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Journal of Drug Targeting

Keren Turjeman, Yechezkel Barenholz
BACKGROUND: Steroids are the most efficacious anti-inflammatory agents. However, their toxicities and side-effects compromise their clinical application. Various strategies and major efforts were dedicated for formulating viable liposomal glucocorticosteroids (GCs), so far none of these were approved. OBJECTIVES: To evaluate these approaches for formulating GC-delivery systems, especially liposomes, and with focus on the Barenholz Lab experience. METHODS: We developed PEGylated nano-liposomes (NSSL) remotely loaded with water-soluble amphipathic weak acid GC-prodrugs...
October 18, 2016: Journal of Drug Targeting
Min Ren, Ying Wang, Xiaodong Wu, Suxia Ge, Benzhong Wang
OBJECTIVE: The study aimed to investigate the effects of combination treatment of curcumin and β-interferon (IFN-β)/retinoic acid (RA) on breast cancer cells, including cell viability, apoptosis and migration, and to determine the mechanisms related to GRIM-19 through STAT3-dependent and STAT3-independent pathways. METHODS: The following groups were used for the in vitro experiment: control siRNA, GRIM-19 siRNA, IFN-β/RA and IFN-β/RA + curcumin. Cell viability is by the MTT method, cell apoptosis by flow cytometry and cell migration by wound healing experiment; GRIM-19, STAT3, survivin, Bcl-2, GADD153 and COX-2 expression was measured by Western blot...
October 16, 2016: Journal of Drug Targeting
David Needham, Amina Arslanagic, Kasper Glud, Pablo Hervella, Leena Karimi, Poul-Flemming Høeilund-Carlsen, Koji Kinoshita, Jan Mollenhauer, Elisa Parra, Anders Utoft, Prasad Walke
The story starts in Basel at CLINAM in 2013, when I asked Pieter about making nanoparticles and he advised me to "try this solvent-exchange method we have developed for making limit sized particles". We are particularly interested in what are "limit size materials" because we want to test the feasibility of an idea: could we design, make, develop, and test the concept for treating metastatic cancer by, "Putting the Drug in the Cancer's Food? "Limit size" is the size of the cancer's food, ? the common Low Density Lipoprotein, (LDL) ~20 nm diameter...
October 16, 2016: Journal of Drug Targeting
Weipeng Zhang, Xiaowei Zheng, Ti Meng, Haisheng You, Yalin Dong, Jianfeng Xing, Chen Siying
Patient SE translation (SET) is a carcinogen in facilitating cellular growth and proliferation, and promoting tumorigenesis and metastasis. The present study was to investigate the resistance mechanisms associated with SET in paclitaxel-induced human breast cancer cells. The different expressions of SET, ATP-binding cassette (ABC) transporters and PI3K/Akt pathway between paclitaxel sensitive MCF-7/S and paclitaxel resistant MCF-7/PTX cells were identified using Western blotting. We adopted plasmid transfection to upregulate SET in MCF-7/S cells and a novel SET antagonist COG112 to decrease SET in MCF-7/PTX cells...
October 10, 2016: Journal of Drug Targeting
Nazanin Rahmanian, Morteza Eskandani, Jaleh Barar, Yadollah Omidi
Rapid progresses in nanotechnology fields have led us to use a number of advanced nanomaterials (NMs) for engineering smart multifunctional nanoparticles (NPs)/nanosystems (NSs) for targeted diagnosis and therapy of various diseases including different types of malignancies. For the effective therapy of any type of solid tumor, the treatment modality should ideally solely target the aberrant cancerous cells/tissue with no/trivial impacts on the healthy cells. One approach to achieve such unprecedented impacts can be fulfilled through the use of seamless multimodal NPs/NSs with photoacoustic properties that can be achieved using advanced NMs such as graphene oxide (GO)...
October 6, 2016: Journal of Drug Targeting
Chang Liu, Sen Yao, Xuqian Li, Feng Wang, Yanyan Jiang
iRGD (internalizing RGD) with high affinity to αν integrins was reported to enhance tumor penetrability by binding to neuropilin-1 (NRP-1). Based on our previous study, chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs), loaded with carmustine (BCNU) and its sensitizer (O(6)-benzylguanine, BG) showed stronger anti-tumor effect than free drugs. In present study, PLGA/CS NPs (NPs) with core-shell structure were prepared and modified with iRGD or mPEG. F98, C6 or U87 cell lines with different receptors levels were selected for in vitro and in vivo studies...
October 6, 2016: Journal of Drug Targeting
Victor Fattori, Karla G G Serafim, Ana C Zarpelon, Sergio M Borghi, Felipe A Pinho-Ribeiro, José C Alves-Filho, Thiago M Cunha, Fernando Q Cunha, Rúbia Casagrande, Waldiceu A Verri
The present study investigated whether endothelin-1 acts via ETA or ETB receptors to mediate superoxide anion-induced pain and inflammation. Mice were treated with clazosentan (ETA receptor antagonist) or BQ-788 (ETB receptor antagonist) prior to stimulation with the superoxide anion donor, KO2. Intraplantar treatment with 30 nmol of clazosentan or BQ-788 reduced mechanical hyperalgesia (47% and 42%), thermal hyperalgesia (68% and 76%), oedema (50% and 30%); myeloperoxidase activity (64% and 32%), and overt-pain like behaviours, such as paw flinching (42% and 42%) and paw licking (38% and 62%), respectively...
October 5, 2016: Journal of Drug Targeting
Kevin Ita
With the increasing proportion of the global geriatric population, it becomes obvious that neurodegenerative diseases will become more widespread. From an epidemiological standpoint, it is necessary to develop new therapeutic agents for the management of Alzheimer's disease, Parkinson's disease, multiple sclerosis and other neurodegenerative disorders. An important approach in this regard involves the use of the transdermal route. With transdermal drug delivery systems, it is possible to modulate the pharmacokinetic profiles of these medications and improve patient compliance...
October 5, 2016: Journal of Drug Targeting
Yimu Li, Hui Zhang, Guangxi Zhai
Recent years, docetaxel(DTX)-loaded intelligent polymeric micelles have been regarded as a promising vehicle for DTX for the reason that compared with conventional DTX loaded micelles, DTX loaded intelligent micelles not only preserve the basic functions of micelles such as DTX solubilization, enhanced accumulation in tumor tissue, and improved bioavailability and biocompatibility of DTX, but also possess other new properties, for instance, tumor specific DTX delivery and series of responses to endogenous or exogenous stimulations...
October 5, 2016: Journal of Drug Targeting
Azam Roohi, Mohammad Hojjat-Farsangi
Targeted-based cancer therapy (TBCT) or personalized medicine is one of the main treatment modalities for cancer that has been developed to decrease the undesirable effects of chemotherapy. Targeted therapy inhibits the growth of tumor cells by interrupting with particular molecules required for tumorigenesis and proliferation of tumor cells rather than interfering with dividing normal cells. Therefore, targeted therapies are anticipated to be more efficient than former tumor treatment agents with minimal side effects on non-tumor cells...
October 3, 2016: Journal of Drug Targeting
Wanting Zou, Can Sarisozen, Vladimir P Torchilin
In this study, a transferrin (Tf)-modified polyethylene glycol-phosphatidyl ethanolamine (PEG-PE)-based micellar delivery system containing paclitaxel (PTX) and tariquidar (TRQ), a potent third generation P-gp inhibitor, was prepared. The nanoformulation was evaluated by targeting efficiency, cellular association, cellular internalization pathway and cytotoxicity for reversal of PTX resistance on two multidrug resistant (MDR) ovarian carcinoma cell lines, SKOV-3TR and A2780-Adr. PTX and TRQ are both hydrophobic compounds...
October 3, 2016: Journal of Drug Targeting
Xiaowei Tai, Yang Wang, Li Zhang, Yuting Yang, Kairong Shi, Shaobo Ruan, Yayuan Liu, Huile Gao, Zhirong Zhang, Qin He
Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect...
October 2, 2016: Journal of Drug Targeting
Saghir Akhtar
No abstract text is available yet for this article.
September 27, 2016: Journal of Drug Targeting
Weihua Zhang, Jun Lin, Peng Wang, Jian Sun
Non-small cell lung cancer (NSCLC) is the major cause of lung cancer-related deaths. Erlotinib is an effective drug for NSCLC patients, but its effect in advanced NSCLC is compromised because of the drug resistance. The mechanism of erlotinib resistance in NSCLC is largely unknown. In the current study, we found that erlotinib treatment down-regulated miR-17-5p level in A549 cells and miR-17-5p was lower in acquired erlotinib-resistant A549 cells (A549-ER) compared with erlotinib-sensitive A549 cells. Consistently, miR-17-5p was down-regulated in the tumor tissues and the plasma of erlotinib-resistant NSCLC patients in comparison to those who are sensitive to erlotinib...
September 16, 2016: Journal of Drug Targeting
Jenifer Thewalt, D Peter Tieleman
We are on the cusp of a new era in therapeutics which will be characterized by drugs that can be individually tailored to a patient to be more effective and less likely to cause side effects. One of the most successful ways to deliver such drugs to the physiological site of interest involves embedding them in lipid nanoparticles. Here we give a brief history of the development of lipid-based drug carriers, emphasizing the role that biophysical characterization played in their development. We further argue that in the future, the revolutionary gain in power of computer simulation techniques will enable researchers to efficiently identify optimal lipid nanoparticle compositions and physical characteristics for experimental validation...
September 8, 2016: Journal of Drug Targeting
Matthew Tiffany, Francis C Szoka
We utilized quantitative high-resolution single particle tracking to study the internalization and endosomal sorting of lipid nanoparticles (LNPs) by HeLa cells in vitro to gain a better understanding of how cells process LNPs that are used for siRNA delivery. We compared the trafficking of three formulations that have been demonstrated to deliver siRNA into cells. They were composed of either: a tritratable anionic lipid, formulation of cholesterol hemisuccinate (CHEMS), or a titratatable cationic lipid formulation of, 1,2-dilinoleyloxy-3- dimethylaminopropane (DLinDMA), or a non-titratable cationic formulation lipid formulation of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)...
September 7, 2016: Journal of Drug Targeting
Daisuke Kano, Yoshihiro Nakagami, Hiroaki Kurihara, Shota Hosokawa, Sadamoto Zenda, Masahiko Kusumoto, Hirofumi Fujii, Tomohiro Kaneta, Shinichiro Saito, Yoshihiro Uesawa, Hajime Kagaya
In vivo biodistribution of small interfering RNAs (siRNAs) is important to develop them for medical use. Therefore, novel single photon emitter-labelled siRNA was prepared by using diethylenetriamine-N,N,N',N″,N″-pentaacetic acid (DTPA) and poly(A) polymerase, and subsequently, real-time analysis of siRNA trafficking was performed by using single photon emission computed tomography (SPECT). This study aimed at assessing the use of (99m)Tc-radiolabelled siRNA targeting lacZ to detect lacZ expression in vivo...
September 2, 2016: Journal of Drug Targeting
Ying K Tam, Thomas D Madden, Michael J Hope
For the best part of 40 years, lipids and membrane fusion have been at the center of Pieter's research. Projects range from the purely academic quest of understanding the roles of lipids in biological membranes, to the translation of this knowledge into the most advanced lipid nanoparticle (LNP) drug delivery systems in clinical trials to-date. Pieter's pioneering work in lipid polymorphism and characterizing the unique properties of unsaturated phospatidyethanolamines (PE), together with the introduction of ionizable, dialkylamino lipids to trigger membrane fusion at acidic pH, provided the foundation on which a new generation of highly potent, well-tolerated LNPs for intravenous delivery of nucleic acid therapeutics has been built...
September 2, 2016: Journal of Drug Targeting
Rachel Huey, Susan Hawthorne
Rabies virus glycoprotein (RVG), a 505 amino acid type-1 glycoprotein, is responsible for the neurotrophic nature of the rabies virus infection. Despite varying reports in the literature as to which receptor is ultimately responsible for interaction of RVG with the nervous system, there is a strong argument for major nicotinic acetylcholine receptor (nAChR) involvement. Peptide derivatives of RVG, such as rabies virus-derived peptide (RDP) and RVG-29 are emerging as promising targeting ligands for the delivery of therapeutics to the central nervous system (CNS)...
August 31, 2016: Journal of Drug Targeting
Chenyu Yan, Chengqun Chen, Lin Hou, Huijuan Zhang, Yingyu Che, Yuedong Qi, Xiaojian Zhang, Jingliang Cheng, Zhenzhong Zhang
An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be loaded with the anticancer drug doxorubicin (DOX) and magnetic resonance imaging (MRI) contrast agent Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). This DOX and Gd-DTPA loaded NGR functionalized SWCNTs (DOX/NGR-SWCNTs/Gd-DPTA) retained both cytotoxicity of DOX and MRI contrast effect of Gd-DPTA. This drug delivery system showed excellent stability in physiological solutions...
August 8, 2016: Journal of Drug Targeting
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