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https://www.readbyqxmd.com/read/27922002/targeting-the-notch-regulated-non-coding-rna-tug1-for-glioma-treatment
#1
Keisuke Katsushima, Atsushi Natsume, Fumiharu Ohka, Keiko Shinjo, Akira Hatanaka, Norihisa Ichimura, Shinya Sato, Satoru Takahashi, Hiroshi Kimura, Yasushi Totoki, Tatsuhiro Shibata, Mitsuru Naito, Hyun Jin Kim, Kanjiro Miyata, Kazunori Kataoka, Yutaka Kondo
Targeting self-renewal is an important goal in cancer therapy and recent studies have focused on Notch signalling in the maintenance of stemness of glioma stem cells (GSCs). Understanding cancer-specific Notch regulation would improve specificity of targeting this pathway. In this study, we find that Notch1 activation in GSCs specifically induces expression of the lncRNA, TUG1. TUG1 coordinately promotes self-renewal by sponging miR-145 in the cytoplasm and recruiting polycomb to repress differentiation genes by locus-specific methylation of histone H3K27 via YY1-binding activity in the nucleus...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#2
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27921382/core-shell-silk-hydrogels-with-spatially-tuned-conformations-as-drug-delivery-system
#3
Le-Ping Yan, Joaquim M Oliveira, Ana L Oliveira, Rui L Reis
Hydrogels of spatially controlled physicochemical properties are appealing platforms for tissue engineering and drug delivery. In this study, core-shell silk fibroin (SF) hydrogels of spatially controlled conformation were developed. The core-shell structure in the hydrogels was formed by means of soaking the preformed (enzymatically crosslinked) random coil SF hydrogels in methanol. When increasing the methanol treatment time from 1 to 10 min, the thickness of the shell layer can be tuned from about 200 to about 850 μm as measured in wet status...
December 5, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27921280/ph-responsive-triblock-copolymeric-micelles-decorated-with-a-cell-penetrating-peptide-provide-efficient-doxorubicin-delivery
#4
Khen Eng Ng, Mohd Cairul Iqbal Mohd Amin, Haliza Katas, Muhammad Wahab Amjad, Adeel Masood Butt, Prashant Kesharwani, Arun K Iyer
This study developed novel triblock pH-responsive polymeric micelles (PMs) using cholic acid-polyethyleneimine-poly-L-arginine (CA-PEI-pArg) copolymers. PEI provided pH sensitivity, while the hydrophilic cell-penetrating pArg peptide promoted cellular PM internalization. The copolymers self-assembled into PMs in aqueous solution at above the critical micelle concentration (2.98 × 10(-7) M) and encapsulated doxorubicin in the core region, with a 34.2% (w/w) entrapment efficiency. PMs showed pH-dependent swelling, increasing in size by almost sevenfold from pH 7...
December 2016: Nanoscale Research Letters
https://www.readbyqxmd.com/read/27921260/development-of-oral-flexible-tablet-oft-formulation-for-pediatric-and-geriatric-patients-a-novel-age-appropriate-formulation-platform
#5
Prabagaran Chandrasekaran, Ruckmani Kandasamy
Development of palatable formulations for pediatric and geriatric patients involves various challenges. However, an innovative development with beneficial characteristics of marketed formulations in a single formulation platform was attempted. The goal of this research was to develop solid oral flexible tablets (OFTs) as a platform for pediatrics and geriatrics as oral delivery is the most convenient and widely used mode of drug administration. For this purpose, a flexible tablet formulation using cetirizine hydrochloride as model stability labile class 1 and 3 drug as per the Biopharmaceutical Classification System was developed...
December 5, 2016: AAPS PharmSciTech
https://www.readbyqxmd.com/read/27920531/in-vitro-evaluation-of-folic-acid-conjugated-redox-responsive-mesoporous-silica-nanoparticles-for-the-delivery-of-cisplatin
#6
Merlis P Alvarez-Berríos, Juan L Vivero-Escoto
The use of cisplatin(IV) prodrugs for the delivery of cisplatin have gained significant attention, because of their low toxicity and reactivity. Recent studies have shown that targeted cisplatin(IV)-prodrug nanoparticle-based delivery systems can improve the internalization of the cisplatin(IV) prodrug. We hypothesized that folic acid-conjugated mesoporous silica nanoparticles (MSNs) containing cisplatin(IV) prodrug could target cancer cells that overexpress the folate receptor and deliver the active cisplatin drug upon intracellular reduction...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920529/synthetic-high-density-lipoproteins-for-delivery-of-10-hydroxycamptothecin
#7
Yue Yuan, Jian Wen, Jie Tang, Qiming Kan, Rose Ackermann, Karl Olsen, Anna Schwendeman
The purpose of this study was to develop a novel synthetic high-density lipoprotein (sHDL) nanoparticle delivery system for 10-hydroxycamptothecin (HCPT) for treatment of colon carcinoma. HDL is recognized by scavenger receptor B-I (SR-BI) over-expressed in colon carcinomas 5- to 35-fold relative to the human fibroblasts. The sHDL nanoparticles were composed of apolipoprotein A-I mimic peptide (5A) and contained 0.5%-1.5% (w/w) of HCPT. An optimized HCPT-sHDL formulation exhibited 0.7% HCPT loading with 70% efficiency with an average size of 10-12 nm...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920520/ligand-based-targeted-therapy-a-novel-strategy-for-hepatocellular-carcinoma
#8
REVIEW
Min Li, Weiyue Zhang, Birong Wang, Yang Gao, Zifang Song, Qi Chang Zheng
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919215/current-strategies-in-modification-of-plga-based-gene-delivery-system
#9
Mohammad Ramezani, Mahboubeh Ebrahimian, Maryam Hashemi
The successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and gene efficiently. This formulation has several advantages in comparison with other formulations including improvement of solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as gene carrier, there exist many challenges. PLGA nanoparticles could protect the encapsulated DNA from in vivo degradation but the DNA release is slowl and their negative charge acts as a barrier to DNA incorporation and delivery...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27919214/hydrogel-based-drug-delivery-systems-a-review-with-special-emphasis-on-challenges-associated-with-decontamination-of-hydrogels-and-biomaterials
#10
Irene Satiko Kikuchi, Raquel Galante, Kamal Dua, Daniela Dal Molim Ghisleni, Terezinha de Jesus Andreoli Pinto, Venkata Ramana Malipeddi, Rajendra Awasthi
Many researches involving the development of new techniques and biomaterials to formulate a suitable drug delivery systems and tissue engineering have been conducted. The majority of published literature from these researches emphasizes the production and materials characterization. However there is very limited information regarding their sterilization methods. The present review article has summarized various different literatures that encompasses the difficulties encountered with sterilization methods in the preparations of hydrogels for biological applications...
December 5, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27918989/ph-responsive-polymeric-micelles-based-on-poly-ethyleneglycol-b-poly-2-diisopropylamino-ethyl-methacrylate-block-copolymer-for-enhanced-intracellular-release-of-anticancer-drugs
#11
Zhigang Xu, Peng Xue, Yong-E Gao, Shiying Liu, Xiaoxiao Shi, Meili Hou, Yuejun Kang
We present a pH-responsive poly(ethyleneglycol)-b-poly(2-(diisopropylamino) ethyl methacrylate) block copolymer (MPEG-PPDA) that can self-assemble into micelles at very low critical micelle concentration. The formed micelles exhibit superior stability in physiological environment and pH-triggered transforming capability between self-assembly and disassembly. Moreover, the resulting micelles can load hydrophobic anticancer drug molecules such as doxorubicin in the core of micelles. The pH-triggered drug release kinetics matches the classical hydrazone bond model...
November 27, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27918966/development-of-novel-cilostazol-loaded-solid-snedds-using-a-spg-membrane-emulsification-technique-physicochemical-characterization-and-in-vivo-evaluation
#12
Omer Mustapha, Kyung Soo Kim, Shumaila Shafique, Dong Shik Kim, Sung Giu Jin, Youn Gee Seo, Yu Seok Youn, Kyung Taek Oh, Beom-Jin Lee, Young Joon Park, Chul Soon Yong, Jong Oh Kim, Han-Gon Choi
The objective of this study was to develop a novel solid self-nanoemulsifying drug delivery system (SNEDDS) using a membrane emulsification technique involving Shirasu porous glass (SPG) which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution and oral bioavailability of poorly water-soluble cilostazol. The effects of carriers on the drug solubility were assessed, and pseudo-ternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of peceol (oil), Tween 20 (surfactant) and Labrasol (cosurfactant) at a weight ratio of 15/55/30, produced the smallest emulsion droplet size...
November 29, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27918885/mutant-ccl2-protein-coating-mitigates-wear-particle-induced-bone-loss-in-a-murine-continuous-polyethylene-infusion-model
#13
Akira Nabeshima, Jukka Pajarinen, Tzu-Hua Lin, Xinyi Jiang, Emmanuel Gibon, Luis A Córdova, Florence Loi, Laura Lu, Eemeli Jämsen, Kensuke Egashira, Fan Yang, Zhenyu Yao, Stuart B Goodman
Wear particle-induced osteolysis limits the long-term survivorship of total joint replacement (TJR). Monocyte/macrophages are the key cells of this adverse reaction. Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) is the most important chemokine regulating trafficking of monocyte/macrophages in particle-induced inflammation. 7ND recombinant protein is a mutant of CCL2 that inhibits CCL2 signaling. We have recently developed a layer-by-layer (LBL) coating platform on implant surfaces that can release biologically active 7ND...
November 24, 2016: Biomaterials
https://www.readbyqxmd.com/read/27918644/self-assembled-supramolecular-nanogels-as-a-safe-and-effective-drug-delivery-vector-for-cancer-therapy
#14
Chih-Chia Cheng, Mei-Chih Liang, Zhi-Sheng Liao, Jyun-Jie Huang, Duu-Jong Lee
Simple construction and manipulation of low-molecular-weight supramolecular nanogels, based on the introduction of multiple hydrogen bonding interactions, with the desired physical properties to achieve effective and safe delivery of drugs for cancer therapy remain highly challenging. Herein, a novel supramolecular oligomer cytosine (Cy)-polypropylene glycol containing self-complementary multiple hydrogen-bonded Cy moieties is developed, which undergoes spontaneous self-assembly to form nanosized particles in an aqueous environment...
December 5, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27918641/evaluation-of-the-biocompatibility-of-polypyrrole-implanted-subdurally-in-gaers
#15
Sebastien H Bauquier, Karen J McLean, Jonathan L Jiang, Ray C Boston, Alan Lai, Zhilian Yue, Simon E Moulton, Amy J Halliday, Gordon Wallace, Mark J Cook
This blinded controlled prospective randomized study investigates the biocompatibility of polypyrrole (PPy) polymer that will be used for intracranial triggered release of anti-epileptic drugs (AEDs). Three by three millimeters PPy are implanted subdurally in six adult female genetic absence epilepsy rats from Strasbourg. Each rat has a polymer implanted on one side of the cortex and a sham craniotomy performed on the other side. After a period of seven weeks, rats are euthanized and parallel series of coronal sections are cut throughout the implant site...
December 5, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27918558/quantitating-drug-target-engagement-in-single-cells-in-vitro-and-in-vivo
#16
J Matthew Dubach, Eunha Kim, Katherine Yang, Michael Cuccarese, Randy J Giedt, Labros G Meimetis, Claudio Vinegoni, Ralph Weissleder
Quantitation of drug target engagement in single cells has proven to be difficult, often leaving unanswered questions in the drug development process. We found that intracellular target engagement of unlabeled new therapeutics can be quantitated using polarized microscopy combined with competitive binding of matched fluorescent companion imaging probes. We quantitated the dynamics of target engagement of covalent BTK inhibitors, as well as reversible PARP inhibitors, in populations of single cells using a single companion imaging probe for each target...
December 5, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27918464/checkpoints-to-the-brain-directing-myeloid-cell-migration-to-the-central-nervous-system
#17
REVIEW
Meredith Harrison-Brown, Guo-Jun Liu, Richard Banati
Myeloid cells are a unique subset of leukocytes with a diverse array of functions within the central nervous system during health and disease. Advances in understanding of the unique properties of these cells have inspired interest in their use as delivery vehicles for therapeutic genes, proteins, and drugs, or as "assistants" in the clean-up of aggregated proteins and other molecules when existing drainage systems are no longer adequate. The trafficking of myeloid cells from the periphery to the central nervous system is subject to complex cellular and molecular controls with several 'checkpoints' from the blood to their destination in the brain parenchyma...
December 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27918445/docetaxel-loaded-self-assembly-stearic-acid-modified-bletilla-striata-polysaccharide-micelles-and-their-anticancer-effect-preparation-characterization-cellular-uptake-and-in-vitro-evaluation
#18
Qingxiang Guan, Dandan Sun, Guangyuan Zhang, Cheng Sun, Miao Wang, Danyang Ji, Wei Yang
Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified Bletilla striata polysaccharides (BSPs) copolymers was successfully developed. Particle size, zeta potential, encapsulation efficiency (EE), and loading capacity (LC) were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC). The hemolysis and in vitro anticancer activity were studied...
December 2, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27918129/photo-modulated-therapeutic-protein-release-from-a-hydrogel-depot-using-visible-light
#19
Johan S Basuki, Fengxiang Qie, Xavier Mulet, Randy Suryadinata, Aditya V Vashi, Yong Y Peng, Lingli Li, Xiaojuan Hao, Tianwei Tan, Timothy C Hughes
The use of biomacromolecular therapeutics has revolutionized disease treatment, but frequent injections are required owing to their short half-life in vivo. Thus there is a need for a drug delivery system that acts as a reservoir and releases the drug remotely "on demand". Here we demonstrate a simple light-triggered local drug delivery system through photo-thermal interactions of polymer-coated gold nanoparticles (AuNPs) inside an agarose hydrogel as therapeutic depot. Localized temperature increase induced by the visible light exposure caused reversible softening of the hydrogel matrix to release the pre-loaded therapeutics...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27917408/prostate-specific-membrane-antigen-targeted-polymersomes-for-delivering-mocetinostat-and-docetaxel-to-prostate-cancer-cell-spheroids
#20
Fataneh Karandish, Manas K Haldar, Seungyong You, Amanda E Brooks, Benjamin D Brooks, Bin Guo, Yongki Choi, Sanku Mallik
Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat...
November 30, 2016: ACS Omega
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