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Journal of Drug Targeting

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https://www.readbyqxmd.com/read/28817988/interferon-dimers-ifn-peg-ifn
#1
Annabelle Herrington-Symes, Ji-Won Choi, Steve Brocchini
Increasingly complex proteins can be made by a recombinant chemical approach where proteins that can be made easily can be combined by site-specific chemical conjugation to form multifunctional or more active protein therapeutics. Protein dimers may display increased avidity for cell surface receptors. The increased size of protein dimers may also increase circulation times. Cytokines bind to cell surface receptors that dimerise, so much of the solvent accessible surface of a cytokine is involved in binding to its target...
August 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28817973/the-agma1-polyamidoamine-mediates-the-efficient-delivery-of-sirna
#2
Roberta Cavalli, Luca Primo, Roberto Sessa, Giulia Chiaverina, Laura di Blasio, Jenny Alongi, Amedea Manfredi, Elisabetta Ranucci, Paolo Ferruti
AGMA1, a prevailingly cationic, guanidine-bearing, linear, amphoteric polyamidoamine is an effective siRNA condensing agent. Here two AGMA1 samples of different molecular weight, i.e. AGMA1-5 and AGMA1-10 were evaluated as siRNA condensing agents and transfection promoters. AGMA1-10 formed stable polyplexes with a size lower than 50 nm and positive zeta potential. AGMA1-5 polyplexes were larger, about 100 nm in size. AGMA1-10 polyplexes, but not AGMA1-5 proved to be an effective intracellular siRNA carrier, able to trigger gene silencing in Hela and PC3 cell lines without eliciting cytotoxic effects...
August 18, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812391/ph-sensitive-polymersomes-controlling-swelling-via-copolymer-structure-and-chemical-composition
#3
Simone Villani, Renata Adami, Ernesto Reverchon, Anna Maria Ferretti, Alessandro Ponti, Marilena Lepretti, Ivana Caputo, Lorella Izzo
pH-sensitive vesicles used as drug delivery systems (DDSs) are generally composed of protonable copolymers. The disaggregation of these nanoparticles (NPs) during drug release implies the dispersion of positively charged cytotoxic polyelectrolytes in the human body. To alleviate such issue, we synthesised A(BC)n amphiphilic block copolymers with linear (n = 1) and branched (n = 2) architectures to obtain pH-sensitive vesicles capable of releasing drugs in acidic conditions via controlled swelling instead of disaggregation...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28812388/silk-nanoparticles-proof-of-lysosomotropic-anticancer-drug-delivery-at-single-cell-resolution
#4
John D Totten, Thidarat Wongpinyochit, F Philipp Seib
Silk nanoparticles are expected to improve chemotherapeutic drug targeting to solid tumours by exploiting tumour pathophysiology, modifying the cellular pharmacokinetics of the payload and ultimately resulting in trafficking to lysosomes and triggering drug release. However, experimental proof for lysosomotropic drug delivery by silk nanoparticles in live cells is lacking and the importance of lysosomal pH and enzymes controlling drug release is currently unknown. Here, we demonstrate, in live single human breast cancer cells, the role of the lysosomal environment in determining silk nanoparticle-mediated drug release...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28658990/optimisation-of-peptides-that-actively-cross-the-tympanic-membrane-by-random-amino-acid-extension-a-phage-display-study
#5
Arwa Kurabi, Daniel Schaerer, Lisa Chang, Kwang Pak, Allen F Ryan
Local treatment of middle ear (ME) disease currently requires surgical penetration of the tympanic membrane (TM). We previously discovered 12-mer peptides that are actively transported across the intact TM, a process that could be used for non-invasive drug delivery into the ME. To optimise transport and provide further understanding of the peptides transport mechanism, we extended two of the candidate peptides by six additional amino acids at random, and screened the resulting 18-mers libraries on TMs of rats with active bacterial otitis media (OM) for transport efficiency using phage display...
August 16, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28805509/enhanced-cell-killing-and-apoptosis-of-oral-squamous-cell-carcinoma-cells-with-ultrasound-in-combination-with-cetuximab-coated-albumin-microbubbles
#6
Kyoichi Narihira, Akiko Watanabe, Hong Sheng, Hitomi Endo, Loreto B Feril, Yutaka Irie, Koichi Ogawa, Seyedeh Moosavi-Nejad, Seiji Kondo, Toshihiro Kikuta, Katsuro Tachibana
Targeted microbubbles has the potential to be used for ultrasound (US) therapy and diagnosis of various cancers. In the present study, US was irradiated to oral squamous cell carcinoma cells (HSC-2) in the presence of cetuximab coated albumin microbubbles (CCAM). Cell killing rate with ultrasound treatment at 0.9W/cm(2) and 1.0W/cm(2) in the presence of CCAM was greater compared to non-targeted albumin microbubbles (p < 0.05). On the other hand, selective cell killing was not observed in human myelomonocytic lymphoma cell line (U937) that had no affinity to cetuximab...
August 14, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28805469/long-chain-triglycerides-based-self-nanoemulsifying-oily-formulations-sneofs-of-darunavir-with-improved-lymphatic-targeting-potential
#7
Babita Garg, Sarwar Beg, Ranjot Kaur, Rajendra Kumar, Om Prakash Katare, Bhupinder Singh
The current studies entail systematic development of SNEOFs containing long-chain triglycerides for improving lymphatic targeting of darunavir for complete inhibition of HIV progression. As per QbD-oriented approach for formulation development, the QTPP was defined and CQAs were earmarked. Preformulation equilibrium solubility and phase diagram studies, and risk assessment through FMEA studies identified Lauroglycol 90, Tween 80 and Transcutol HP as the lipid, emulgent and cosolvent, respectively, for formulating SNEOFs of darunavir...
August 14, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28805085/strategies-to-release-doxorubicin-from-doxorubicin-delivery-vehicles
#8
Juan Li, Bin Zhang, Chunwen Yue, Jing Wu, Lanxia Zhao, Deqing Sun, Rongmei Wang
Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli...
August 13, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28805084/covalent-immobilisation-of-transglutaminase-stability-and-applications-in-protein-pegylation
#9
Antonella Grigoletto, Anna Mero, Hiroki Yoshioka, Oddone Schiavon, Gianfranco Pasut
Microbial transglutaminase enzyme (mTGase) is an extremely useful enzyme that is increasingly employed in the food and pharmaceutical industries and as a tool for protein modification and tagging. The current study describes how we immobilised mTGase (iTGase) on a solid support to improve its stability during the PEGylation process by which polyethylene glycol chains are attached to protein and peptide drugs. When the enzyme was immobilised at the N-terminal sequence on agarose beads, it retained more than 53% of its starting activity...
August 13, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28797169/general-overview-of-lipid-polymer-hybrid-nanoparticles-dendrimers-micelles-liposomes-spongosomes-and-cubosomes
#10
Rajesh R Wakaskar
In recent years, the wider use of nanotechnology has attracted greater attention from scientists in multi-disciplinary fields. Nanotechnological research has come a long way in the past decade, with major advances being made, both in terms of diagnostic as well as therapeutic potential of nanoparticles. Areas covered: Some of the prominently discussed nanoparticles in this day and age are polymeric micelles, liposomes, lipid-polymer hybrid nanoparticles, dendrimers, spongosomes and cubosomes. This review attempts to focus on the conventional advantages and exemplary features that these particles possess, thus making them some of the most ideal vehicles for drug delivery...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28796540/recent-advances-in-targeted-delivery-of-tissue-plasminogen-activator-for-enhanced-thrombolysis-in-ischemic-stroke
#11
Masumeh Zamanlu, Mehdi Farhoudi, Morteza Eskandani, Javad Mahmoudi, Jaleh Barar, Mohammad Rafi, Yadollah Omidi
Tissue plasminogen activator (tPA) is the only FDA approved medical treatment for the ischemic stroke. However, it associates with some inevitable limitations, including: short therapeutic window, extremely short half-life and low penetration in large clots. Systemic administration (i.v./i.a.) may lead to complications such as hemorrhagic conversion in the brain and relapse in the form of re-occlusion. Furthermore, ultrasound has been utilized in combination with contrast agents, echogenic liposome, microspheres or nanoparticles carrying tPA for improving thrombolysis - an approach that has resulted in slight improvement of tPA delivery and facilitated thrombolysis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795867/biophysical-studies-in-polymer-therapeutics-the-interactions-of-anionic-and-cationic-pamam-dendrimers-with-lipid-monolayers
#12
Marleen Wilde, Rebecca J Green, Michael R Sanders, Francesca Greco
Understanding how polymers interact with biological membranes is important for the development of polymer based therapeutics and wider biomedical applications. Here, biophysical methods (surface pressure measurements, external reflection FTIR) have been used to investigate the interaction between PAMAM dendrimers (Generation 5 or 4.5) and anionic (DPPG) or zwitterionic (DPPC) model membranes. We observed a concentration-dependent binding behaviour of both PAMAM species to both model membranes; however, equivalent levels of penetration into DPPC monolayers required approximately 10-fold higher dendrimer concentrations than for penetration into DPPG monolayers...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795851/selective-induction-of-apoptosis-in-mcf7-cancer-cell-by-targeted-liposomes-functionalized-with-mannose-6-phosphate
#13
Cristina Minnelli, Laura Cianfruglia, Emiliano Laudadio, Roberta Galeazzi, Michela Pisani, Emanuela Crucianelli, Davide Bizzaro, Tatiana Armeni, Giovanna Mobbili
Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalization and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795849/doxorubicin-conjugated-d-glucosamine-and-folate-bi-functionalized-inp-zns-quantum-dots-for-cancer-cells-imaging-and-therapy
#14
Zahra Ranjbar-Navazi, Morteza Eskandani, Mohammad Johari-Ahar, Ali Nemati, Hamid Akbari, Soudabeh Davaran, Yadollah Omidi
Nanoscaled quantum dots (QDs), with unique optical properties have been used for development of theranostics. Here, InP/ZnS QDs were synthesized and functionalized with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalized QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In: MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28795601/poly-glutamic-dendrimer-based-conjugates-for-cancer-vaccination-a-computational-design-for-targeted-delivery-of-antigens
#15
L I F Moura, N Martinho, L C Silva, T S Barata, S Brocchini, H F Florindo, M Zloh
Computational techniques are useful to predict interaction models and molecular properties for the design of drug delivery systems, such as dendrimers. This work evaluated the impact of surface modifications of mannosamine-conjugated multifunctional poly(glutamic acid) (PG)-dendrimers as nanocarriers of the tumour associated antigens (TAA) MART-1, gp100:44 and gp100:209. Molecular dynamics simulations and docking studies were performed. Nitrobenzoxadiazole (NBD)-PG-G4-dendrimer displayed 64 carboxylic groups, however, the Frontier Molecular Orbital Theory study evidenced that only 32 of those were available to form covalent bonds...
August 10, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28792244/a-novel-%C3%AE-v%C3%AE-3-ligand-modified-hpma-copolymers-for-anticancer-drug-delivery
#16
Fengling Wang, Lian Li, Wei Sun, Lijia Li, Yuanyuan Liu, Yuan Huang, Zhou Zhou
The integrin αVβ3 receptor emerged as one of the most promising targets owing to its high expression on the surface of various malignant tumor cells and tumor angiogenesis endothelial cells, but with little expression in mature endothelial cells and the majority of normal cells. Here we report a new targeting ligand FQSIYPpIK (FQS) with high affinity to integrin αVβ3 receptor. To take the advantage of the particular interaction between FQS and integrin αVβ3 receptor, FQS was linked to N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers...
August 9, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28783978/polymer-therapeutics-at-a-crossroads-finding-the-path-for-improved-translation-in-the-twenty-first-century
#17
Ruth Duncan
Despite the relatively small early investment, first generation 'polymer therapeutics' have been remarkably successful with more than 25 products licenced for human use as polymeric drugs, sequestrants, conjugates, and as an imaging agent. Many exhibit both clinical and commercial success with new concepts already in clinical trials. Nevertheless after four decades of evolution, this field is arriving at an important crossroads. Over the last decade, the landscape has changed rapidly. There are an increasing number of failed clinical trials, the number of 'copy' and 'generic' products is growing (danger of ignoring the biological rationale for design and suppression of innovation), potential drawbacks of PEG are becoming more evident, and the 'nanomedicine' boom has brought danger of loss of scientific focus/hype...
August 8, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28743200/green-fluorescent-protein-gfp-is-seeing-believing-and-is-that-enough
#18
Susan A Shorter, Marie W Pettit, Paul D R Dyer, J Emma Coakley-Youngs, Monique A M Gorringe-Pattrick, Samer El-Daher, Simon C W Richardson
Intracellular compartmentalisation is a significant barrier to the successful nucleocytosolic delivery of biologics. The endocytic system has been shown to be responsible for compartmentalisation, providing an entry point, and trigger(s) for the activation of drug delivery systems. Consequently, many of the technologies used to understand endocytosis have found utility within the field of drug delivery. The use of fluorescent proteins as markers denoting compartmentalisation within the endocytic system has become commonplace...
July 26, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28737432/integrin-targeted-nano-sized-polymeric-systems-for-paclitaxel-conjugation-a-comparative-study
#19
Anat Eldar-Boock, Rachel Blau, Claudia Ryppa, Hemda Baabur-Cohen, Ariel Many, María J Vicent, Felix Kratz, Joaquin Sanchis, Ronit Satchi-Fainaro
The generation of rationally-designed polymer therapeutics via the conjugation of low molecular weight anti-cancer drugs to water-soluble polymeric nanocarriers aims to improve the therapeutic index. Here, we focus on applying polymer therapeutics to target two cell compartments simultaneously - tumor cells and angiogenic endothelial cells. Comparing different polymeric backbones carrying the same therapeutic agent and targeting moiety may shed light on any correlation between the choice of polymer and the anti-cancer activity of the conjugate...
July 24, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28737429/hif-1%C3%AE-inhibition-by-diethylstilbestrol-and-its-polyacetal-conjugate-in-hypoxic-prostate-tumour-cells-insights-from-nmr-metabolomics
#20
Ana Armiñán, Luís Mendes, Joana Carrola, Julie Movellan, María J Vicent, Iola F Duarte
In this study, we have employed (1)H NMR metabolomics to assess the metabolic responses of PC3 prostate tumour cells to hypoxia and to pharmacological HIF-1α inhibition by DES or its polyacetal conjugate tert-DES. Oxygen deprivation prompted a number of changes in intracellular composition and metabolic activity, mainly reflecting upregulated glycolysis, amino acid catabolism and other compensatory mechanisms used by hypoxic cells to deal with oxidative imbalance and energy deficit. Cell treatment with a non-cytotoxic concentration of DES, under hypoxia, triggered significant changes in 17 metabolites...
July 24, 2017: Journal of Drug Targeting
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