, showing it to rotate faster and be significantly earlier and more luminous than previously thought. Analysis of the interstellar lines suggests that the system is located at the same distance as (and thus is likely a member of) Cen OB1. Taking the distance to the association, d = 2.3 kpc, and a color excess of E(B - V) = 0.85 for LS 2883 results in M V ∼ -4.4. Because of fast rotation, LS 2883 is oblate (R eq ≅ 9.7 R sun and R pole ≅ 8.1 R sun ) and presents a temperature gradient (T eq ∼ 27,500 K, log g eq = 3.7; T pole ∼ 34,000 K, log g pole = 4.1). If the star did not rotate, it would have parameters corresponding to a late O-type star. We estimate its luminosity at log(L * /L sun ) ≅ 4.79 and its mass at M * ∼ 30 M sun . The mass function then implies an inclination of the binary system i orb ∼ 23 0 , slightly smaller than previous estimates. We discuss the implications of these new astrophysical parameters of LS 2883 for the production of high-energy and very high-energy gamma rays in the PSR B1259-63/LS 2883 gamma-ray binary system. In particular, the stellar properties are very important for prediction of the line-like bulk Comptonization component from the unshocked ultrarelativistic pulsar wind.

Photoinduced membrane damage of E. coli and S. aureus by the photosensitizer-antimicrobial peptide conjugate eosin-(KLAKLAK2.

Directory of Open Access Journals (Sweden)

Gregory A Johnson

Full Text Available BACKGROUND/OBJECTIVES: Upon irradiation with visible light, the photosensitizer-peptide conjugate eosin-(KLAKLAK2 kills a broad spectrum of bacteria without damaging human cells. Eosin-(KLAKLAK2 therefore represents an interesting lead compound for the treatment of local infection by photodynamic bacterial inactivation. The mechanisms of cellular killing by eosin-(KLAKLAK2, however, remain unclear and this lack of knowledge hampers the development of optimized therapeutic agents. Herein, we investigate the localization of eosin-(KLAKLAK2 in bacteria prior to light treatment and examine the molecular basis for the photodynamic activity of this conjugate. METHODOLOGY/PRINCIPAL FINDINGS: By employing photooxidation of 3,3-diaminobenzidine (DAB, (scanning transmission electron microscopy ((STEM, and energy dispersive X-ray spectroscopy (EDS methodologies, eosin-(KLAKLAK2 is visualized at the surface of E. coli and S. aureus prior to photodynamic irradiation. Subsequent irradiation leads to severe membrane damage. Consistent with these observations, eosin-(KLAKLAK2 binds to liposomes of bacterial lipid composition and causes liposomal leakage upon irradiation. The eosin moiety of the conjugate mediates bacterial killing and lipid bilayer leakage by generating the reactive oxygen species singlet oxygen and superoxide. In contrast, the (KLAKLAK2 moiety targets the photosensitizer to bacterial lipid bilayers. In addition, while (KLAKLAK2 does not disrupt intact liposomes, the peptide accelerates the leakage of photo-oxidized liposomes. CONCLUSIONS/SIGNIFICANCE: Together, our results suggest that (KLAKLAK2 promotes the binding of eosin Y to bacteria cell walls and lipid bilayers. Subsequent light irradiation results in membrane damage from the production of both Type I & II photodynamic products. Membrane damage by oxidation is then further aggravated by the (KLAKLAK2 moiety and membrane lysis is accelerated by the peptide. These results therefore

125I Radioimmunoassay of serum ursodeoxycholyl conjugates

International Nuclear Information System (INIS)

Hill, A.; Ross, P.E.; Bouchier, I.A.D.

1983-01-01

A radioimmunoassay for serum ursodeoxycholic conjugates using an iodine-125 ligand has been developed. The bile acid was present in normal fasting serum (0.19 +- SD 0.19 μmol/l, n=24) and 2-hour post-prandial serum (0.8 +- SD 0.8 μmol/l, n=16). Gallstone patients undergoing oral ursodeoxycholic acid therapy had significantly higher post-prandial serum levels (21.5 +- SD 14.0 μmol/l, n=15) by radioimmunoassay. Gas liquid chromatography analysis indicated that in normal serum ursodeoxycholic acid was totally conjugated, whereas sera from gallstone patients contained a proportion as the free bile acid (10.2 +- SD 8.1 μmol/l, n=15). Following an oral dose of ursodeoxycholic acid, both unconjugated and conjugated forms of the bile acid appeared in the serum of healthy individuals. (Auth.)

Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

Energy Technology Data Exchange (ETDEWEB)

Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

2012-06-15

Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

The effect of liposome encapsulation on the pharmacokinetics of recombinant secretory leukocyte protease inhibitor (rSLPI) therapy after local delivery to a guinea pig asthma model.

LENUS (Irish Health Repository)

Gibbons, Aileen

2011-09-01

Inhaled recombinant Secretory Leukocyte Protease Inhibitor (rSLPI) has shown potential for treatment of inflammatory lung conditions. Rapid inactivation of rSLPI by cathepsin L (Cat L) and rapid clearance from the lungs have limited clinical efficacy. Encapsulation of rSLPI within 1,2-Dioleoyl-sn-Glycero-3-[Phospho-L-Serine]:Cholesterol liposomes (DOPS-rSLPI) protects rSLPI against Cat L inactivation in vitro. We aimed to determine the effect of liposomes on rSLPI pharmacokinetics and activity in vitro and after local delivery to the airways in vivo.

Radioprotective effectiveness of Adeturone incapsulated in liposomes

International Nuclear Information System (INIS)

Pantev, T.

1989-01-01

The radioprotective properties of the radioprotector Adeturone incapsulated in mono- and tricomponent liposomes were studied. Intraperitoneal administration of the radioprotector by means of monocomponent liposomes from egg lecithin, as well as its applicaton alone immediately (15-30 min) before irradiation of mice with 7,5 Gy gamma-quanta (LD 100/30 ) guaranteed high survival -80% and 75% accordingly. Orally introduced Adeturone, incapsulated in tricomponent liposomes (dipalmitoil lecithin, cholesterol, stearinamine - 7:2:1), protected for 0,5 to 4,5 hours lethally X-irradiated mice (7,8 Gy; LD 90/30 ). Under these conditions, Adeturone applied alone 4,5 hours before irradiation was ineffective. These results show the presence of prolonged radioprotective effect of Adeturone, when orally applied in the form of liposomal suspension. 2 tabs., 17 refs

Antibacterial activity of contact lenses bearing surface-immobilized layers of intact liposomes loaded with levofloxacin.

Science.gov (United States)

Danion, Anne; Arsenault, Isabelle; Vermette, Patrick

2007-09-01

In vitro methods to evaluate antibacterial activity were used with contact lenses bearing levofloxacin-loaded liposomes developed for the prevention and treatment of bacterial ocular infections such as keratitis. Levofloxacin was incorporated into liposomes before these intact liposomes were immobilized onto the surfaces of soft contact lenses using a multilayer immobilization strategy. The release of levofloxacin from contact lenses bearing 2, 5, and 10 layers of liposomes into a saline buffer at 37 degrees C was monitored by fluorescence. The levofloxacin release, as a function of time, was described by a mechanism taking into account two independent first-order kinetic models. The total release of levofloxacin from the contact lenses was completed within 6 days. The release of levofloxacin from contact lenses bearing 10 layers of liposomes and subsequently soaked overnight in a levofloxacin solution was also studied and compare to that of dried contact lenses without any chemical modification rehydrated in a levofloxacin solution. The antibacterial activity of the liposome-coated contact lenses against Staphylococcus aureus was evaluated by measuring (i) the diameters of the inhibition zone on an agar plate and (ii) the optical density using a broth assay. The liposome-coated lenses showed an antibacterial activity both on agar and in broth following 24 h. When initial bacteria inocula were equal or below 10(6) CFU/mL, all the bacteria were inhibited within 2 h. When using initial bacteria inocula of 10(8) CFU/mL, an initial burst release provided by soaking the liposomal lenses was required for the first hours to inhibit bacteria growth. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Physicochemical aspects of the liposome-wool interaction in wool dyeing.

Science.gov (United States)

Martí, Meritxell; Barsukov, Leonid I; Fonollosa, Jordi; Parra, José Luis; Sukhanov, Stanislav V; Coderch, Luisa

2004-04-13

Despite the promising application of liposomes in wool dyeing, little is known about the mechanism of liposome interactions with the wool fiber and dyestuffs. The kinetics of wool dyeing by two dyes, Acid Green 27 (hydrophobic) and Acid Green 25 (hydrophilic), were compared in three experimental protocols: (1) without liposomes, (2) in the presence of phosphatidylcholine (PC) liposomes, and (3) with wool previously treated with PC liposomes. Physicochemical interactions of liposomes with wool fibers were studied under experimental dyeing conditions with particular interest in the liposome affinity to the fiber surface and changes in the lipid composition of the wool fibers. The results obtained indicate that the presence of liposomes favors the retention of these two dyes in the dyeing bath, this effect being more pronounced in case of the hydrophobic dye. Furthermore, the liposome treatment is accompanied by substantial absorption of PC by wool fibers with simultaneous partial solubilization of their polar lipids (more evident at higher temperatures). This may result in structural modification of the cell membrane complex of wool fibers, which could account for a high level of the dye exhaustion observed at the end of the liposome dyeing process.

FT-IR, FT-Raman, NMR studies and ab initio-HF, DFT-B3LYP vibrational analysis of 4-chloro-2-fluoroaniline.

Science.gov (United States)

Arivazhagan, M; Anitha Rexalin, D

2012-10-01

The Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectra of 4-chloro-2-fluoroaniline (CFA) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational frequencies have been investigated with the help of ab initio and density functional theory (DFT) methods. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the Gauge including atomic orbital (GIAO) method. The first order hyperpolarizability (β(0)) of this novel molecular system and related properties (β, α(0) and Δα) of CFA are calculated using B3LYP/6-311++G(d,p) and HF/6-311++G(d,p) methods on the finite-field approach. The calculated results also show that the CFA molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The result confirms the occurrence of intramolecular charge transfer (ICT) within the molecule. The HOMO-LUMO energies UV-vis spectral analysis and MEP are performed by B3LYP/6-311++G(d,p) approach. A detailed interpretation of the infrared and Raman spectra of CFA is also reported based on total energy distribution (TED). The difference between the observed and scaled wave number values of the most of the fundamentals is very small. Copyright © 2012 Elsevier B.V. All rights reserved.

Diagnosis of leg osseous infection in diabetics: place of scintigraphy of the polynuclear hydrocarbons labelled by HMPAO-{sup 99m}Tc (HMPAO-LS); Diagnostic de l`infection osseuse du pied chez le diabetique: place de la scintigraphie aux polynucleaires marques a l`HMPAO-Tc 99m (HMPAO-LS)

Energy Technology Data Exchange (ETDEWEB)

Devillers, A.; Moisan, A.; Hennion, F.; Poirier, J.Y.; Bourguet, P. [CRLCC Eugene Marquis, Medecine Nucleaire, CHRU Endocrinologie, Rennes (France)

1997-12-31

In case of leg infection in diabetics it is difficult to differentiate between a chronic osteopathy, an infection of the soft tissues and an osteomyelitis (OM). We considered of interest to evaluate by a HMPAO-LS prospective study the diagnosis of osteitis in diabetic legs. Twenty seven diabetic (DID type 1 = 11, DNID type 2 = 16) patients (19 M and 8 F, average age 64 years), clinically suspected with a leg osteo-articular infection (malum perforans or cellulitis, uni- or bi-lateral, unique or multiple lesions) were included in the study. For all of them a standard radiographic examination centered on the legs, a (3 phases) osseous scintigraphy and a HMPAO-LS were achieved over 3 days. The HMPAO-LS was considered as in favour of a OM when there was an abnormal accumulation of granulocytes concordant with a hyper-fixation by osseous scintigraphy. In case of 37 retained lesions 20 OM were proved: - 8 sites, on radiological arguments and histological and/or microbiological criteria after osseous biopsy; - 8, by the radiological examination only; - 4, on biopsy arguments, only. Seventeen lesions were not OM, of which 7 were cellulitis. The sensitivity of the HMPAO-LS was 90% with a specificity of 94%. 8/20 OM had initial normal radiographs confirming the precocity of OM diagnosis by HMPAO-LS. Twelve HMPAO-LS were effected in OM evolutive surveillance. All of them became negative on the control initial site of the healing of OM. In conclusion, the HMPAO-LS appears to be an alternative to choose in the diagnosis and in the evolution surveillance of leg OM in diabetics, particularly when the healing of the perforans softs is incomplete and the question of the osteitis healing or sequel of an anti-biotherapy is posed

Forsskåls Fiskeherbarium

DEFF Research Database (Denmark)

Provencal, Philippe

2017-01-01

En beskrivelse af Peter Forsskåls fiskeherbarium og hans metoder i det marinbiologiske feltarbejde da han rejste i Egypten, Rødehavet og Yemen som ekspeditionsmedlem i den Arabiske Rejse 2061-67.......En beskrivelse af Peter Forsskåls fiskeherbarium og hans metoder i det marinbiologiske feltarbejde da han rejste i Egypten, Rødehavet og Yemen som ekspeditionsmedlem i den Arabiske Rejse 2061-67....

Targeted drug delivery using temperature-sensitive liposomes

International Nuclear Information System (INIS)

Magin, R.L.; Niesman, M.R.

1984-01-01

Liposomes are receiving considerable attention as vehicles for selective drug delivery. One method of targeting liposomal contents involves the combination of local hyperthermia with temperature-sensitive liposomes. Such liposomes have been used to increase the uptake of methotrexate and cis-platinum into locally heated mouse tumors. However, additional information is needed on the mechanism of liposome drug release and the physiologic deposition of liposomes in vivo before clinical trails are begun. Current research is directed at studying the encapsulation and release of water soluble drugs from temperature-sensitive liposomes. The influence of liposome size, structure, and composition on the rapid release in plasma of cytosine arabinoside, cis-platinum, and the radiation sensitizer SR-2508 are described. These results demonstrate potential applications for temperature-sensitive liposomes in selective drug delivery

Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes.

Directory of Open Access Journals (Sweden)

Valentina Perri

Full Text Available Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target. We aimed to develop novel wild type PTPN22 short interfering RNA duplexes (siRNA and optimize their delivery into Jurkat T cells and PBMC by using liposomal carriers. Conformational stability, size and polydispersion of siRNA in lipoplexes was measured by CD spectroscopy and DLS. Lipoplexes internalization and toxicity evaluation was assessed by confocal microscopy and flow cytometry analysis. Their effect on Lyp expression was evaluated by means of Western Blot and confocal microscopy. Functional assays through engagement of TCR signaling were established to evaluate biological consequences of down-modulation. Both Jurkat T cells and PBMC were efficiently transfected by stable custom lipoplexes. Jurkat T cell morphology and proliferation was not affected. Lipoplexes incorporation was visualized in CD3+ but also in CD3- peripheral blood immunotypes without signs of toxicity, damage or apoptosis. Efficacy in affecting Lyp protein expression was demonstrated in both transfected Jurkat T cells and PBMC. Moreover, impairment of Lyp inhibitory activity was revealed by increase of IL-2 secretion in culture supernatants of PBMC following anti-CD3/CD28 T cell receptor-driven stimulation. The results of our study open the pathway to future trials for the treatment of autoimmune diseases based

Comparison of linoleic and conjugated linoleic acids in enzymatic acidolysis of tristearin

DEFF Research Database (Denmark)

Yang, Tiankui; Xu, Xuebing; Li, L.T.

2001-01-01

tristearin (SSS) and linoleic (L) or conjugated linoleic (cL) acids (1:6, mol/mol). The other was between tristearin and the mixture of linoleic and conjugated linoleic acids (1:3:3, mol/mol/mol). Acyl incorporation and migration together with triacylglycerol composition of the products were monitored...... with gas chromatography, pancreatic lipase hydrolysis, and high performance liquid chromatography. Both acyl incorporation and migration of linoleic acid were faster than those of conjugated linoleic acid. At 5 h reaction, there were 13.0% LLL, 46.5% LSL, 27.7% LSS, and 5.6% SSS in the product for a system...... between tristearin and linoleic acid; whereas there were 2.4% cLcLcL, 10.4% cLScL, 50.9% cLSS, and 36.2% SSS in the product for a system between tristearin and conjugated linoleic acid. The results suggest that linoleic acid was more reactive than conjugated linoleic acid in the enzymatic acidolysis...

/sup 125/I Radioimmunoassay of serum ursodeoxycholyl conjugates

Energy Technology Data Exchange (ETDEWEB)

Hill, A.; Ross, P.E.; Bouchier, I.A.D. (Ninewells Hospital and Medical School, Dundee (UK))

1983-02-07

A radioimmunoassay for serum ursodeoxycholic conjugates using an iodine-125 ligand has been developed. The bile acid was present in normal fasting serum (0.19 +- SD 0.19 ..mu..mol/l, n=24) and 2-hour post-prandial serum (0.8 +- SD 0.8 ..mu..mol/l, n=16). Gallstone patients undergoing oral ursodeoxycholic acid therapy had significantly higher post-prandial serum levels (21.5 +- SD 14.0 ..mu..mol/l, n=15) by radioimmunoassay. Gas liquid chromatography analysis indicated that in normal serum ursodeoxycholic acid was totally conjugated, whereas sera from gallstone patients contained a proportion as the free bile acid (10.2 +- SD 8.1 ..mu..mol/l, n=15). Following an oral dose of ursodeoxycholic acid, both unconjugated and conjugated forms of the bile acid appeared in the serum of healthy individuals.

Intestinal APCs of the endogenous nanomineral pathway fail to express PD-L1 in Crohn’s disease

Science.gov (United States)

Robertson, Jack; Haas, Carolin T.; Pele, Laetitia C.; Monie, Tom P.; Charalambos, Charles; Parkes, Miles; Hewitt, Rachel E.; Powell, Jonathan J.

2016-01-01

Crohn’s disease is a chronic inflammatory condition most commonly affecting the ileum and colon. The aetiology of Crohn’s disease is complex and may include defects in peptidoglycan recognition, and/or failures in the establishment of intestinal tolerance. We have recently described a novel constitutive endogenous delivery system for the translocation of nanomineral-antigen-peptidoglycan (NAP) conjugates to antigen presenting cells (APCs) in intestinal lymphoid patches. In mice NAP conjugate delivery to APCs results in high surface expression of the immuno-modulatory molecule programmed death receptor ligand 1 (PD-L1). Here we report that NAP conjugate positive APCs in human ileal tissues from individuals with ulcerative colitis and intestinal carcinomas, also have high expression of PD-L1. However, NAP-conjugate positive APCs in intestinal tissue from patients with Crohn’s disease show selective failure in PD-L1 expression. Therefore, in Crohn’s disease intestinal antigen taken up by lymphoid patch APCs will be presented without PD-L1 induced tolerogenic signalling, perhaps initiating disease. PMID:27226337

Methylation of the phosphate oxygen moiety of phospholipid-methoxy(polyethylene glycol) conjugate prevents PEGylated liposome-mediated complement activation and anaphylatoxin production

DEFF Research Database (Denmark)

Moghimi, S.M.; Hamad, I.; Andresen, Thomas Lars

2006-01-01

Methoxy(polyethylene glycol), mPEG, -grafted liposomes are known to exhibit prolonged circulation time in the blood, but their infusion into a substantial percentage of human subjects triggers immediate non-IgE-mediated hypersensitivity reactions. These reactions are strongly believed to arise from...... to PEGylated liposome-mediated complement activation. Our findings provide a rational conceptual basis for development of safer vesicles for site-specific drug delivery and controlled release at pathological sites....

Physico-chemical studies on the interaction of dendrimers with lipid bilayers. 1. Effect of dendrimer generation and liposome surface charge.

Science.gov (United States)

Roy, Biplab; Panda, Amiya Kumar; Parimi, Srinivas; Ametov, Igor; Barnes, Timothy; Prestidge, Clive A

2014-01-01

Studies on the interaction of different generation poly (amido amine) (PAMAM) dendrimers (2G, 4G and 6G) and liposomes of different compositions were carried out by a combined turbidity, dynamic light scattering and atomic force microscopic measurements. Liposomes comprising soy lecithin (SLC, negative surface charge), 1, 2-palmitoyl-sn-glycero-3-phosphatidylcholine (DPPC, mildly positive surface charge), 1,2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol (DPPG, negatively charged) and a biologically simulated mixture of DPPC + DPPG (7:3, M/M, negatively charged) were used as model bilayers. 30 wt% cholesterol was used in each combination as it is known to control the fluidity of membrane bilayers. Silica was used as a negatively charged hard sphere model with an aim to compare the results. Both the turbidity and hydrodynamic diameter values of all the liposomes, except DPPC, passed through maxima upon the progressive addition of PAMAM; the effect was insignificant in case of DPPC. Formation of dendriosome, a complex formed between dendrimer and liposome, resulted in the charge reversal of the negatively charged liposomes. Interaction between PAMAM and liposome was found to be governed by electrostatic as well as hydrogen bonding. Generation dependent PAMAM activity followed the order: 6G >4G>2G in terms of overall dendrimer concentration. However, interestingly, the order was reverse when PAMAM activity was considered in terms of total end group concentrations. AFM studies reveal the rupture of bilayer structure upon addition of dendrimer.

Optimization and characterization of liposome formulation by mixture design.

Science.gov (United States)

Maherani, Behnoush; Arab-tehrany, Elmira; Kheirolomoom, Azadeh; Reshetov, Vadzim; Stebe, Marie José; Linder, Michel

2012-02-07

This study presents the application of the mixture design technique to develop an optimal liposome formulation by using the different lipids in type and percentage (DOPC, POPC and DPPC) in liposome composition. Ten lipid mixtures were generated by the simplex-centroid design technique and liposomes were prepared by the extrusion method. Liposomes were characterized with respect to size, phase transition temperature, ζ-potential, lamellarity, fluidity and efficiency in loading calcein. The results were then applied to estimate the coefficients of mixture design model and to find the optimal lipid composition with improved entrapment efficiency, size, transition temperature, fluidity and ζ-potential of liposomes. The response optimization of experiments was the liposome formulation with DOPC: 46%, POPC: 12% and DPPC: 42%. The optimal liposome formulation had an average diameter of 127.5 nm, a phase-transition temperature of 11.43 °C, a ζ-potential of -7.24 mV, fluidity (1/P)(TMA-DPH)((¬)) value of 2.87 and an encapsulation efficiency of 20.24%. The experimental results of characterization of optimal liposome formulation were in good agreement with those predicted by the mixture design technique.

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design.

Science.gov (United States)

Pujade-Lauraine, Eric; Fujiwara, Keiichi; Dychter, Samuel S; Devgan, Geeta; Monk, Bradley J

2018-03-27

Avelumab is a human anti-PD-L1 checkpoint inhibitor with clinical activity in multiple solid tumors. Here, we describe the rationale and design for JAVELIN Ovarian 200 (NCT02580058), the first randomized Phase III trial to evaluate the role of checkpoint inhibition in women with ovarian cancer. This three-arm trial is comparing avelumab administered alone or in combination with pegylated liposomal doxorubicin versus pegylated liposomal doxorubicin alone in patients with platinum-resistant/refractory recurrent ovarian, fallopian tube or peritoneal cancer. Eligible patients are not preselected based on PD-L1 expression and may have received up to three prior lines of chemotherapy for platinum-sensitive disease, but none for resistant disease. Overall survival and progression-free survival are primary end points, and secondary end points include biomarker evaluations and pharmacokinetics.

Liposomes as carriers of imaging agents

International Nuclear Information System (INIS)

Caride, V.J.

1985-01-01

This review discusses the utilization of liposomes as imaging agents or as vehicles for contrast materials. The initial approach was the use of radiolabeled liposomes for scintigraphy. To this end liposomes were either labeled in the lipid membrane or aqueous radiotracers were incorporated inside the lipid vesicles. The lipid labeling provides a more stable association of the radioactive tracer and the lipid vesicles, while the use of water-soluble radiotracers provides a wider selection of compounds. Early attempts at selective tumor imaging using radiolabeled liposomes were unsuccessful. The use of monoclonal antibodies attached to liposomes offers new hopes. Several strategies have been proposed in this respect and several others can be envisioned. The use of liposomes permits the use of several administration routes for imaging agents. Of particular interest is the subcutaneous administration for lymph node visualization. Liposomes offer clear advantages over most radiocontrast agents for prolonged hepatosplenic contrast enhancement. This is particularly relevant in the diagnostic evaluation of the abdomen with computed tomography. Important research efforts are being conducted in this area. Two different approaches have been advanced: the incorporation of contrast agents into liposomes and the preparation of radiopaque liposomes from radiodense lipids. Nuclear magnetic resonance imaging can also benefit from contrast agents. Several centers are investigating this exciting field using liposomes loaded with paramagnetic elements.152 references

Propulsion of liposomes using bacterial motors

International Nuclear Information System (INIS)

Zhang Zhenhai; Li Kejie; Li Zhifei; Yu Wei; Xie Zhihong; Shi Zhiguo

2013-01-01

Here we describe the utilization of flagellated bacteria as actuators to propel spherical liposomes by attaching bacteria to the liposome surface. Bacteria were stably attached to liposomes using a cross-linking antibody. The effect of the number of attached bacteria on propulsion speed was experimentally determined. The effects of bacterial propulsion on the bacteria–antibody–liposome complex were stochastic. We demonstrated that liposomal mobility increased when bacteria were attached, and the propulsion speed correlated with the number of bacteria. (paper)

Accurate Energies and Structures for Large Water Clusters Using the X3LYP Hybrid Density Functional

OpenAIRE

Su, Julius T.; Xu, Xin; Goddard, William A., III

2004-01-01

We predict structures and energies of water clusters containing up to 19 waters with X3LYP, an extended hybrid density functional designed to describe noncovalently bound systems as accurately as covalent systems. Our work establishes X3LYP as the most practical ab initio method today for calculating accurate water cluster structures and energies. We compare X3LYP/aug-cc-pVTZ energies to the most accurate theoretical values available (n = 2−6, 8), MP2 with basis set superposition error (BSSE)...

Amperometric glucose biosensor based on layer-by-layer films of microperoxidase-11 and liposome-encapsulated glucose oxidase.

Science.gov (United States)

Graça, J S; de Oliveira, R F; de Moraes, M L; Ferreira, M

2014-04-01

An important step in several bioanalytical applications is the immobilization of biomolecules. Accordingly, this procedure must be carefully chosen to preserve their biological structure and fully explore their properties. For this purpose, we combined the versatility of the layer-by-layer (LbL) method for the immobilization of biomolecules with the protective behavior of liposome-encapsulated systems to fabricate a novel amperometric glucose biosensor. To obtain the biosensing unit, an LbL film of the H2O2 catalyst polypeptide microperoxidase-11 (MP-11) was assembled onto an indium-tin oxide (ITO) electrode followed by the deposition of a liposome-encapsulated glucose oxidase (GOx) layer. The biosensor response toward glucose detection showed a sensitivity of 0.91±0.09 (μA/cm2)/mM and a limit of detection (LOD) of 8.6±1.1 μM, demonstrating an improved performance compared to similar biosensors with a single phospholipid-liposome or even containing a non-encapsulated GOx layer. Finally, glucose detection was also performed in a zero-lactose milk sample to demonstrate the potential of the biosensor for food analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Purification and genetic characterisation of the novel bacteriocin LS2 produced by the human oral strain Lactobacillus salivarius BGHO1.

Science.gov (United States)

Busarcevic, Milos; Dalgalarrondo, Michèle

2012-08-01

The aim of this study was to investigate the antimicrobial potential of Lactobacillus salivarius BGHO1, a human oral strain with probiotic characteristics and a broad inhibitory spectrum both against Gram-positive and Gram-negative pathogens. Here we present the bacteriocin LS2, an extremely pH- and heat-stable peptide with antilisterial activity. LS2 is a novel member of the class IId bacteriocins, unique among all currently characterised bacteriocins. It is somewhat similar to putative bacteriocins from several oral streptococci, including the cariogenic Streptococcus mutans. LS2 is a 41-amino-acid, highly hydrophobic cationic peptide of 4115.1Da that is sensitive to proteolytic enzymes. LS2 was purified from cells of strain BGHO1 by solvent extraction and reverse-phase chromatography. Mass spectrometry was used to determine the molecular mass of the purified peptide. N-terminal amino acid sequencing enabled identification of the LS2 structural gene bacls2 by a reverse genetics approach. Downstream of the bacls2 gene, two bacteriocin-like genes were found, named blp1a and blp1b, and one putative bacteriocin immunity gene named bimlp. We also present the identification of the 242-kb megaplasmid pMPHO1 by pulsed-field gel electrophoresis, which harbours the genes bacls2, blp1a, blp1b and bimlp. Two peptides with antimicrobial activity, whose approximate sizes corresponded to those of blp1a and blp1b, were identified only after culturing strain BGHO1 in a chemically defined medium. This study demonstrated the capacity of Lactobacillus salivarius BGHO1 to produce multiple bacteriocins and further established this strain as a promising probiotic candidate. Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration.

Science.gov (United States)

Franzé, Silvia; Marengo, Alessandro; Stella, Barbara; Minghetti, Paola; Arpicco, Silvia; Cilurzo, Francesco

2018-01-15

The work aimed to evaluate the feasibility to design hyaluronic acid (HA) decorated flexible liposomes to enhance the skin penetration of nifedipine. Egg phosphatidylcholine (e-PC) based transfersomes (Tween 80) and transethosomes (ethanol) were prepared. HA was reacted with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (HA-DPPE) and two molar ratios (0.5 and 3%) of conjugate with respect to e-PC were tested. The presence of HA significantly increased the packing order of the bilayer (as verified by differential scanning calorimetry), reducing both the encapsulation efficiency and the flexibility of the decorated liposomes in a dose-dependent manner. In fact, at the highest HA content the constant of deformability (K, N/mm) increased and the carriers remained on the skin surface after topical application. The stiffening effect of HA was counterbalanced by the addition of ethanol as fluidizing agent that allowed to maintain the highest HA concentration, meanwhile reducing the K value of the vesicles. HA-transethosomes allowed a suitable nifedipine permeation (J ∼ 30 ng/cm 2 /h) and significantly improved the drug penetration, favouring the formation of a drug depot in the epidermis. These data suggest the potentialities of HA-transethosomes as drug delivery systems intended for the treatment of cutaneous pathologies and underline the importance of studying the effect of surface functionalization on carrier deformability to rationalize the design of such systems. Copyright © 2017 Elsevier B.V. All rights reserved.

LS1 Report: Setting the bar high

CERN Multimedia

Anaïs Schaeffer

2014-01-01

This week LS1 successfully passed an important milestone: the first pressure test of a complete sector, sector 6-7.  The objective of this test was to check the mechanical integrity and overall leak-tightness of this section of the LHC by injecting it with pressurised helium.   The team in charge of the preparation and of the realisation of the pressure tests in sector 6-7. “Given the scale of the work and of the operations carried out during 2013, particularly in the framework of the SMACC project and of the repair of the compensators of the cryogenic distribution line (QRL), we need to revalidate the integrity of the systems before the accelerator starts up again,” explains Olivier Pirotte, who is in charge of the pressure tests (TE-CRG). The pressure tests are performed over a single day after two weeks of intensive activity to prepare and specially configure the cryogenic instrumentation in the tunnel, and the pressure within a sector is increased in stages,...

LS1 Report: Thank you magnetic horn!

CERN Multimedia

Antonella Del Rosso & Katarina Anthony

2014-01-01

Experiments at the Antimatter Decelerator (AD) have been receiving beams since the beginning of this week. There is a crucial element at the heart of the chain that prepares the antiproton beam: the so-called magnetic horn, a delicate piece of equipment that had to be refurbished during LS1 and that is now showing just how well it can perform.   View from the top of the target and horn trolley, along the direction of the beam. Antiprotons for the AD are produced by smashing a beam of protons from the PS onto an iridium target. However, the particles produced by the nuclear interactions are emitted at very wide angles; without a focussing element, all these precious particles would be lost. “A magnetic horn is placed at the exit of the target to focus back a large fraction of the negative particles, including antiprotons, parallel to the beam line and with the right momentum,” explains Marco Calviani, physicist in the EN Department and the expert in charge of the AD targe...

LS1 Report: ALICE ups the ante

CERN Multimedia

Katarina Anthony

2014-01-01

SPS up and running... LHC almost cold... CCC Operators back at their desks... all telltale signs of the start of Run 2! For the experiments, that means there are just a few short months left for them to prepare for beams. The CERN Bulletin will be checking in with each of the Big Four to see how they are getting on during these closing months...   It has been a long road for the ALICE LS1 team. From major improvements to the 19 sub-detectors to a full re-cabling and replacement of LEP-era electrical infrastructure, no part of the ALICE cavern has gone untouched.* With the experiment set to close in early December, the teams are making finishing touches before turning their focus towards re-commissioning and calibration. "Earlier this week, we installed the last two modules of the di-jet calorimeter," explains Werner Riegler, ALICE technical coordinator. "These are the final parts of a 60 degree calorimeter extension that is installed opposite the present calorimeter, c...

Controlling a Conventional LS-pump based on Electrically Measured LS-pressure

DEFF Research Database (Denmark)

Pedersen, Henrik Clemmensen; Andersen, Torben Ole; Hansen, Michael Rygaard

2008-01-01

As a result of the increasing use of sensors in mobile hydraulic equipment, the need for hydraulic pilot lines is decreasing, being replaced by electrical wiring and electrically controllable components. For controlling some of the existing hydraulic components there are, however, still a need...... this system, by either generating a copy of the LS-pressure, the LS-pressure being the output, or letting the output be the pump pressure. The focus of the current paper is on the controller design based on the first approach. Specifically a controlled leakage flow is used to avoid the need for a switching...

Nanoparticle Stabilized Liposomes for Acne Therapy

Science.gov (United States)

Fu, Victoria

Acne vulgaris is a common skin disease that affects over 40 million people in the United States alone. The main cause of acne vulgaris is Propionibacterium acnes (P. acnes), resides deep in the pores and follicles of the skin in order to feed on oil produced by the sebaceous glands. The liposome is a lipid based nanoparticle with numerous advantages over free drug molecules as an acne treatment alternative. Bare liposomes loaded with lauric acid (LipoLA) were found to show strong antimicrobial activity against P. acnes while generating minimal toxicity. However, the platform is limited by the spontaneous tendency of liposomes to fuse with each other. Attaching nanoparticles to the surface of liposomes can overcome this challenge by providing steric repulsion and reduce surface tension. Thus, carboxyl-functionalized gold nanoparticles (AuC) were attached to the surface of liposomes (AuC-liposomes) loaded with doxycycline, a general tetracycline antibiotic. These particles were found to have a diameter of 120 nm and a zeta potential of 20.0 mV. Both fluorescent and antimicrobial studies demonstrated that based on electrostatic interaction, negatively charged AuC attached to the liposome's positively charged surface and stabilized liposomes in a neutral pH environment (pH = 7.4). Upon entering the skin's acidic environment (pH = 4), AuC detached from the liposome's surface and liposomes could fuse with P. acnes residing in the pores. Furthermore, toxicity studies showed that AuC-liposomes did not induce any significant toxicity, while two of the leading over-the-counter therapies, benzoyl peroxide and salicylic acid, generated substantial skin irritation.

R2E strategy and activities during LS1

International Nuclear Information System (INIS)

Perrot, A.L.

2012-01-01

The level of the flux of hadrons with energy in the multi MeV range expected from the collimation system at Point 7 and from the collisions at the interaction Points 1, 5 and 8 will induce Single Event Errors (SEEs) of the standard electronics present in the equipment located around these Points. Such events would perturb LHC operation. As a consequence, within the framework of the R2E (Radiation to Electronics) Mitigation Project, the sensitive equipment will be shielded or relocated to safer areas. These mitigation activities will be performed mainly during Long Shutdown 1 (LS1). About 15 groups (including equipment owners) will be involved in these activities with work periods from a few days to several months. Some of them will have to work in parallel in several LHC points. This document presents these mitigation activities with their associated planning, organization process, and main concerns as identified today. (author)

Pain Reduction in Untreated Symptomatic Irreversible Pulpitis Using Liposomal Bupivacaine (Exparel): A Prospective, Randomized, Double-blind Trial.

Science.gov (United States)

Bultema, Kristy; Fowler, Sara; Drum, Melissa; Reader, Al; Nusstein, John; Beck, Mike

2016-12-01

In the treatment of patients with symptomatic irreversible pulpitis, endodontic debridement is a predictable method to relieve pain. However, there are clinical situations in which emergency care cannot be provided immediately. An unexplored treatment option in these cases may be the use of a long-acting anesthetic to reduce pain in untreated irreversible pulpitis. Some medical studies have shown potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA) to prolong pain relief and reduce opioid use postoperatively. The Food and Drug Administration has approved Exparel only for infiltrations; therefore, the purpose of this study was to compare an infiltration of liposomal bupivacaine versus bupivacaine for pain control in untreated, symptomatic irreversible pulpitis. Ninety-five emergency patients received 2% lidocaine with 1:100,000 epinephrine via infiltration or an inferior alveolar nerve block to relieve their initial presenting pain. Patients then randomly received either 4 mL liposomal bupivacaine (13.3 mg/mL) or 4 mL 0.5% bupivacaine with 1:200,000 epinephrine by infiltration. Patients received a diary for the day of the appointment and 3 days postinjection to record soft tissue numbness, pain levels, and analgesic (non-narcotic and narcotic) use. No significant differences (P pulpitis. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

In vivo and in vitro evaluation of octyl methoxycinnamate liposomes

Directory of Open Access Journals (Sweden)

de Carvalho Varjão Mota A

2013-12-01

Full Text Available Aline de Carvalho Varjão Mota,1 Zaida Maria Faria de Freitas,1 Eduardo Ricci Júnior,1 Gisela Maria Dellamora-Ortiz,1 Ralph Santos-Oliveira,2 Rafael Antonio Ozzetti,3 André Luiz Vergnanini,3 Vanessa Lira Ribeiro,4 Ronald Santos Silva,4 Elisabete Pereira dos Santos11Faculty of Pharmacy, Federal University of Rio de Janeiro, 2Nuclear Engineering Institute, National Nuclear Energy Commission, 3Allergisa Dermatocosmetic Research, University of Campinas, São Paulo, 4Pharmacology and Toxicology Department, National Insitute of Quality Control in Health, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilAbstract: Solar radiation causes damage to human skin, and photoprotection is the main way to prevent these harmful effects. The development of sunscreen formulations containing nanosystems is of great interest in the pharmaceutical and cosmetic industries because of the many potential benefits. This study aimed to develop and evaluate an octyl methoxycinnamate (OMC liposomal nanosystem (liposome/OMC to obtain a sunscreen formulation with improved safety and efficacy by retaining OMC for longer on the stratum corneum.Methods: The liposome/OMC nanostructure obtained was tested for enzymatic hydrolysis with lipase from Rhizomucor miehei and biodistribution with liposomes labeled with technetium-99m. The liposome/OMC formulation was then incorporated in a gel formulation and tested for ocular irritation using the hen’s egg test-chorio-allantoic membrane (HET-CAM assay, in vitro and in vivo sun protection factor, in vitro release profile, skin biometrics, and in vivo tape stripping.Results: The liposome/OMC nanosystem was not hydrolyzed from R. miehei by lipase. In the biodistribution assay, the liposome/OMC formulation labeled with technetium-99m had mainly deposited in the skin, while for OMC the main organ was the liver, showing that the liposome had higher affinity for the skin than OMC. The liposome/OMC formulation was classified as nonirritating in

Preparation of liposomal amiodarone and investigation of its cardiomyocyte-targeting ability in cardiac radiofrequency ablation rat model

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Zhuge Y

2016-05-01

Full Text Available Ying Zhuge,1,* Zhi-Feng Zheng,1,* Mu-Qing Xie,2 Lin Li,2 Fang Wang,1 Feng Gao2,3 1Department of Cardiology, Shanghai First People’s Hospital of Nanjing Medical University, 2Department of Pharmaceutics, School of Pharmacy, 3Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: The objective of this study was to develop an amiodarone hydrochloride (ADHC-loaded liposome (ADHC-L formulation and investigate its potential for cardiomyocyte targeting after cardiac radiofrequency ablation (CA in vivo. The ADHC-L was prepared by thin-film method combined with ultrasonication and extrusion. The preparation process was optimized by Box–Behnken design with encapsulation efficiency as the main evaluation index. The optimum formulation was quantitatively obtained with a diameter of 99.9±0.4 nm, a zeta potential of 35.1±10.9 mV, and an encapsulation efficiency of 99.5%±13.3%. Transmission electron microscopy showed that the liposomes were spherical particles with integrated bilayers and well dispersed with high colloidal stability. Pharmacokinetic studies were investigated in rats after intravenous administration, which revealed that compared with free ADHC treatment, ADHC-L treatment showed a 5.1-fold increase in the area under the plasma drug concentration–time curve over a period of 24 hours (AUC0–24 h and an 8.5-fold increase in mean residence time, suggesting that ADHC-L could facilitate drug release in a more stable and sustained manner while increasing the circulation time of ADHC, especially in the blood. Biodistribution studies of ADHC-L demonstrated that ADHC concentration in the heart was 4.1 times higher after ADHC-L treatment in CA rat model compared with ADHC-L sham-operated treatment at 20 minutes postinjection. Fluorescence imaging studies further proved that the heart

Development of a molecularly imprinted polymer tailored on disposable screen-printed electrodes for dual detection of EGFR and VEGF using nano-liposomal amplification strategy.

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Johari-Ahar, Mohammad; Karami, Pari; Ghanei, Mostafa; Afkhami, Abbas; Bagheri, Hasan

2018-06-01

This work demonstrates the development of a gold screen-printed electrode (Au-SPE)-based biosensor modified with a molecularly imprinted polymer and amplified using antibody-conjugated nano-liposomes. The developed biosensor was utilized for dual determination of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) as cancer biomarkers. To prepare this biosensor, Au-SPE was modified with 3,3'-dithiodipropionic acid di(N-hydroxysuccinimide ester) via self-assembly method and then the target proteins (EGFR and VEGF) were covalently attached to the modified SPE. To synthesize the molecularly imprinted polymer, monomers of acrylamide and N,N'-methylenebis(acrylamide) were polymerized around the EGFR and VEGF templates, and to characterize the prepared biosensor, electrochemical impedance spectroscopy was used for analyses of surface changes in the engineered electrodes. To produce reliable electrochemical signals, nano-liposomes which were loaded with Cd(II) and Cu(II) cations and decorated with antibodies specific for EGFR and VEGF were used as an efficient tool for detection of target biomarkers. In the analysis step, potentiometric striping analysis (PSA), as an electrochemical technique, was utilized for sensitive determination of these cations. The limits of detection (LODs) of EGFR and VEGF analyses were found to be 0.01 and 0.005 pg mL -1 with the linear dynamic ranges (LDRs) of 0.05-50000 and 0.01-7000 pg mL -1 , respectively. Moreover, the proposed biosensor was successfully used for sensitive, reproducible, and specific detection of EGFR and VEGF in real samples. Due to the SPE nature of the developed biosensor, we envision that this sensing tool has capability of being integrated with lab-on-a-chip (LOC), microfluidics, and micro total analysis systems. Copyright © 2018 Elsevier B.V. All rights reserved.

Internalization and Subcellular Trafficking of Poly-l-lysine Dendrimers Are Impacted by the Site of Fluorophore Conjugation.

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Avaritt, Brittany R; Swaan, Peter W

2015-06-01

Internalization and intracellular trafficking of dendrimer-drug conjugates play an important role in achieving successful drug delivery. In this study, we aimed to elucidate the endocytosis mechanisms and subcellular localization of poly-l-lysine (PLL) dendrimers in Caco-2 cells. We also investigated the impact of fluorophore conjugation on cytotoxicity, uptake, and transepithelial transport. Oregon green 514 (OG) was conjugated to PLL G3 at either the dendrimer periphery or the core. Chemical inhibitors of clathrin-, caveolin-, cholesterol-, and dynamin-mediated endocytosis pathways and macropinocytosis were employed to establish internalization mechanisms, while colocalization with subcellular markers was used to determine dendrimer trafficking. Cell viability, internalization, and uptake were all influenced by the site of fluorophore conjugation. Uptake was found to be highly dependent on cholesterol- and dynamin-mediated endocytosis as well as macropinocytosis. Dendrimers were trafficked to endosomes and lysosomes, and subcellular localization was impacted by the fluorophore conjugation site. The results of this study indicate that PLL dendrimers exploit multiple pathways for cellular entry, and internalization and trafficking can be impacted by conjugation. Therefore, design of dendrimer-drug conjugates requires careful consideration to achieve successful drug delivery.

Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A

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Leserman, Lee D.; Barbet, Jacques; Kourilsky, François; Weinstein, John N.

1980-12-01

Many applications envisioned for liposomes in cell biology and chemotherapy require their direction to specific cellular targets1-3. The ability to use antibody as a means of conferring specificity to liposomes would markedly increase their usefulness. We report here a method for covalently coupling soluble proteins, including monoclonal antibody and Staphylococcus aureus protein A (ref. 4), to small sonicated liposomes, by using the heterobifunctional cross-linking reagent N-hydroxysuccinimidyl 3-(2-pyridyldithio)propionate (SPDP, Pharmacia). Liposomes bearing covalently coupled mouse monoclonal antibody against human β2-microglobulin [antibody B1.1G6 (IgG2a, κ) (B. Malissen et al., in preparation)] bound specifically to human, but not to mouse cells. Liposomes bearing protein A became bound to human cells previously incubated with the B1.1G6 antibody, but not to cells incubated without antibody. The coupling method results in efficient binding of protein to the liposomes without aggregation and without denaturation of the coupled ligand; at least 60% of liposomes bound functional protein. Further, liposomes did not leak encapsulated carboxyfluorescein (CF) as a consequence of the reaction.

Inhibition of growth of human breast cancer cells in culture by neutron capture using liposomes containing 10B.

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Yanagië, H; Kobayashi, H; Takeda, Y; Yoshizaki, I; Nonaka, Y; Naka, S; Nojiri, A; Shinnkawa, H; Furuya, Y; Niwa, H; Ariki, K; Yasuhara, H; Eriguchi, M

2002-03-01

Cell destruction in boron neutron capture therapy is effected by nuclear reaction between 10B and thermal neutrons with the release of alpha-particles (4He) and lithium-7 ions (7Li). 4He kills cells within 10 microm of the site of 4He generation, therefore it is theoretically possible to destroy tumour cells without affecting adjacent healthy tissue, given selective delivery of compounds containing 10B. Liposomes wore prepared by vortex dispersion of solutions containing 10B compounds with dried lipid films and the effects of those compounds on human breast cancer cells in culture were examined after thermal neutral irradiation. [3H]-TdR incorporation by MRKnu/nu-1 cells treated with 10B-containing liposomes showed 40% suppression compared with liposomes without 10B, at 2 x 1012 n/cm2 thermal neutron fluence. Inhibition of tumour cell growth with liposomes prepared with 100 mm 10B-compound was as significant as with those made with 500 ppm 10B solution. The concentration of 10B in liposomes was 76.5 +/- 3.4 microg/mL. Boronated liposomes can thus deliver sufficient 10B atoms to this line of breast cancer cells in culture to effect cytotoxicity and suppression of growth after thermal neutron irradiation.

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

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Gradauer K

2012-05-01

Full Text Available Kerstin Gradauer,1 Caroline Vonach,1 Gerd Leitinger,2,3 Dagmar Kolb,2,3 Eleonore Fröhlich,3 Eva Roblegg,4 Andreas Bernkop-Schnürch,5 Ruth Prassl1,61Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria; 2Institute of Cell Biology, Histology, and Embryology, Medical University of Graz, Graz, Austria; 3Center for Medical Research, Medical University of Graz, Graz, Austria; 4Institute of Pharmaceutical Sciences/Pharmaceutical Technology, Karl-Franzens University, Graz, Austria; 5Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria; 6Ludwig Boltzmann Institute for Lung Vascular Research, Graz, AustriaAim: To develop mucoadhesive liposomes by anchoring the polymer chitosan-thioglycolic acid (chitosan-TGA to the liposomal surface to target intestinal mucosal membranes.Methods: Liposomes consisting of phosphatidylcholine (POPC and a maleimide-functionalized lipid were incubated with chitosan-TGA, leading to the formation of a thioether bond between free SH-groups of the polymer and maleimide groups of the liposome. Uncoated and newly generated thiomer-coated liposomes were characterized according to their size, zeta potential, and morphology using photon correlation spectroscopy and transmission electron microscopy. The release behavior of calcitonin and the fluorophore/quencher-couple ANTS/DPX (8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis- pyridinium bromide from coated and uncoated liposomes, was investigated over 24 hours in simulated gastric and intestinal fluids. To test the mucoadhesive properties of thiomer-coated and uncoated liposomes in-vitro, we used freshly excised porcine small intestine.Results: Liposomes showed a concentration-dependent increase in size – from approximately 167 nm for uncoated liposomes to 439 nm for the highest thiomer concentration used in this study. Likewise, their zeta potentials gradually increased from

pH-triggered echogenicity and contents release from liposomes.

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Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

2014-11-03

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

International Nuclear Information System (INIS)

Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

2016-01-01

Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

Energy Technology Data Exchange (ETDEWEB)

Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

2016-03-15

Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

Liposomal membrane disruption by means of miniaturized dielectric-barrier discharge in air: liposome characterization

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Svarnas, P.; Asimakoulas, L.; Katsafadou, M.; Pachis, K.; Kostazos, N.; Antimisiaris, S. G.

2017-08-01

The increasing interest of the plasma community in the application of atmospheric-pressure cold plasmas to bio-specimen treatment has led to the creation of the emerging field of plasma biomedicine. Accordingly, plasma setups based on dielectric-barrier discharges have already been widely tested for the inactivation of various cells. Most of these systems refer to the plasma jet concept where noble gases penetrate atmospheric air and are subjected to the influence of high electric fields, thus forming guided streamers. Following the original works of our group where liposomal membranes were proposed as models for studying the interaction between plasma jets and cells, we present herein a study on liposomal membrane disruption by means of miniaturized dielectric-barrier discharge running in atmospheric air. Liposomal membranes of various lipid compositions, lamellarities, and sizes are treated at different times. It is shown that the dielectric-barrier discharge of low mean power leads to efficient liposomal membrane disruption. The latter is achieved in a controllable manner and depends on liposome properties. Additionally, it is clearly demonstrated that liposomal membrane disruption takes place even after plasma extinction, i.e. during post-treatment, resembling thus an ‘apoptosis’ effect, which is well known today mainly for cell membranes. Thus, the adoption of the present concept would be beneficial for tailoring studies on plasma-treated cell-mimics. Finally, the liposome treatment is discussed with respect to possible physicochemical mechanisms and potential discharge modification due to the various compositions of the liquid electrode.

Solving Optimal Control Problem of Monodomain Model Using Hybrid Conjugate Gradient Methods

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Kin Wei Ng

2012-01-01

Full Text Available We present the numerical solutions for the PDE-constrained optimization problem arising in cardiac electrophysiology, that is, the optimal control problem of monodomain model. The optimal control problem of monodomain model is a nonlinear optimization problem that is constrained by the monodomain model. The monodomain model consists of a parabolic partial differential equation coupled to a system of nonlinear ordinary differential equations, which has been widely used for simulating cardiac electrical activity. Our control objective is to dampen the excitation wavefront using optimal applied extracellular current. Two hybrid conjugate gradient methods are employed for computing the optimal applied extracellular current, namely, the Hestenes-Stiefel-Dai-Yuan (HS-DY method and the Liu-Storey-Conjugate-Descent (LS-CD method. Our experiment results show that the excitation wavefronts are successfully dampened out when these methods are used. Our experiment results also show that the hybrid conjugate gradient methods are superior to the classical conjugate gradient methods when Armijo line search is used.

Chemical meningitis related to intra-CSF liposomal cytarabine.

Science.gov (United States)

Durand, Bénédicte; Zairi, Fahed; Boulanger, Thomas; Bonneterre, Jacques; Mortier, Laurent; Le Rhun, Emilie

2017-10-01

Therapeutic options of leptomeningeal metastases include intra-cerebrospinal fluid (CSF) chemotherapy. Among intra-CSF agents, liposomal cytarabine has advantages but can induce specific toxicities. A BRAF-V600E-mutated melanoma leptomeningeal metastases patient, treated by dabrafenib and liposomal cytarabine, presented after the first injection of liposomal cytarabine with hyperthermia and headaches. Despite sterile CSF/blood analyses, extended intravenous antibiotics were given and the second injection was delayed. The diagnosis of chemical meningitis was finally made. Dose reduction and appropriate symptomatic treatment permitted the administration of 15 injections of liposomal cytarabine combined with dabrafenib. A confirmation of the diagnosis of chemical meningitis is essential in order (1) not to delay intra-CSF or systemic chemotherapy or (2) to limit the administration of unnecessary but potentially toxic antibiotics.

A study on the modeling techniques using LS-INGRID

Energy Technology Data Exchange (ETDEWEB)

Ku, J. H.; Park, S. W

2001-03-01

For the development of radioactive material transport packages, the verification of structural safety of a package against the free drop impact accident should be carried out. The use of LS-DYNA, which is specially developed code for impact analysis, is essential for impact analysis of the package. LS-INGRID is a pre-processor for LS-DYNA with considerable capability to deal with complex geometries and allows for parametric modeling. LS-INGRID is most effective in combination with LS-DYNA code. Although the usage of LS-INGRID seems very difficult relative to many commercial mesh generators, the productivity of users performing parametric modeling tasks with LS-INGRID can be much higher in some cases. Therefore, LS-INGRID has to be used with LS-DYNA. This report presents basic explanations for the structure and commands, basic modelling examples and advanced modelling of LS-INGRID to use it for the impact analysis of various packages. The new users can build the complex model easily, through a study for the basic examples presented in this report from the modelling to the loading and constraint conditions.

Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients.

Science.gov (United States)

Lastrucci, Luciana; Bertocci, Silvia; Bini, Vittorio; Borghesi, Simona; De Majo, Roberta; Rampini, Andrea; Gennari, Pietro Giovanni; Pernici, Paola

2018-01-01

To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Physical and Oxidative Stability of Uncoated and Chitosan-Coated Liposomes Containing Grape Seed Extract

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Jochen Weiss

2013-08-01

Full Text Available Polyphenol-rich grape seed extract (0.1 w/w% was incorporated in liposomes (1 w/w% soy lecithin by high pressure homogenization (22,500 psi and coated with chitosan (0.1 w/w%. Primary liposomes and chitosan-coated secondary liposomes containing grape seed extract showed good physical stability during 98 days of storage. Most of the polyphenols were incorporated in the shell of the liposomes (85.4%, whereas only 7.6% of the polyphenols of grape seed extract were located in the interior of the liposomes. Coating with chitosan did not change the polyphenol content in the liposomes (86.6%. The uncoated liposomes without grape seed extract were highly prone to lipid oxidation. The cationic chitosan coating, however, improved the oxidative stability to some extent, due to its ability to repel pro-oxidant metals. Encapsulated grape seed extract showed high antioxidant activity in both primary and secondary liposomes, which may be attributed to its polyphenol content. In conclusion, the best chemical stability of liposomes can be achieved using a combination of grape seed extract and chitosan.

Fluorescence quenching of fluorescein by Merocyanine 540 in liposomes

International Nuclear Information System (INIS)

Toprak, Mahmut; Meryem Aydin, Burcu; Arik, Mustafa; Onganer, Yavuz

2011-01-01

The fluorescence quenching of fluorescein (FL) by merociyanine 540 (MC540) was examined in L-egg lecithin phosphatidycholine (PC) liposomes using spectroscopic methods. The type of quenching mechanism (dynamic or static) was evaluated using the Stern-Volmer plots. Findings were also supported by the temperature studies and florescence decay measurements. The Stern-Volmer equation was utilized to calculate bimolecular quenching constants (K q ). Furthermore, the bimolecular quenching constant of the quencher in the liposomes (K SV ), partition coefficient (K p ), binding constant (K), and corresponding thermodynamic parameters ΔH, ΔS, and ΔG were calculated. The quenching property was also used in determining quantitatively (K p ) the partition coefficient of Merociyanini 540 in PC liposome.The obtained data indicated that static quenching occurred in the system and the K SV values decreased with increasing lipid concentration. In addition, thermodynamic analysis suggested that van der Waals interactions and hydrogen bonding were the main acting forces between fluorescein and merociyanine 540 molecules in the medium. - Highlights: → Fluorescence quenching of FL by MC540 in liposome system was analyzed. → Fluorescence quenching mechanism of FL by MC540 was consistent with the static model. → Binding FL to MC540 was spontaneous and carried out by hydrogen bond and van der Waals forces.

Some aspects of geomagnetically conjugate phenomena

Energy Technology Data Exchange (ETDEWEB)

Rycroft, M.J.

1987-12-01

Both charged particles and waves convey information about the thermosphere, ionosphere and magnetosphere from the Northern to the Southern Hemisphere and vice versa, along geomagnetic flux tubes.The interhemispheric travel time of electrons or ions, being dependent upon L-value , pitch angle and energy (which may lie between less than or equal to 1 eV and greater than or equal to 1 MeV) may be many hours, ranging down to less than or equal to 1 s. However, the one-hop propagation time for magnetohydrodynamic or whistler mode waves generally lies between 10/sup 2/s and 1 s. Such times, therefore, give the time scales of transient phenomena that are geomagnetically conjugate and of changes in steady-state plasma processes occurring in geomagnetically conjugate regions. Contrasting examples are presented of conjugate physical phenomena, obtained using satellite, rocket, aircraft and ground-based observations; the latter capitalise upon the rather rare disposition of land - rather than ocean - at each end of a geophysically interesting flux tube. Particular attention is paid to the interactions between whistler mode waves and energetic electrons. Geomagnetic, radio, optical and plasma observations, taken together with model computations, provide a wealth of knowledge on conjugate phenomena and their dependence on conditions in the solar wind, substorms, L-value, etc... Finally, some suggestions are made for future lines of research.

Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

Science.gov (United States)

Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

2017-05-01

Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

Science.gov (United States)

Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

2005-01-01

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies

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Nivesh K. Mittal

2018-04-01

Full Text Available Doxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the malignant cells. The current research highlights the development and in vitro analysis of targeted liposomes containing AD 198. The best lipids were identified and optimized for physicochemical effects on the liposomal system. Physiochemical characteristics such as size, ζ-potential, and dissolution were also studied. Active targeting to CD22 positive cells was achieved by conjugating anti-CD22 Fab’ to the liposomal surface. Size and ζ-potential of the liposomes was between 115 and 145 nm, and −8 to−15 mV. 30% drug was released over 72 h. Higher cytotoxicity was observed in CD22+ve Daudi cells compared to CD22−ve Jurkat cells. The route of uptake was a clathrin- and caveolin-independent pathway. Intracellular localization of the liposomes was in the endolysosomes. Upon drug release, apoptotic pathways were activated partly by the regulation of apoptotic and oncoproteins such as caspase-3 and c-myc. It was observed that the CD22 targeted drug delivery system was more potent and specific compared to other untargeted formulations.

Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

Directory of Open Access Journals (Sweden)

Bhowmick Sudipta

2010-06-01

Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

Generation of fatty acids from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cardiolipin liposomes that stabilize recombinant human serum albumin.

Science.gov (United States)

Frahm, Grant E; Cameron, Brooke E; Smith, Jeffrey C; Johnston, Michael J W

2013-06-01

At elevated temperatures, studies have shown that serum albumin undergoes irreversible changes to its secondary structure. Anionic fatty acids and/or anionic surfactants have been shown to stabilize human serum albumin (HSA) against thermal denaturation through bridging hydrophobic domains and cationic amino acids residues of the protein. As albumin can readily interact with a variety of liposomes, this study proposes that cardiolipin delivered via 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes can improve the thermal stability of recombinant HSA produced in Saccharomyces cerevisiae (ScrHSA) in a similar manner to anionic fatty acids. Thermal stability and structure of ScrHSA in the absence and presence of DPPC/cardiolipin liposomes was assessed with U/V circular dichroism spectropolarimetry and protein thermal stability was confirmed with differential scanning calorimetry. Although freshly prepared DPPC/cardiolipin liposomes did not improve the stability of ScrHSA, DPPC/cardiolipin liposomes incubated at room temperature for 7 d (7dRT) dramatically improved the thermal stability of the protein. Mass spectrometry analysis identified the presence of fatty acids in the 7dRT liposomes, not identified in freshly prepared liposomes, to which the improved stability was attributed. The generation of fatty acids is attributed to either the chemical hydrolysis or oxidative cleavage of the unsaturated acyl chains of cardiolipin. By modulating the lipid composition through the introduction of lipids with higher acyl chain unsaturation, it may be possible to generate the stabilizing fatty acids in a more rapid manner.

Octanol-assisted liposome assembly on chip

NARCIS (Netherlands)

Deshpande, S.R.; Caspi, Y.; Meijering, A.E.C.; Dekker, C.

2016-01-01

Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5–20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin

ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

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Derkach SA

2015-04-01

Full Text Available Nowadays the vital problem of modern medicine is a tendency to emerging of both nosocomial and community-acquired strains before antibiotic resistance forming. The complexity of antibiotic therapy of diseases caused by methicillin resistant staphylococci having high poly resistance almost to every classes of antibacterial agents is of prime importance. One of the ways to improve antibacterial preparations still remains the development of their liposomal forms. This work studies antistaphylococcal activity (according to MIC of the liposomal form of lincomycin developed in the Institute of Dermatology and Venereology of Ukraine by Ivanova N. N., the Candidate of Сhemical Sciences.The purpose of this research work was to study liposomal inhibiting concentration of the liposomalny form of lincomycin and a commercial preparation lincomycin (produced by CJSC “Pharmaceutical firm "Darnitsa". Determination of the minimum inhibiting concentration was carried out by a tablet micromethod by consecutive cultivations of the samples under study.It is shown that MIC of liposomal lincomycin is eight times as low as usual lincomycin (0,23mkg/ml to 1,87 mkg/ml. Antibacterial activity of the liposomal form of lincomycin is studied concerning the patients selected from the different biotopes with pyo inflammatory diseases of staphylococcus strains (15 strains – methicillin sensitive, 12 strains - methicillin resistant.It is shown authentically the higher sensitivity of S. aureus strains to the liposomal form of lincomycin in comparison with usual lincomycin . Also 50.0% of MRSA strains were sensitive to the liposomalny form of lincomycin that shows the perspective for the development of the liposomal forms of antibiotics to cure staphylococcal infections.

Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells.

Science.gov (United States)

Nguyen, Minh-Hiep; Pham, Ngoc-Duy; Dong, Bingxue; Nguyen, Thi-Huynh-Nga; Bui, Chi-Bao; Hadinoto, Kunn

2017-11-01

While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation. The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon ® 90G). The blood cells were obtained from healthy male donors (n = 3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively. Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30 μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency). The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.

Boronated liposome development and evaluation

International Nuclear Information System (INIS)

Hawthorne, M.F.

1995-01-01

The boronated liposome development and evaluation effort consists of two separate tasks. The first is the development of new boron compounds and the synthesis of known boron species with BNCT potential. These compounds are then encapsulated within liposomes for the second task, biodistribution testing in tumor-bearing mice, which examines the potential for the liposomes and their contents to concentrate boron in cancerous tissues

Radiolabeling of liposomes and polymeric micelles with PET-isotopes

Energy Technology Data Exchange (ETDEWEB)

Ingemann Jensen, A.T.

2013-06-01

This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

Radiolabeling of liposomes and polymeric micelles with PET-isotopes

International Nuclear Information System (INIS)

Ingemann Jensen, A.T.

2013-01-01

This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

Significance of Cultural-Historical Theory of Psychological Development of L.S. Vygotsky for the Development of Modern Models of Social Cognition and Psychotherapy

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Kholmogorova A.B.,

2016-12-01

Full Text Available The article acknowledges the situation of methodical crisis in modern research of social cognition related to the domination of reductive approaches that ignore the uniqueness of human psyche. Heuristicity of concepts of cultural-historical theory of psychological development of L.S. Vygotsky, which serves to overcome the apparent inconsistencies is substantiated. Models of social cognition based on the principles of cultural-historical psychology are described, those being the model of social cognition within phylogenesis of M. Tomasello, and the model of social cognition within ontogenesis of C. Fernyhough. Current situation in the area of mental health is reviewed from the standpoint of cultural-historical psychology, its specifics reflected in the increased burden on reflexive functions, that is, skills lying within the sphere of social cognition is substantiated. Modern psychotherapeutic apparatus directed to compensate social cognition deficits due to various psychiatric disorders is reviewed. The assumption that adolescense is sensitive period for the development of higher forms of social cognition is made, and a summary of researches supporting this assertion is presented. Main contradictions of modern-day maturing are enunciated. To conclude the presented theoretical analysis, a comprehensive multiple-factor model of social cognition is presented based on concepts of cultural-historical theory of L.S. Vygotsky.

Effect of Co-overexpression of Nisin Key Genes on Nisin Production Improvement in Lactococcus lactis LS01.

Science.gov (United States)

Ni, Zhi-Jian; Zhang, Xiao-Yuan; Liu, Fei; Wang, Miao; Hao, Rong-Hua; Ling, Pei-Xue; Zhu, Xi-Qiang

2017-06-01

Nisin is a small antimicrobial peptide produced by several subset strains of Lactococcus lactis. To improve nisin yield in the producer L. lactis LS01, we proposed a successive fusion of nisA with nisRK and nisFEG into a single shuttle expression vector pMG36e under the control of the native strong constitutive promoter p32. Subsequently, the recombinant vectors were transplanted into the producer cell through electroporation. Nisin productivity was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis and bioactivity assays. Expression of nisin peptide was detected by agar diffusion bioassay, and the transcriptional levels of the target genes involved in nisin biosynthesis were investigated via semi-quantitative reverse transcription PCR expression analysis using 16S ribosomal RNA (rRNA) as an internal control. Results suggested that the introduction of empty plasmid did not affect nisin production of L. lactis LS01, whereas by our rational construction and screening, the engineered strain co-overexpressing nisA, nisRK, and nisFEG achieved a maximum increment in bioactive nisin production with a yield of 2470 IU/ml in shake flasks and 4857 IU/ml in 1.0-l fermenters, which increased by approximately 66.3 and 52.6% (P < 0.05), respectively, compared with that of the original strain under the given fermentation conditions. Meanwhile, the transcriptional analysis revealed that the expression of most of these multicopy genes except nisE at transcriptional level were upregulated in the two recombinant strains (LS01/pAR and LS01/pARF), possibly contributing to the improved nisin production. Therefore, this study would provide a potential strategy to improve the economic benefits of nisin manufacture for large-scale industrial production.

pH dependent antioxidant activity of lettuce (L. sativa) and synergism with added phenolic antioxidants.

Science.gov (United States)

Altunkaya, Arzu; Gökmen, Vural; Skibsted, Leif H

2016-01-01

Influence of pH on the antioxidant activities of combinations of lettuce extract (LE) with quercetin (QC), green tea extract (GTE) or grape seed extract (GSE) was investigated for both reduction of Fremy's salt in aqueous solution using direct electron spin resonance (ESR) spectroscopy and in L-α-phosphatidylcholine liposome peroxidation assay measured following formation of conjugated dienes. All examined phenolic antioxidants showed increasing radical scavenging effect with increasing pH values by using both methods. QC, GTE and GSE acted synergistically in combination with LE against oxidation of peroxidating liposomes and with QC showing the largest effect. The pH dependent increase of the antioxidant activity of the phenols is due to an increase of their electron-donating ability upon deprotonation and to their stabilization in alkaline solutions leading to polymerization reaction. Such polymerization reactions of polyphenolic antioxidants can form new oxidizable -OH moieties in their polymeric products resulting in a higher radical scavenging activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Microbial Carbonate Precipitation by Synechococcus PCC8806, LS0519 and Synechocystis PCC6803 on Concrete Surfaces and in Low Saturation Solution

Science.gov (United States)

Zhu, T.; Lin, Y.; Dittrich, M.

2015-12-01

Microbial carbonate precipitation (MCP) by cyanobacteria has been recognized in a variety of environment such as freshwater, marine, cave, and even desert. Recently, their calcification potential has been tested in an emerging technology-- bioconcrete. This study is to explore the calcification by three cyanobacteria strains under different environmental conditions. Experiment A was carried out in 2mM NaHCO3 and 5mM CaCl2, with a cell concentration of 107 cells L-1. In experiment B, one side of the concrete surface was treated with bacteria and then immersed in the solution containing 0.4 mM NaHCO3 and 300 mM CaCl2. In experiment A, the pH of the abiotic condition remained constant around 8.55, while that of biotic conditions increased by 0.15 units in the presence of LS0519, and by 0.3 units in the presence of PCC8806 or PCC6803 within 8 hours. Over a period of 30 hours, PCC8806, LS0519 and PCC6803 removed 0.1, 0.12 and 0.2 mM calcium from the solution respectively. After 30 hours, the alkalinity of the solution decreased by 30 mg/L, 10 mg/L and 5 mg/L respectively in the presence of PCC6803, LS0519 and PCC8806. Under scanning electron microscopy (SEM), no precipitate was found in the abiotic condition, while calcium carbonate was associated by all the three strains. Among them, PCC6803 precipitated more carbonates. In experiment B, LS0519 and PCC8806 increased the pH with a value of 0.25, while PCC6803 increased the pH by 0.33 units. SEM shows LS0519 was less likely attached to the concrete surface. Neither did the precipitates on concrete surface differ from that in the abiotic condition. In comparison, PCC8806 and PCC6803 were closely associated with 8-μm porous precipitates. Cells were either found enclosed in precipitates or connecting two precipitates. In conclusion, all the three strains triggered the calcium carbonate precipitation. LS0519 has a little impact on the carbonate precipitation in the solution, but negligent influence on the concrete surface

Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.

NARCIS (Netherlands)

Commandeur, J.N.M.; Boogaard, P.J.; Mulder, G.J.; Vermeulen, N.P.E.

1991-01-01

The mutagenicity, cytotoxicity and metabolism of two regioisomic l-cysteine- and N-acetyl-l-cysteine-S-conjugates of trichloroethylene were studied. The 1,2-dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella

ICEApl1, an integrative conjugative element related to ICEHin1056, identified in the pig pathogen Actinobacillus pleuropneumoniae

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Janine T Bosse

2016-06-01

Full Text Available ICEApl1 was identified in the whole genome sequence of MIDG2331, a tetracycline-resistant (MIC = 8 mg/L serovar 8 clinical isolate of Actinobacillus pleuropneumoniae, the causative agent of porcine pleuropneumonia. PCR amplification of virB4, one of the core genes involved in conjugation, was used to identify other A. pleuropneumoniae isolates potentially carrying ICEApl1. MICs for tetracycline were determined for virB4 positive isolates, and shotgun whole genome sequence analysis was used to confirm presence of the complete ICEApl1. The sequence of ICEApl1 is 56083 bp long and contains 67 genes including a Tn10 element encoding tetracycline resistance. Comparative sequence analysis was performed with similar integrative conjugative elements (ICEs found in other members of the Pasteurellaceae. ICEApl1 is most similar to the 59393 bp ICEHin1056, from Haemophilus influenzae strain 1056. Although initially identified only in serovar 8 isolates of A. pleuropneumoniae (31 from the UK and 1 from Cyprus, conjugal transfer of ICEApl1 to representative isolates of other serovars was confirmed. All isolates carrying ICEApl1 had a MIC for tetracycline of 8 mg/L. This is, to our knowledge, the first description of an ICE in A. pleuropneumoniae, and the first report of a member of the ICEHin1056 subfamily in a non-human pathogen. ICEApl1 confers resistance to tetracycline, currently one of the more commonly used antibiotics for treatment and control of porcine pleuropneumonia.

Evaluation of Extrusion Technique for Nanosizing Liposomes

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Sandy Gim Ming Ong

2016-12-01

Full Text Available The aim of the present study was to study the efficiency of different techniques used for nanosizing liposomes. Further, the aim was also to evaluate the effect of process parameters of extrusion techniques used for nanosizing liposomes on the size and size distribution of the resultant liposomes. To compare the efficiency of different nanosizing techniques, the following techniques were used to nanosize the liposomes: extrusion, ultrasonication, freeze-thaw sonication (FTS, sonication and homogenization. The extrusion technique was found to be the most efficient, followed by FTS, ultrasonication, sonication and homogenization. The extruder used in the present study was fabricated using readily available and relatively inexpensive apparatus. Process parameters were varied in extrusion technique to study their effect on the size and size distribution of extruded liposomes. The results obtained indicated that increase in the flow rate of the extrusion process decreased the size of extruded liposomes however the size homogeneity was negatively impacted. Furthermore, the liposome size and distribution was found to decline with decreasing membrane pore size. It was found that by extruding through a filter with a pore size of 0.2 µm and above, the liposomes produced were smaller than the pore size, whereas, when they were extruded through a filter with a pore size of less than 0.2 µm the resultant liposomes were slightly bigger than the nominal pore size. Besides that, increment of extrusion temperature above transition temperature of the pro-liposome had no effect on the size and size distribution of the extruded liposomes. In conclusion, the extrusion technique was reproducible and effective among all the methods evaluated. Furthermore, processing parameters used in extrusion technique would affect the size and size distribution of liposomes. Therefore, the process parameters need to be optimized to obtain a desirable size range and homogeneity

Near infrared photoimmunotherapy with avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody.

Science.gov (United States)

Nagaya, Tadanobu; Nakamura, Yuko; Sato, Kazuhide; Harada, Toshiko; Choyke, Peter L; Hodge, James W; Schlom, Jeffrey; Kobayashi, Hisataka

2017-01-31

Near Infrared-Photoimmunotherapy (NIR-PIT) is a highly selective tumor treatment that employs an antibody-photo-absorber conjugate (APC). Programmed cell death protein-1 ligand (PD-L1) is emerging as a molecular target. Here, we describe the efficacy of NIR-PIT, using fully human IgG1 anti-PD-L1 monoclonal antibody (mAb), avelumab, conjugated to the photo-absorber, IR700DX, in a PD-L1 expressing H441 cell line, papillary adenocarcinoma of lung. Avelumab-IR700 showed specific binding and cell-specific killing was observed after exposure of the cells to NIR in vitro. In the in vivo study, avelumab-IR700 showed high tumor accumulation and high tumor-background ratio. Tumor-bearing mice were separated into 4 groups: (1) no treatment; (2) 100 μg of avelumab-IR700 i.v.; (3) NIR light exposure only, NIR light was administered; (4) 100 μg of avelumab-IR700 i.v., NIR light was administered. Tumor growth was significantly inhibited by NIR-PIT treatment compared with the other groups (p avelumab, is suitable as an APC for NIR-PIT. Furthermore, NIR-PIT with avelumab-IR700 is a promising candidate of the treatment of PD-L1-expressing tumors that could be readily translated to humans.

Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

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Xiao-juan LIU

2013-07-01

Full Text Available Objective　To prepare luteinizing hormone-releasing hormone a (LHRHa targeted Bruceajavanicaliposomes and evaluate its quality. Methods　The LHRHa-targeted Bruceajavanicaliposome was prepared by thin layer dispersion together with biotin¬streptavidin bridge method. The optimum formation was selected by means of orthogonal design of experiment. The morphology of liposome was observed with transmission electron microscope. Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential. The entrapment efficiency was determined by ultra-violet spectroscopy and column chromatography. Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability. The targeting ability of liposome was appraised by cell experiment in vitro. Results　The formed optimum formula was as follows: the ratio of lecithin to cholesterol was 4:1, Brucea javanicaoil:lipid was 3:10, DSPE-PEG (2000-Biotin:lecithin content was 3%, ultrasonic-homogenized for 8 minutes. Liposomes were round in shape, the average diameter and zeta potential of liposome were 155.1±14.5mm and –(24.1±0.54 mV, respectively. The average entrapment efficiency was 92.2%. Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes. Conclusion　The technique of preparing LHRHa-targeted Bruceajavanicaliposome is suitable, and high in entrapment efficiency, with good stability and targeting ability.

Preparation and properties of functional mixed-lipid liposomes by γ-ray irradiation

International Nuclear Information System (INIS)

Hosoi, Fumio; Omichi, Hideki; Akama, Kazuhiro; Awai, Kouji; Yano, Yoshihiro; Nakano, Yoshio

1998-01-01

The feature of mixed-lipid liposomes such as polymerization and polymerized liposomes stability were investigated to find means for producing red cells containing hemoglobin inside the liposomes. The surface pressure-area isotherm values of the mixed-lipid monolayer indicated 1-stearoyl-2-(2,4-octadecadienoyl)-glycero-3-phosphocholine (SOPC) to be immiscible in cholesterol (Chol) and stearic acid (SA), and each component to contain separate domains in the bilayer membrane of liposomes. Radiation induced polymerization of mixed-SOPC liposomes was carried out using γ-rays from 60 Co at 4degC to stabilize lipid bilayers. The polymer yield increased significantly by adding Chol and SA to SOPC. The rate of polymerization of SOPC liposomes increased linearly with increasing of dose rate. The molecular weight of the polymer decreased with an increase in irradiation time. Irradiated SOPC/Chol/SA liposome vesicle size was affected by freeze-thawing. The vesicle size did not change when SOPC/Chol/SA was present in the system due to the addition of immiscible saturated 1,2-dipalmitoyl-glycero-3-phosphocholine (DPPC). (author)

Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy

Energy Technology Data Exchange (ETDEWEB)

Wang, Meili; Zhao, Tingting; Liu, Yanping; Wang, Qianqian; Xing, Shanshan; Li, Lei; Wang, Longgang [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China); Liu, Lanxiang [The First Hospital of Qinhuangdao, No. 258 Cultural Road, Qinhuangdao 066000 (China); Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China)

2017-02-01

There are tremendous challenges on antitumor and its therapeutic drugs, and preparation of highly efficient nano-vehicles represents one of the novel topics in antitumor pharmaceutical field. Herein, the novel chitosan-coated ursolic acid (UA) liposome (CS-UA-L) was efficiently prepared with highly tumor targeting, drug controlled release and low side-effect. The CS-UA-L was uniformly spherical particles with diameter of ~ 130 nm, and the size was more easily trapped into the tumor tissues. Chitosan modification can make liposomes carrying positive charges, which were inclined to combine with the negative charges on the surface of tumor cells, and then the CS-UA-L could release UA rapidly at pH 5.0 comparing with pH 7.4. Meanwhile, the CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells and significantly antitumor activity (61.26%) in mice bearing U14 cervical cancer. The tumor tissues of CS-UA-L treated mice had enhanced cell apoptosis, extensive necrosis and low cell proliferation activity. These results demonstrated that the multifunctional CS-UA-L allowed a precision treatment for localized tumor, and reducing the total drug dose and side-effect, which hold a great promise in new safe and effective tumor therapy. - Graphical abstract: Schematic diagram representing the principle of synthesis of CS-UA-L and pH-triggered sequential UA release after treatment on tumor bearing mouse. - Highlights: • The novel chitosan-coated ursolic acid liposomes (CS-UA-L) were successfully prepared. • CS-UA-L possessed sensitive pH-response, which could release UA rapidly at pH 5.0 comparing with pH 7.4. • CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells than UA and UA-L. • CS-UA-L suppressed tumor growth more efficiently than those with UA and UA-L in mice bearing U14 cervical cancer. • The CS-UA-L allow for precision treatment of the tumor and potential to reduce the total drug dose and side-effect.

Lymphatic uptake and biodistribution of liposomes after subcutaneous injection - IV. Fate of liposomes in regional lymph nodes

NARCIS (Netherlands)

Oussoren, C; Scherphof, G; van der Want, JJ; van Rooijen, N; Storm, G

1998-01-01

The ability of clodronate-containing liposomes to deplete lymph nodes of macrophages was used as a tool to investigate the fate of liposomes in regional lymph nodes after subcutaneous (s.c.) administration. Reduced lymph node localization of liposomes in macrophage-depleted lymph nodes confirmed

Comments on the note by L.S. Nelson: ''unusually high (oxidizer/Pu) ratios in the macro-residues from plutonium droplet combustion''

International Nuclear Information System (INIS)

Allen, M.D.; Morgan, L.G.

1982-01-01

An alternative explanation for unusually high ratios of oxidizers/plutonium in the residues from plutonium droplet combustion is offered in response to a note by L.S. Nelson. Two additional experiments are suggested that would be helpful in clarifying the high oxidizer/Pu ratios. The first would be to measure the true surface area for a spherule after its explosion. The second is an experiment analogous to a gas analysis experiment. The conclusion is put forth that adsorbed gases are the most likely cause of the high O/M ratios described by Nelson

Stimuli-Responsive Liposomes for Controlled Drug Delivery

KAUST Repository

Li, Wengang

2014-09-01

Liposomes are promising drug delivery vesicles due to their biodegradibility, large volume and biocompatibility towards both hydrophilic and hydrophobic drugs. They suffer, however, from poor stability which limits their use in controlled delivery applications. Herein, a novel method was devised for modification of liposomes with small molecules, polymers or nanoparticles to afford stimuli responsive systems that release on demand and stay relatively stable in the absence of the trigger.. This dissertation discusses thermosensitive, pH sensitive, light sensitive and magnetically triggered liposomes that have been prepared for controlled drug delivery application. RAFT polymerization was utilized for the preparation of thermosensitive liposomes (Cholesterol-PNIPAm) and acid-labile liposomes (DOPE-PAA). With low Mw Cholesterol-PNIPAm, the thermosensitive liposomes proved to be effective for controlled release and decreased the cytotoxicity of PNIPAm by eliciting the polymer doses. By crosslinking the DOPE-PAA on liposome surface with acid-labile diamine linkers, DOPE-PAA liposomes were verified to be sensitive at low pH. The effects of polymer structures (linear or hyperbranched) have also been studied for the stability and release properties of liposomes. Finally, a dual-responsive Au@SPIO embedded liposome hybrid (ALHs) was prepared with light-induced “on-and-off” function by photo-thermal process (visible light) and instant release properties triggered by alternating magnetic field, respectively. The ALH system would be further applied into the cellular imaging field as MRI contrast agent.

Influence of polymer size, liposomal composition, surface charge, and temperature on the permeability of pH-sensitive liposomes containing lipid-anchored poly(2-ethylacrylic acid

Directory of Open Access Journals (Sweden)

Lu T

2012-09-01

Full Text Available Tingli Lu,1 Zhao Wang,2 Yufan Ma,1 Yang Zhang,2 Tao Chen1,21Key Laboratory for Space Bioscience and Biotechnology, School of Life Science, Northwestern Polytechnical University, 2Liposome Research Centre, Xi'an, ChinaBackground: Liposomes containing pH-sensitive polymers are promising candidates for the treatment of tumors and localized infection. This study aimed to identify parameters influencing the extent of contents release from poly(ethylacrylic acid (PEAA vesicles, focusing on the effects of polymer size, lipid composition, vesicle surface charge, and temperature.Methods: Anchored lipid pH-sensitive PEAA was synthesized using PEAA with a molecular weight of 8.4 kDa. PEAA vesicles were prepared by insertion of the lipid-anchored PEAA into preformed large unilamellar vesicles. The preformed liposomes were manipulated by varying the phosphocholine and cholesterol content, and by adding negative or positive charges to the liposomes. A calcein release assay was used to evaluate the effects of polymer size, liposome composition, surface charge, and temperature on liposomal permeability.Results: The release efficiency of the calcein-entrapped vesicles was found to be dependent on the PEAA polymer size. PEAA vesicles containing a phosphatidylcholine to cholesterol ratio of 60:40 (mol/mol released more than 80% of their calcein content when the molecular weight of PEAA was larger than 8.4 kDa. Therefore, the same-sized polymer of 8.4 kDa was used for the rest of study. The calcein release potential was found to decrease as the percentage of cholesterol increased and with an increase in the phosphocholine acyl chain length (DMPC . DPPC . DSPC. Negatively charged and neutral vesicles released similar amounts of calcein, whereas positively charged liposomes released a significant amount of their contents. pH-sensitive release was dependent on temperature. Dramatic content release was observed at higher temperatures.Conclusion: The observed

Preliminary study of corneal penetration of /sup 125/I-labelled idoxuridine liposome

Energy Technology Data Exchange (ETDEWEB)

Dharma, S.K.; Fishman, P.H.; Peyman, G.A.

1986-01-01

We compared corneal penetration of idoxuridine (IDU) to liposome-encapsulated IDU. Liposomes of phosphatidic acid, phosphatidyl choline and alphatocopherol in a molar ratio 1:8:1 were prepared using the reverse phase evaporation method. New Zealand albino rabbits received either 0.1% solution of I/sup 125/-labelled aqueous IDU or liposome-encapsulated IDU topically every 2 min for 6 min. Corneal, aqueous, and vitreous samples were assayed for I/sup 125/ radioactivity at 15 min and at 1, 2, 3, and 6 h following drug application. Our results indicated that corneal penetration of liposomal IDU was significantly increased over the regular form of the drug for a time interval of 6 h.

A preliminary study of corneal penetration of 125I-labelled idoxuridine liposome

International Nuclear Information System (INIS)

Dharma, S.K.; Fishman, P.H.; Peyman, G.A.

1986-01-01

We compared corneal penetration of idoxuridine (IDU) to liposome-encapsulated IDU. Liposomes of phosphatidic acid, phosphatidyl choline and alphatocopherol in a molar ratio 1:8:1 were prepared using the reverse phase evaporation method. New Zealand albino rabbits received either 0.1% solution of I 125 -labelled aqueous IDU or liposome-encapsulated IDU topically every 2 min for 6 min. Corneal, aqueous, and vitreous samples were assayed for I 125 radioactivity at 15 min and at 1, 2, 3, and 6 h following drug application. Our results indicated that corneal penetration of liposomal IDU was significantly increased over the regular form of the drug for a time interval of 6 h. (author)

Interplays between Sumoylation, SUMO-Targeted Ubiquitin Ligases, and the Ubiquitin-Adaptor Protein Ufd1 in Fission Yeast

DEFF Research Database (Denmark)

Køhler, Julie Bonne

and the specific molecular interactions and sequence of events linking sumoylation, ubiquitylation and substrate degradation, has been largely uncovered. Using the fission yeast model organism I here present evidence for a role of the Ufd1 (ubiquitinfusion degradation 1) protein, and by extension of the Cdc48-Ufd1...... proteasome mediates direct cross-talk between the two modification systems. By contributing to the dynamic turnover of SUMO conjugated species these SUMO-targeted ubiquitin ligases (STUbLs) fulfills essential roles in both yeast and man. However, the specific sumoylated proteins affected by STUbL activity...... either in STUbL or Ufd1 function. In addition to identifying more than 900 unique sumoylated sites, these efforts revealed a number of proteins with upregulated sumoylation either in STUbL and/or Ufd1 mutant cells. These findings propose specific candidate substrates through which STUbL and Cdc48-Ufd1...

Treatment of deep mycoses with liposomal amphotericin B.

Science.gov (United States)

Berenguer, J; Muñoz, P; Parras, F; Fernández-Baca, V; Hernández-Sampelayo, T; Bouza, E

1994-06-01

Amphotericin B is the mainstay of therapy of many deep mycoses, but its use is seriously hampered by dose-limiting nephrotoxicity. In this study a liposomal formulation of amphotericin B was administered to ten patients with proven deep mycoses: invasive aspergillosis (n = 4), deep candidiasis (n = 4) and zygomycosis (n = 2). The mean daily dosage of liposomal amphotericin B was 3.0 mg/kg (range 2.5 to 4 mg/kg), the mean total dosage of liposomal amphotericin B 2,781 mg (range 87 to 5,220 mg) and the mean duration of treatment 17 days (range 3 to 33 days). Treatment with liposomal amphotericin B was associated with little nephrotoxicity and an overall survival rate of 50%. The median increase of serum creatinine from baseline levels was 0.38 mg/dl (-1.2 to 2.6 mg/dl).

Lipid raft-like liposomes used for targeted delivery of a chimeric entry-inhibitor peptide with anti-HIV-1 activity.

Science.gov (United States)

Gómara, María José; Pérez-Pomeda, Ignacio; Gatell, José María; Sánchez-Merino, Victor; Yuste, Eloisa; Haro, Isabel

2017-02-01

The work reports the design and synthesis of a chimeric peptide that is composed of the peptide sequences of two entry inhibitors which target different sites of HIV-1 gp41. The chimeric peptide offers the advantage of targeting two gp41 regions simultaneously: the fusion peptide and the loop both of which are membrane active and participate in the membrane fusion process. We therefore use lipid raft-like liposomes as a tool to specifically direct the chimeric inhibitor peptide to the membrane domains where the HIV-1 envelope protein is located. Moreover, the liposomes that mimic the viral membrane composition protect the chimeric peptide against proteolytic digestion thereby increasing the stability of the peptide. The described liposome preparations are suitable nanosystems for managing hydrophobic entry-inhibitor peptides as putative therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

Presence of electrostatically adsorbed polysaccharides improves spray drying of liposomes.

Science.gov (United States)

Karadag, Ayse; Özçelik, Beraat; Sramek, Martin; Gibis, Monika; Kohlus, Reinhard; Weiss, Jochen

2013-02-01

Spray drying of liposomes with conventional wall materials such as maltodextrins often yields nonfunctional powders, that is, liposomes break down during drying and rehydration. Electrostatically coating the surface of liposomes with a charged polymer prior to spray drying may help solve this problem. Anionic lecithin liposomes (approximately 400 nm) were coated with lower (approximately 500 kDa, LMW-C) or higher (approximately 900 kDa, HMW-C) molecular weight cationic chitosan using the layer-by-layer depositing method. Low (DE20, LMW-MD) or high molecular weight (DE2, HMW-MD) maltodextrin was added as wall material to facilitate spray drying. If surfaces of liposomes (1%) were completely covered with chitosan (0.4%), no bridging or depletion flocculation would occur, and mean particle diameters would be approximately 500 nm. If maltodextrins (20%) were added to uncoated liposomes, extensive liposomal breakdown would occur making the system unsuitable for spray drying. No such aggregation or breakdown was observed when maltodextrin was added to chitosan-coated liposomes. Size changed little or even decreased slightly depending on the molecular weight of maltodextrin added. Scanning electron microscopy images of powders containing chitosan-coated liposomes revealed that their morphologies depended on the type of maltodextrin added. Powders prepared with LMW-MD contained mostly spherical particles while HMW-MD powders contained particles with concavities and dents. Upon redispersion, coated liposomes yielded back dispersions with particle size distributions similar to the original ones, except for LMW-C coated samples that had been spray dried with HMW-MD which yielded aggregates (approximately 30 μm). Results show that coating of liposomes with an absorbing polymer allows them to be spray dried with conventional maltodextrin wall materials. Liposomes have attracted considerable attention in the food and agricultural, biomedical industries for the delivery of

Liposomes containing cationic dimethyl dioctadecyl ammonium bromide: formulation, quality control, and lipofection efficiency.

Science.gov (United States)

Dass, Crispin R; Walker, Todd L; Burton, Mark A

2002-01-01

This article describes a novel, simple, and relatively inexpensive method to prepare cationic liposomes using an ethanol injection/pressure extrusion method. The study also demonstrated that binding erythrosine dye to cationic liposomes results in a shift of the absorption maximum of the dye from 528 nm to 549 nm at pH 4.25, allowing quantification and visualization of these vesicles. In addition, a relatively simple Ficoll-based gradient centrifugation method for separation of lipoplexes from unbound molecules is presented. Laboratory-formulated dimethyl dioctadecyl ammonium bromide (DDAB) containing liposomes were just as efficient in complexing nucleic acids as commercially available types, and binding increased as the positive to neutral lipid ratio was increased. Transfection efficiency of the DDAB-containing liposomes increased as the ratio of cationic to neutral lipid was increased from 1:1 to 4:1 with either PtdChol or DOPE as the neutral lipid. A concomitant increase in cytotoxicity of CSU-SA1 cancer cells was noted as the ratio of positive to neutral lipid of the liposomes was increased. Nevertheless, our present study showed that the 2:1 liposome is a good choice since it delivers functional plasmids at a comparable rate to commercial liposome formulations, has similar toxicities to the less harmful commercial liposomes, and is at least 1000-fold more economical to prepare inhouse, a major factor to be considered in preclinical and clinical studies with these carriers.

An extended hybrid density functional (X3LYP) with improved descriptions of nonbond interactions and thermodynamic properties of molecular systems

Science.gov (United States)

Xu, Xin; Zhang, Qingsong; Muller, Richard P.; Goddard, William A.

2005-01-01

We derive here the form for the exact exchange energy density for a density that decays with Gaussian-type behavior at long range. This functional is intermediate between the B88 and the PW91 exchange functionals. Using this modified functional to match the form expected for Gaussian densities, we propose the X3LYP extended functional. We find that X3LYP significantly outperforms Becke three parameter Lee-Yang-Parr (B3LYP) for describing van der Waals and hydrogen bond interactions, while performing slightly better than B3LYP for predicting heats of formation, ionization potentials, electron affinities, proton affinities, and total atomic energies as validated with the extended G2 set of atoms and molecules. Thus X3LYP greatly enlarges the field of applications for density functional theory. In particular the success of X3LYP in describing the water dimer (with Re and De within the error bars of the most accurate determinations) makes it an excellent candidate for predicting accurate ligand-protein and ligand-DNA interactions.

CÁLCULO AUTOMÁTICO DO FATOR TOPOGRÁFICO (LS DA EUPS, NA BACIA DO RIO PARACATU AUTOMATIC CALCULATION OF THE TOPOGRAPHIC FACTOR (LS OF THE USLE, IN THE PARACATU RIVER BASIN

Directory of Open Access Journals (Sweden)

Valtercides Cavalcante da Silva

2007-09-01

Full Text Available

Embora a equação universal de perda de solo (EUPS seja amplamente utilizada na predição de perda de solo, é difícil obter certos fatores dessa equação em bacias hidrográficas, como é o caso do fator de comprimento de vertente (fator L. Diante disso, este trabalho objetivou determinar de maneira informatizada (automática, o fator topográfico (LS da EUPS, utilizando para o cálculo do fator L o algoritmo de Desmet & Govers (1996, com o suporte de um Sistema de Informações Geográficas (SIG. Verificou-se a viabilidade do cálculo do fator de comprimento de vertente, na escala de 1:100.000, por meio da metodologia desses autores, que considera o fluxo acumulado.

Although the Universal Soil Loss Equation (USLE is widely used all over the world in the prediction of soil loss, a few factors of the equation are difficult to obtain, such as the slope length factor (L factor, particularly in watersheds. For this reason, the purpose of the present research was to apply the methodology for automatic calculation of the topographic factor (LS factor using the algorithm developed by Desmet and Govers (1996 which defines the slope length factor (L factor through the Geographic Information System (GIS. It was verified that the slope length factor (L, as developed by Desmet and Govers (1996, which accounts for accumulated flow, showed feasible results.

KEY-WORDS: USLE; L factor; topographic factor; GIS.

Preparation of 99mTc-HYNIC-PEG-liposomes for imaging of the focal sites infection

International Nuclear Information System (INIS)

Hong, Jun Pyo; Awh, Ok Doo; Kim, Hyun Suk; Lee, Eun Sook; Lee, Tae Sup; Choi, Tae Hyun; Choi, Chang Woon; Lim, Sang Moo

2002-01-01

A new linker, hydrazino nicotinamide (HYNIC), was recently introduced for labelling of liposome with 99m Tc. In this study we synthesized HYNIC derivatized PEG (polyethylene glycol)-liposomes radiolabeled with 99m Tc. In order to synthesize HYNIC-DSPE (distearoyl phosphatidyl ethanolamine) which is a crucial component for 99m Tc chelation, first of all succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized from 6-chloronicotinic acid by three sequential reactions. A DSPE derivative of succinimidyl 6-BOC-hydrazinopyridine-3-carboxylic acid was transformed into HYNIC-DSPE by HCI/dioxane. HYNIC-PEG-liposomes were prepared by hydration of the dried lipid mixture of EPC (egg phosphatidyl choline): PEG-DSPE : HYNIC-DSPE: cholesterol (1.85:0.15:0.07:1, molar ratio). The HYNIC-PEG-liposomes were labeled with 99m Tc in the presence of SnCl 2 ·2H 2 O (a reducing agent) and tricine (a colignad). To investigate the level of in vivo transchelation of 99m Tc in the liposomes, the 99m Tc-HYNIC-PEG-liposomes were incubated with a molar excess of DTPA, cysteine or glutathione solutions at 37 .deg. C for 24 hours. 6-BOC-hydrazinopyridine-3-carboxylic acid was synthesized with 77.3% overall yield. The HYNIC concentration in the PEG-coated liposome dispersion was 1.08 mM. In condition of considering the measured liposome size of 106 nm, the phospholipid concentration of 77.5 μmol/ ml and the liposomal particle number of 5.2x10 14 liposomes/ml, it is corresponded to approximate 1,250 nicotinyl hydrazine group per liposome in HYNIC-PEG-liposome. The removal of free 99m Tc was not necessary because the labeling efficiency were above 99%. The radiolabeled liposomes maintained 98%, 96% and 99%, respectively, of radioactivity after incubation with transchelators. The radiolabeled liposomes possessed above 90% of the radioactivity in serum. These results suggest that the HYNIC can be synthesized easily and applied in labelling of PEG-liposomes with 99m Tc

Ultrasound, liposomes, and drug delivery: principles for using ultrasound to control the release of drugs from liposomes.

Science.gov (United States)

Schroeder, Avi; Kost, Joseph; Barenholz, Yechezkel

2009-11-01

Ultrasound is used in many medical applications, such as imaging, blood flow analysis, dentistry, liposuction, tumor and fibroid ablation, and kidney stone disruption. In the past, low frequency ultrasound (LFUS) was the main method to downsize multilamellar (micron range) vesicles into small (nano scale) unilamellar vesicles. Recently, the ability of ultrasound to induce localized and controlled drug release from liposomes, utilizing thermal and/or mechanical effects, has been shown. This review, deals with the interaction of ultrasound with liposomes, focusing mainly on the mechanical mechanism of drug release from liposomes using LFUS. The effects of liposome lipid composition and physicochemical properties, on one hand, and of LFUS parameters, on the other, on liposomal drug release, are addressed. Acoustic cavitation, in which gas bubbles oscillate and collapse in the medium, thereby introducing intense mechanical strains, increases release substantially. We suggest that the mechanism of release may involve formation and collapse of small gas nuclei in the hydrophobic region of the lipid bilayer during exposure to LFUS, thereby inducing the formation of transient pores through which drugs are released. Introducing PEG-lipopolymers to the liposome bilayer enhances responsivity to LFUS, most likely due to absorption of ultrasonic energy by the highly hydrated PEG headgroups. The presence of amphiphiles, such as phospholipids with unsaturated acyl chains, which destabilize the lipid bilayer, also increases liposome susceptibility to LFUS. Application of these principles to design highly LFUS-responsive liposomes is discussed.

Simple Detection of Large InDeLS by DHPLC: The ACE Gene as a Model

Directory of Open Access Journals (Sweden)

Renata Guedes Koyama

2008-01-01

Full Text Available Insertion-deletion polymorphism (InDeL is the second most frequent type of genetic variation in the human genome. For the detection of large InDeLs, researchers usually resort to either PCR gel analysis or RFLP, but these are time consuming and dependent on human interpretation. Therefore, a more efficient method for genotyping this kind of genetic variation is needed. In this report, we describe a method that can detect large InDeLs by DHPLC (denaturating high-performance liquid chromatography using the angiotensin-converting enzyme (ACE gene I/D polymorphism as a model. The InDeL targeted in this study is characterized by a 288 bp Alu element insertion (I. We used DHPLC at nondenaturating conditions to analyze the PCR product with a flow through the chromatographic column under two different gradients based on the differences between D and I sequences. The analysis described is quick and easy, making this technique a suitable and efficient means for DHPLC users to screen InDeLs in genetic epidemiological studies.

Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

Directory of Open Access Journals (Sweden)

Chen Z

2016-03-01

Full Text Available Zhongjian Chen,1,* Tianpeng Zhang,2,* Baojian Wu,2 Xingwang Zhang2 1Department of Pharmaceutics, Shanghai Dermatology Hospital, 2Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Malignant melanoma (MM represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs for hypoxia-inducible factor-1α (HIF-1α small interfering (siRNA delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM. Keywords: malignant melanoma, HIF-1α siRNA, chitosan, cationic liposomes, gene therapy

[Separate factors influencing the interaction of carbohydrate- containing liposomes with galactose-specific lectins].

Science.gov (United States)

Dvorkin, V M; Vidershaĭn, G Ia

1984-11-01

Some natural (Gal-Cer, Lac-Cer, desyalylated gangliosides) and synthetic (HMGal) glycolipids differing in the length of the bridge linking the terminal galactose with the hydrophobic moiety were incorporated into the liposome membranes. The precipitation of the thus obtained vesicles induced by galactose-specific lectin RCA was studied. It was shown that when the amount of the glycolipids used for the incorporation into the liposomes (1 mol. %) was the same, the vesicles with HMGal or Gal-Cer incorporated into them did not precipitate in the presence of lectin, whereas the liposomes with incorporated Lac-Cer or desyalylated gangliosides did precipitate. It was thus concluded that in order for galactose-containing liposomes precipitation by lectin RCA1 to be induced, galactose should be separated from the liposome membrane with a distance not less than 7 A. The nature of lectin-induced nonspecific precipitation of ganglioside-containing liposomes, ganglioside mycelles and cardiolipin-lecithine liposomes containing lactosylceramide was investigated. Some nonspecific ionic interactions of negatively charged liposomes and ganglioside mycelles with lectin were observed, which disappeared with a rise in the NaCl concentration up to 150-200 mM.

QPS upgrade and machine protection during LS1

International Nuclear Information System (INIS)

Denz, R.

2012-01-01

The presentation will explain all the proposed changes and discuss the impact on other shutdown activities. The upgrade of the LHC Quench Protection System QPS during LS1 with respect to radiation to electronics will concern the re-location of equipment and installation of new radiation tolerant hardware. The mid-term plan for further R2E upgrades will be addressed. The protection systems for insertion region magnets and inner triplets will be equipped with a dedicated bus-bar splice supervision including some additional modifications in order to improve the EMC immunity. The extension of the supervision capabilities of the QPS will concern the quench heater circuits, the earth voltage feelers and some tools to ease the system maintenance. The protection of the undulators will be revised in order to allow more transparent operation. The installation of snubber capacitors and arc chambers for the main quad circuits will complete the upgrade of the energy extraction systems. Finally the re-commissioning of the protection systems prior to the powering tests will be addressed. (author)

LS1 Report: PS Booster prepares for beam

CERN Multimedia

Katarina Anthony

2014-01-01

With Linac2 already up and running, the countdown to beam in the LHC has begun! The next in line is the PS Booster, which will close up shop to engineers early next week. The injector will be handed over to the Operations Group who are tasked with getting it ready for active duty.   Taken as we approach the end of LS1 activities, this image shows where protons will soon be injected from Linac2 into the four PS Booster rings. Over the coming two months, the Operations Group will be putting the Booster's new elements through their paces. "Because of the wide range of upgrades and repairs carried out in the Booster, we have a very full schedule of tests planned for the machine," says Bettina Mikulec, PS Booster Engineer in Charge. "We will begin with cold checks; these are a wide range of tests carried out without beam, including system tests with power on/off and with varying settings, as well as verification of the controls system and timings." Amon...

Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody VRC01LS: A Phase 1 open-label clinical trial in healthy adults

OpenAIRE

Gaudinski, Martin R.; Coates, Emily E.; Houser, Katherine V.; Chen, Grace L.; Yamshchikov, Galina; Saunders, Jamie G.; Holman, LaSonji A.; Gordon, Ingelise; Plummer, Sarah; Hendel, Cynthia S.; Conan-Cibotti, Michelle; Lorenzo, Margarita Gomez; Sitar, Sandra; Carlton, Kevin; Laurencot, Carolyn

2018-01-01

Background VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb) against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial. VRC01LS is a modified version of VRC01, designed for extended serum half-life by increased binding affinity to the neonatal Fc receptor. Methods and findings This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was conducted by the Vaccin...

A targeting drug-delivery model via interactions among cells and liposomes under ultrasonic excitation

International Nuclear Information System (INIS)

Xi Xiaoyu; Zhang Dong; Yang Fang; Gu Ning; Chen Di; Wu Junru; Luo Yi

2008-01-01

In our previous work, it was found that acoustic cavitation might play a role in improving the cell permeability to microparticles when liposomes were used in an in vitro experiment. The purpose of this project is to expand our study and to learn other possible mechanisms by which cells may interact with liposomes under ultrasound (US) excitation and become transiently permeable to microparticles. It is further hypothesized that two possible scenarios may be involved in in vitro experiments: (1) drug-carrying liposomes transiently overcome the cell membrane barrier and enter into a cell while the cell is still viable; (2) the liposomes incorporate with a cell at its membrane through a fusing process. To prove this hypothesis, liposomes of two different structures were synthesized: one has fluorescent molecules encapsulated into liposomes and the other has fluorescent markers incorporated into the shells of liposomes. Liposomes of each kind were mixed with human breast cancer cells (MCF7-cell line) in a suspension at 5 (liposomes) : 1 (cell) ratio and were then exposed to a focused 1 MHz ultrasound beam at its focal region for 40 s. The US signal contained 20 cycles per tone-burst at a pulse-repetition-frequency of 10 kHz; the spatial peak acoustic pressure amplitude was 0.25 MPa. It was found that the possible mechanisms might include the acoustic cavitation, the endocytosis and cell-fusion. Acoustic radiation force might make liposomes collide with cells effectively and facilitate the delivery process

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

Science.gov (United States)

Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

2010-01-01

The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

LS1 Report: on the home straight in 2014

CERN Multimedia

Anaïs Schaeffer

2013-01-01

At 7.24 a.m. on 14 February 2013 the last beams for physics were absorbed into the LHC, marking the end of Run 1. The achievements since then over the first ten months of LS1 have been remarkable. The excellent progress of the maintenance work on CERN's accelerators, which is overwhelmingly on schedule – and even ahead of schedule in some cases! – was praised by the CERN Council last week.   That being said, there is still a long way to go before the LHC re-start, with many challenges and potential pitfalls to be overcome. An overview of what still lies ahead: For the injectors (Linac 2, PS booster, LEIR, PS and AD), 2014 will begin with the recommissioning of all the access systems (scheduled for mid-February). The first power tests (to check the magnets and the power converters) will follow hot on its heels, starting in early April in the case of the PS booster. The final power tests of the injectors will be carried out at the Antiproton Decelerator in June. Th...

Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

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Yu-Fu Hung

2015-07-01

Full Text Available Dengue virus (DENV is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A is a vital component of the viral replication complex (RC and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48 is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48 to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48 to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A.

Biomolecular Interactions of Tannin Isolated from Oenothera gigas with Liposomes.

Science.gov (United States)

Sekowski, Szymon; Ionov, Maksim; Dubis, Alina; Mavlyanov, Saidmukhtar; Bryszewska, Maria; Zamaraeva, Maria

2016-04-01

We have examined the interaction between hydrolysable tannin 1-O-galloyl-4,6-hexahydroxydiphenoyl-β-D-glucose (OGβDG) with neutral liposomes as a model of cell membranes composed of three lipids: lecithin, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at different mass ratios. OGβDG in the concentration range 0.5-15 µg/ml (0.4-12 µM) strongly interacts with liposomal membranes by changing their structure, surface charge and fluidity. Used OGβDG molecules decrease and increase the rigidity of hydrophilic surface and hydrophobic parts of liposomes, respectively. At higher concentrations of tannin (>15 µM), liposomes are aggregated. Fourier Transform Infra-Red (FTIR) analysis showed that mainly -OH groups from OGβDG and also PO(2-) groups from phospholipids are responsible for the interaction. Obtained data indicate the importance of membrane lipid composition in interactions between tannins and cells.

Resposta da soja (Glycine max (L. Merrill à ação de bioestimulante = Soybean (Glycine max (L. Merrill response to biostimulant action

Directory of Open Access Journals (Sweden)

Celestina Alflen Klahold

2006-04-01

Full Text Available Objetivando verificar o efeito do bioestimulante, Stimulate®, aplicado via semente e pulverização foliar, na cultura da soja, conduziu-se um experimento sob ambiente protegido, em vasos. O delineamento foi de blocos casualizados, com 4 repetições. Os tratamentos constaram da combinação de doses de bioestimulate, aplicadas via semente (0, 3 e 5 mL kg-1 de sementes na semeadura e via foliar (0,0; 0,075; 0,150 e 0,225 mL L-1, aos 58 dias após a emergência (DAE. Realizaram-se coletas de plantas aos 73 e 129 DAE.Para algumas das variáveis estudadas, nas doses utilizadas, houve efeito negativo na resposta à aplicação de bioestimulante, para algumas doses testadas. Respostas positivas foram verificadas para massa seca de flores, raízes, razão raiz/parte aérea, número de flores, vagens e grãos e produção por planta. Destacaram-se positivamente os tratamentos: 0,0 mL 0,5 kg-1 (AS + 0,150 mL L-1 (APF; 3,0 mL 0,5 kg-1 (AS + 0,0 mL L-1 (APF; 3,0 mL 0,5 kg-1 (AS+ 0,225 mL L-1 (APF e 5,0 mL 0,5 kg-1 (AS + 0,075 mL L-1 (APF.Aiming to verify the effect of the bioestimulant, Stimulate®, applied saw by seed and leaf pulverization, in the culture of the soybean. It behaved an experiment under greenhouse, in vases. Randomized block experimental design was used, with four repetitions. The treatments consisted of the combination of bioestimulant doses: seed application (SA (0; 3; and 5 mL kg-1 of seeds in the sowing and leaf spray (LS (0.0; 0.075; 0.150; and 0.225 mL L- 1, to the 58 days after the emergency (DAE. Collections of plants were accomplished to the 73 and 129 DAE. For some of the studied variables, in the used doses, there was negative effect in the response of the biostimulant application, for some tested doses. Positives responses were verified for flowers and roots dry mass; root/shoot relation; flowers; beans and grains number; and yield for plant. They stood out the treatments: 0,0 mL 0.5 kg-1 (SA + 0.150 mL L-1 (LS; 3.0 mL 0.5 kg

Bleomycin-Loaded pH-Sensitive Polymer–Lipid-Incorporated Liposomes for Cancer Chemotherapy

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Eiji Yuba

2018-01-01

Full Text Available Cancer chemotherapeutic systems with high antitumor effects and less adverse effects are eagerly desired. Here, a pH-sensitive delivery system for bleomycin (BLM was developed using egg yolk phosphatidylcholine liposomes modified with poly(ethylene glycol-lipid (PEG-PE for long circulation in the bloodstream and 2-carboxycyclohexane-1-carboxylated polyglycidol-having distearoyl phosphatidylethanolamine (CHexPG-PE for pH sensitization. The PEG-PE/CHexPG-PE-introduced liposomes showed content release responding to pH decrease and were taken up by tumor cells at a rate 2.5 times higher than that of liposomes without CHexPG-PE. BLM-loaded PEG-PE/CHexPG-PE-introduced liposomes exhibited comparable cytotoxicity with that of the free drug. Intravenous administration of these liposomes suppressed tumor growth more effectively in tumor-bearing mice than did the free drug and liposomes without CHexPG-PE. However, at a high dosage of BLM, these liposomes showed severe toxicity to the spleen, liver, and lungs, indicating the trapping of liposomes by mononuclear phagocyte systems, probably because of recognition of the carboxylates on the liposomes. An increase in PEG molecular weight on the liposome surface significantly decreased toxicity to the liver and spleen, although toxicity to the lungs remained. Further improvements such as the optimization of PEG density and lipid composition and the introduction of targeting ligands to the liposomes are required to increase therapeutic effects and to reduce adverse effects.

Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

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Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

2015-11-01

Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

Liposomal drug delivery system from laboratory to clinic

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Kshirsagar N

2005-01-01

Full Text Available The main objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action and to achieve greater efficacy and minimise the toxic effects compared to conventional drugs. Amongst various carrier systems, liposomes have generated a great interest because of their versatility. Liposomes are vesicular concentric bilayered structures, which are biocompatible, biodegradable and nonimmumnogenic. They can control the delivery of drugs by targeting the drug to the site of action or by site avoidance drug delivery or by prolonged circulation of drugs. Amphotericin B (Amp B remains the drug of choice in most systemic mycoses and also as a second line treatment for Kala azar. However, its toxic effects often limit its use. Although the liposome delivery system has been tried for several drugs, only a few have been used in patients due to the slow development of necessary large-scale pharmaceutical procedures. This paper reviews the development of the technique for liposomal Amphotericin B (L-Amp-LRC-1, FungisomeTM drug delivery system in our laboratory in collaboration with the department of Biochemistry, Delhi University in India and proving the safety and efficacy of this preparation in clinical practice. It also attempts to compare the efficacy and benefits of our product for Indian patients with those of similar products and it includes facts from the publications that flowed from our work. As compared to conventional Amp B, Fungisome is infused over a much shorter period requiring a smaller volume and no premedication. It was found to be safe in patients who had developed serious unacceptable toxicity with conventional Amp B. In renal transplant patients, Fungisome did not produce any nephrotoxicity. Fungisome is effective in fungal infections resistant to fluconazole, conventional Amp B and in virgin and resistant cases of visceral leishmaniasis. The cost of any drug is of great significance, especially in India

Phospholipid liposomes functionalized by protein

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Glukhova, O. E.; Savostyanov, G. V.; Grishina, O. A.

2015-03-01

Finding new ways to deliver neurotrophic drugs to the brain in newborns is one of the contemporary problems of medicine and pharmaceutical industry. Modern researches in this field indicate the promising prospects of supramolecular transport systems for targeted drug delivery to the brain which can overcome the blood-brain barrier (BBB). Thus, the solution of this problem is actual not only for medicine, but also for society as a whole because it determines the health of future generations. Phospholipid liposomes due to combination of lipo- and hydrophilic properties are considered as the main future objects in medicine for drug delivery through the BBB as well as increasing their bioavailability and toxicity. Liposomes functionalized by various proteins were used as transport systems for ease of liposomes use. Designing of modification oligosaccharide of liposomes surface is promising in the last decade because it enables the delivery of liposomes to specific receptor of human cells by selecting ligand and it is widely used in pharmacology for the treatment of several diseases. The purpose of this work is creation of a coarse-grained model of bilayer of phospholipid liposomes, functionalized by specific to the structural elements of the BBB proteins, as well as prediction of the most favorable orientation and position of the molecules in the generated complex by methods of molecular docking for the formation of the structure. Investigation of activity of the ligand molecule to protein receptor of human cells by the methods of molecular dynamics was carried out.

The X3LYP extended density functional for accurate descriptions of nonbond interactions, spin states, and thermochemical properties

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Xu, Xin; Goddard, William A.

2004-01-01

We derive the form for an exact exchange energy density for a density decaying with Gaussian-like behavior at long range. Based on this, we develop the X3LYP (extended hybrid functional combined with Lee–Yang–Parr correlation functional) extended functional for density functional theory to significantly improve the accuracy for hydrogen-bonded and van der Waals complexes while also improving the accuracy in heats of formation, ionization potentials, electron affinities, and total atomic energies [over the most popular and accurate method, B3LYP (Becke three-parameter hybrid functional combined with Lee–Yang–Parr correlation functional)]. X3LYP also leads to a good description of dipole moments, polarizabilities, and accurate excitation energies from s to d orbitals for transition metal atoms and ions. We suggest that X3LYP will be useful for predicting ligand binding in proteins and DNA. PMID:14981235

The role of cavitation in liposome formation.

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Richardson, Eric S; Pitt, William G; Woodbury, Dixon J

2007-12-15

Liposome size is a vital parameter of many quantitative biophysical studies. Sonication, or exposure to ultrasound, is used widely to manufacture artificial liposomes, yet little is known about the mechanism by which liposomes are affected by ultrasound. Cavitation, or the oscillation of small gas bubbles in a pressure-varying field, has been shown to be responsible for many biophysical effects of ultrasound on cells. In this study, we correlate the presence and type of cavitation with a decrease in liposome size. Aqueous lipid suspensions surrounding a hydrophone were exposed to various intensities of ultrasound and hydrostatic pressures before measuring their size distribution with dynamic light scattering. As expected, increasing ultrasound intensity at atmospheric pressure decreased the average liposome diameter. The presence of collapse cavitation was manifested in the acoustic spectrum at high ultrasonic intensities. Increasing hydrostatic pressure was shown to inhibit the presence of collapse cavitation. Collapse cavitation, however, did not correlate with decreases in liposome size, as changes in size still occurred when collapse cavitation was inhibited either by lowering ultrasound intensity or by increasing static pressure. We propose a mechanism whereby stable cavitation, another type of cavitation present in sound fields, causes fluid shearing of liposomes and reduction of liposome size. A mathematical model was developed based on the Rayleigh-Plesset equation of bubble dynamics and principles of acoustic microstreaming to estimate the shear field magnitude around an oscillating bubble. This model predicts the ultrasound intensities and pressures needed to create shear fields sufficient to cause liposome size change, and correlates well with our experimental data.

Photosensitization of liposomes by porphyrins

Energy Technology Data Exchange (ETDEWEB)

Grossweiner, L I; Goyal, G C

1984-01-01

Lipid peroxidation was photosensitized in egg phosphatidylcholine (EPC) liposomes by hematoporphyrin (HP), hematoporphyrin derivative (HpD) and uroporphyrin I (Uro-I). Photosensitization by HP was type II via singlet oxygen (/sup 1/O/sub 2/) for the monomeric and dimeric states and type I for aggregated HP. Uro-I was an efficient type II /sup 1/O/sub 2/ photosensitizer. The HpD fraction enriched in the active biological component (HpD-A) was a type II /sup 1/O/sub 2/ photosensitizer at high and low concentrations. The spectral differences between HpD-A in buffer and solubilized in small EPC liposomes are attributed to a conformation change of a key dimer constituent from a folded to a planar geometry. The implications of the results for the action mechanism in photoradiation therapy of tumors with these porphyrins are discussed. 73 references, 1 figure, 5 tables.

Fluorescence study on the interaction of human serum albumin with Butein in liposomes