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https://www.readbyqxmd.com/read/29243576/a-novel-polymer-lipid-hybrid-nanoparticle-for-the-improvement-of-topotecan-hydrochloride-physicochemical-properties
#1
Emanuelle Jesus Silva, Leonardo Gomes Souza, Luis Antonio Dantas Silva, Stephania Fleury Taveira, Raquel Ciffarello Guilger, Luciano Morais Liao, Luiz Henrique Keng Queiroz Junior, Mabio Joao Santana, Ricardo Neves Marreto
BACKGROUND: Topotecan (TPT) is a water-soluble derivate of camptothecin, which undergoes ring-opening hydrolysis in neutral solutions, leading to stability loss and poor cellular uptake. Lipid nanoencapsulation can improve TPT stability, and polymer-lipid hybrid nanoparticles (PLN) are interesting alternatives to improve TPT nanoencapsulation. OBJECTIVE: This study seeks to prepare complexes between the cationic TPT and the negatively charged dextran sulfate (DS) with a view of improving drug loading, chemical stability and release control...
December 14, 2017: Current Drug Delivery
https://www.readbyqxmd.com/read/29233222/understanding-membrane-active-antimicrobial-peptides
#2
Huey W Huang, Nicholas E Charron
Bacterial membranes represent an attractive target for the design of new antibiotics to combat widespread bacterial resistance to traditional inhibitor-based antibiotics. Understanding how antimicrobial peptides (AMPs) and other membrane-active agents attack membranes could facilitate the design of new, effective antimicrobials. AMPs, which are small, gene-encoded host defense proteins, offer a promising basis for the study of membrane-active antimicrobial agents. These peptides are cationic and amphipathic, spontaneously binding to bacterial membranes and inducing transmembrane permeability to small molecules...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29232147/-incorporation-of-mrna-in-lamellar-lipid-matrices-for-parenteral-administration
#3
Antje Ziller, Sara S Nogueira, Eva Huehn, Sergio S Funari, Gerald Brezesinski, Hermann Hartmann, Ugur Sahin, Heinrich Haas, Peter Langguth
Insertion of high molecular weight messenger RNA (mRNA) into lyotropic lipid phases as model systems for controlled release formulations for the mRNA was investigated. Low fractions of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as an anchor to load the mRNA into a lamellar lipid matrix. Dispersions of zwitterionic lipid in the aqueous phase in the presence of increasing fractions of mRNA and cationic lipid were prepared, and the molecular organization was investigated as a function of mRNA and cationic lipid fraction...
December 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29232144/interactions-between-surface-immobilized-antimicrobial-peptides-and-model-bacterial-cell-membranes
#4
Xiaofeng Han, Jingguo Zheng, Fengming Lin, Kenichi Kuroda, Zhan Chen
Sum frequency generation vibrational spectroscopy (SFG) was used to study surface immobilization effects on the interactions between antimicrobial peptide (AMP) cecropin P1 (CP1) and model cell membranes. While free CP1 in solution interacted with a model cell membrane composed of a phosphatidylglycerole (PG) bilayer, electrostatic interaction led to the attachment of the CP1 molecules onto the PG surface, and the hydrophobic domain in the lipid bilayer enabled the peptides to insert into the bilayer and form α-helices from random coil structures...
December 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29223825/theranostic-liposomes-as-a-bimodal-carrier-for-magnetic-resonance-imaging-contrast-agent-and-photosensitizer
#5
Paulina Skupin-Mrugalska, Lukasz Sobotta, Alicja Warowicka, Beata Wereszczynska, Tomasz Zalewski, Piotr Gierlich, Marcin Jarek, Grzegorz Nowaczyk, Marek Kempka, Jacek Gapinski, Stefan Jurga, Jadwiga Mielcarek
The present study is focused on the development of liposomes bearing gadolinium chelate (GdLip) providing two functionalities for magnetic resonance imaging (MRI) and photodynamic therapy of cancer. A lipid derivative of gadolinium(III) diethylenetriamine pentaacetic acid salt (GdDTPA1) was inserted in the liposomal membrane and served as MRI contrast agent whereas a zinc phthalocyanine (ZnPc) was used as a model photosensitizer. In addition to conventional liposomes, pegylated lipids were used for the preparation of "stealth" liposomes...
December 2, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29217581/structure-of-the-human-trpm4-ion-channel-in-a-lipid-nanodisc
#6
Henriette E Autzen, Alexander G Myasnikov, Melody G Campbell, Daniel Asarnow, David Julius, Yifan Cheng
Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage dependent manner, but unlike many other TRP channels is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3Å resolution as determined by single particle electron cryo-microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium binding site within the intracellular side of the S1-S4 domain...
December 7, 2017: Science
https://www.readbyqxmd.com/read/29217176/a-strong-adjuvant-based-on-glycol-chitosan-coated-lipid-polymer-hybrid-nanoparticles-potentiates-mucosal-immune-responses-against-the-recombinant-chlamydia-trachomatis-fusion-antigen-cth522
#7
Fabrice Rose, Jeanette Erbo Wern, Francesca Gavins, Peter Andersen, Frank Follmann, Camilla Foged
Induction of mucosal immunity with vaccines is attractive for the immunological protection against pathogen entrance directly at the site of infection. An example is infection with Chlamydia trachomatis (Ct), which is the most common sexually transmitted infection in the world, and there is an unmet medical need for an effective vaccine. A vaccine against Ct should elicit protective humoral and cell-mediated immune (CMI) responses in the genital tract mucosa. We previously designed an antibody- and CMI-inducing adjuvant based on poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles modified with the cationic surfactant dimethyldioctadecylammonium bromide and the immunopotentiator trehalose-6,6'-dibehenate...
December 4, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29215747/nanoliposomes-as-the-adjuvant-delivery-systems-in-cancer-immunotherapy
#8
REVIEW
Parvin Zamani, Amir Abbas Momtazi-Borojeni, Maryam Ebrahimi Nik, Reza Kazemi Oskuee, Amirhossein Sahebkar
Cancer immunotherapy is one of the commonly used methods in the treatment of cancer. The aim of this approach is to strengthen or restore immune function for effective diagnosis of aberrant cells antigens. For this reason, cancer specific peptides or proteins are used as antigens to induce an immune response capable of removing cancer cells. Liposomal formulations are an important carrier system frequently used for delivery of antigen because the specific properties of this component such as lipid composition, charge, size, encapsulation of antigens or adjuvants can be changed...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29215597/application-of-pharmacokinetics-modelling-to-predict-human-exposure-of-a-cationic-liposomal-subunit-antigen-vaccine-system
#9
Raj K S Badhan, Swapnil Khadke, Yvonne Perrie
The pharmacokinetics of a liposomal subunit antigen vaccine system composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and the immunostimulatory agent trehalose 6,6-dibehenate (TDB) (8:1 molar ratio) combined with the Ag85B-ESAT-6 (H1) antigen were modelled using mouse in-vivo data. Compartment modelling and physiologically based pharmacokinetics (PBPK) were used to predict the administration site (muscle) and target site (lymph) temporal concentration profiles and factors governing these...
December 7, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29213101/modulation-of-the-neisseria-gonorrhoeae-drug-efflux-conduit-mtre
#10
Giulia Tamburrino, Salomé Llabrés, Owen N Vickery, Samantha J Pitt, Ulrich Zachariae
Widespread antibiotic resistance, especially of Gram-negative bacteria, has become a severe concern for human health. Tripartite efflux pumps are one of the major contributors to resistance in Gram-negative pathogens, by efficiently expelling a broad spectrum of antibiotics from the organism. In Neisseria gonorrhoeae, one of the first bacteria for which pan-resistance has been reported, the most expressed efflux complex is MtrCDE. Here we present the electrophysiological characterisation of the outer membrane component MtrE and the membrane fusion protein MtrC, obtained by a combination of planar lipid bilayer recordings and in silico techniques...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207496/cationic-biomimetic-particles-of-polystyrene-cationic-bilayer-gramicidin-for-optimal-bactericidal-activity
#11
Gabriel R S Xavier, Ana M Carmona-Ribeiro
Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus. The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0...
December 2, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29204423/dual-coating-of-liposomes-as-encapsulating-matrix-of-antimicrobial-peptides-development-and-characterization
#12
Ahmed I Gomaa, Cynthia Martinent, Riadh Hammami, Ismail Fliss, Muriel Subirade
Antimicrobial peptides have been proposed as a potential biopreservatives in pharmaceutical research and agribusiness. However, many limitations hinder their utilization, such as their vulnerability to proteolytic digestion and their potential interaction with other food ingredients in complex food systems. One approach to overcome such problems is developing formulations entrapping and thereby protecting the antimicrobial peptides. Liposome encapsulation is a strategy that could be implemented to combine protection of the antimicrobial activity of the peptides from proteolytic enzymes and the controlled release of the encapsulated active ingredients...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29203416/quantitative-contributions-of-processes-by-which-polyanion-drugs-reduce-intracellular-bioavailability-and-transfection-efficiency-of-cationic-sirna-lipoplex
#13
Pharavee Jaiprasart, Bertrand Z Yeung, Ze Lu, M Guillaume Wientjes, Minjian Cui, Chien-Ming Hsieh, Sukyung Woo, Jessie L-S Au
RNA Interference (RNAi) is a potentially useful tool to correct the detrimental effects of faulty genes; several RNAi are undergoing clinical evaluation in various diseases. The present study identified the relative contributions of three mechanisms by which polyanion drugs reduced the gene silencing activity of Lipoplex, a complex of small interfering RNA (siRNA) and cationic liposomes. The study used a siRNA against the chemoresistance gene survivin and two model polyanion drugs (suramin, heparin). Products of Lipoplex destabilization were separated, identified, and/or quantified using ultrafiltration, gel electrophoresis, and RT-qPCR (quantitative reverse transcription polymerase chain reaction)...
December 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29198120/in-situ-interfacial-conjugation-of-chitosan-with-cinnamaldehyde-during-homogenization-improves-the-formation-and-stability-of-chitosan-stabilized-emulsions
#14
Huanle Chen, David Julian McClements, Enmin Chen, Shilin Liu, Bin Li, Yan Li
The emulsifying properties of a natural cationic polysaccharide (chitosan) were improved by in situ conjugation with a natural essential oil (cinnamaldehyde, CA) during homogenization. In the absence of CA, chitosan-coated medium chain triglyceride (MCT) droplets were highly susceptible to creaming and coalescence at pH values ranging from 1 to 6.5. However, incorporation of relatively low levels of CA in the oil phase greatly improved the formation and stability of the oil-in-water emulsions. These effects were attributed to two main factors: (i) covalent binding of lipophilic CA moieties to hydrophilic chitosan chains leading to conjugates with good surface-activity; (ii) interfacial cross-linking of adsorbed chitosan layers by CA leading to the formation of a rigid polymeric coating around the lipid droplets that improved their stability against coalescence...
December 4, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29191134/safety-evaluation-of-lipid-nanoparticle-formulated-modified-mrna-in-the-sprague-dawley-rat-and-cynomolgus-monkey
#15
Maja Sedic, Joseph J Senn, Andy Lynn, Michael Laska, Mike Smith, Stefan J Platz, Joseph Bolen, Stephen Hoge, Alex Bulychev, Eric Jacquinet, Victoria Bartlett, Peter F Smith
The pharmacology, pharmacokinetics, and safety of modified mRNA formulated in lipid nanoparticles (LNPs) were evaluated after repeat intravenous infusion to rats and monkeys. In both species, modified mRNA encoding the protein for human erythropoietin (hEPO) had predictable and consistent pharmacologic and toxicologic effects. Pharmacokinetic analysis conducted following the first dose showed that measured hEPO levels were maximal at 6 hours after the end of intravenous infusion and in excess of 100-fold the anticipated efficacious exposure (17...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/29190500/inhibition-of-intrinsic-coagulation-improves-safety-and-tumor-targeted-drug-delivery-of-cationic-solid-lipid-nanoparticles
#16
Xuan Wu, Hongmei Chen, Chenxi Wu, Jialiang Wang, Shi Zhang, Jing Gao, Hongda Wang, Tianmeng Sun, Yong-Guang Yang
Cationic solid lipid nanoparticles (cSLNs) are promising nanoparticles for controlled drug delivery. Increasing surface charge and/or reducing PEG density enhance cellular uptake of cSLNs in vitro, but for unknown reasons fail to improve drug delivery in vivo. Herein, we show that cSLNs present a risk for systemic platelet activation and aggregation in vivo, and this toxic effect can be significantly augmented by increasing the surface charge and reducing the PEG density. Furthermore, thrombotic toxicity significantly reduces blood circulation time and in vivo cellular uptake of cSLNs...
November 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/29182583/trans-double-bond-containing-liposomes-as-potential-carriers-for-drug-delivery
#17
Giorgia Giacometti, Marina Marini, Kyriakos Papadopoulos, Carla Ferreri, Chryssostomos Chatgilialoglu
The use of liposomes has been crucial for investigations in biomimetic chemical biology as a membrane model and in medicinal chemistry for drug delivery. Liposomes are made of phospholipids whose biophysical characteristics strongly depend on the type of fatty acid moiety, where natural unsaturated lipids always have the double bond geometry in the cis configuration. The influence of lipid double bond configuration had not been considered so far with respect to the competence of liposomes in delivery. We were interested in evaluating possible changes in the molecular properties induced by the conversion of the double bond from cis to trans geometry...
November 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29180820/subcutaneous-white-adipocytes-express-a-light-sensitive-signaling-pathway-mediated-via-a-melanopsin-trpc-channel-axis
#18
Katarina Ondrusova, Mohammad Fatehi, Amy Barr, Zofia Czarnecka, Wentong Long, Kunimasa Suzuki, Scott Campbell, Koenraad Philippaert, Matthew Hubert, Edward Tredget, Peter Kwan, Nicolas Touret, Martin Wabitsch, Kevin Y Lee, Peter E Light
Subcutaneous white adipose tissue (scWAT) is the major fat depot in humans and is a central player in regulating whole body metabolism. Skin exposure to UV wavelengths from sunlight is required for Vitamin D synthesis and pigmentation, although it is plausible that longer visible wavelengths that penetrate the skin may regulate scWAT function. In this regard, we discovered a novel blue light-sensitive current in human scWAT that is mediated by melanopsin coupled to transient receptor potential canonical cation channels...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29172443/membrane-crossing-and-membranotropic-activity-of-cell-penetrating-peptides-dangerous-liaisons
#19
Astrid Walrant, Sébastien Cardon, Fabienne Burlina, Sandrine Sagan
Living organisms have to maintain a stable balance in molecules and ions in the changing environment in which they are living, a process known as homeostasis. At the level of cells, the plasma membrane has a major role in homeostasis, since this hydrophobic film prevents passive diffusion of large and hydrophilic molecules between the extracellular and intracellular milieu. Living organisms have evolved with highly sophisticated transport systems to control exchanges across this barrier: import of nutrients and fuel essential for their survival; recognition of chemical or physical messengers allowing information interchanges with surrounding cells...
November 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/29162835/a-signal-amplifiable-biochip-quantifies-extracellular-vesicle-associated-rnas-for-early-cancer-detection
#20
Jiaming Hu, Yan Sheng, Kwang Joo Kwak, Junfeng Shi, Bohao Yu, L James Lee
Detection of extracellular vesicle (EV)-associated RNAs with low expression levels in early-stage cancer remains a challenge and is highly valuable. Here, we report a nanoparticle-based biochip that could capture circulating EVs without isolation, brighten encapsulated RNAs, and amplify fluorescence signals in situ in a single step. We confine catalyzed hairpin DNA circuit (CHDC) in cationic lipid-polymer hybrid nanoparticles (LPHNs) that are tethered on a chip. LPHN features a core-shell-corona structure that facilitates the transfer and mixing of CHDC with EV-associated RNAs when forming the LPHN-EV nanocomplex...
November 22, 2017: Nature Communications
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