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https://www.readbyqxmd.com/read/28646794/dexibuprofen-prevents-neurodegeneration-and-cognitive-decline-in-appswe-ps1de9-through-multiple-signaling-pathways
#1
Miren Ettcheto, Elena Sánchez-López, Laura Pons, Oriol Busquets, Jordi Olloquequi, Carlos Beas-Zarate, Merce Pallas, Maria Luisa García, Carme Auladell, Jaume Folch, Antoni Camins
The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28646655/syntheses-toxicities-and-anti-inflammation-of-h2s-donors-based-on-non-steroidal-anti-inflammatory-drugs
#2
Meng Li, Jili Li, Taofeng Zhang, Quanyi Zhao, Jie Cheng, Bin Liu, Zhen Wang, Libo Zhao, Chenwei Wang
Three series of H2S donors based on NSAIDs were synthesized and characterized by (1)H-NMR, IR and ESI-HRMS. The H2S-release abilities of all compounds were evaluated in the presence of TECP or cysteine. The results show all compounds were fast H2S-releasers, and their half-lives were in range of 0-20 min. Under the same condition, H2S released from compound 9 was more than any other compounds. In cytotoxicity aspect, all compounds but 1 and 2 displayed much lower toxicities to both LO2 and HepG2 cell lines, and the IC50 values of most compounds were over 800 μM...
June 7, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28646542/reconstitution-of-low-density-lipoproteins-with-fatty-acids-for-the-targeted-delivery-of-drugs-into-cancer-cells
#3
Chunlei Zhu, Pallab Pradhan, Da Huo, Jiajia Xue, Song Shen, Krishnendu Roy, Younan Xia
Low-density lipoproteins (LDLs) represent a novel class of nanocarriers for the targeted delivery of therapeutics into aberrant cells that overexpress the LDL receptor. Here we report a facile procedure for reconstituting the hydrophobic core of LDLs with a binary fatty acid mixture. Facilitated by the tumor targeting capability of the apolipoprotein, the reconstituted, drug-loaded LDLs can effectively target cancer cells that overexpress the LDL receptor while showing minor adverse impact on normal fibroblasts...
June 24, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#4
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28646408/a-mechanism-based-pk-pd-model-for-hematological-toxicities-induced-by-antibody-drug-conjugates
#5
Sihem Ait-Oudhia, Weiyan Zhang, Donald E Mager
Antibody-drug conjugates (ADCs) are complex drug platforms composed of monoclonal antibodies (mAbs) conjugated to potent cytotoxic drugs (payloads) via chemical linkers, enabling selective payload delivery to neoplastic cells, resulting in improved efficacy and reduced toxicity. Brentuximab vedotin (Adcetris®, SGN-35) and adotrastuzumab emtansine (Kadcyla®, T-DM1) are the two FDA-approved and commercially available ADCs, and both drugs exhibit ADC-related thrombocytopenia and neutropenia. A pharmacokinetic/pharmacodynamic (PK/PD) model for ADCs was developed to identify the analyte from each ADC that is most associated with the observed hematopoietic toxicities and to determine the role of the apparent in vivo payload release rate on the severity of thrombocytopenia and neutropenia...
June 23, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28646180/sustained-release-from-a-metal-analgesics-entrapped-within-biocidal-silver
#6
Barak Menagen, Rami Pedahzur, David Avnir
Matrices for sustained release of drugs have been based on polymers, biomaterials and oxides. The use of the major family of metals as matrices for sustained release is, to the best of our knowledge, unknown. In this context we describe a new family of bio-composites for sustained release of drugs, namely analgesic drugs entrapped within metallic silver. Synthetic methodologies were developed for the preparation of ibuprofen@Ag, naproxen@Ag, tramadol@Ag and bupivacaine@Ag composites. Detailed kinetic analysis of the release of the drugs from within the metal, is provided, demonstrating that metals can indeed serve as reservoirs for drug release...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645793/biocompatible-polymer-microneedle-for-transdermal-delivery-of-tranexamic-acid
#7
S A Machekposhti, M Soltani, P Najafizadeh, S A Ebrahimi, P Chen
Recently-introduced biocompatible polymeric microneedles offer an efficient method for drug delivery. Tranexamic acid is a novel drug for treating melasma that is administered both locally and orally and inhibits excessive melanin via melanocyte. The tranexamic acid biocompatible polymer microneedle used in this study was fabricated from PVP and methacrylic acid, using the lithography method. The required mechanical strength to pierce skin was attained by optimizing the ratio of PVP to methacrylic acid. Acute dermal toxicity was done, and drug diffusion in skin layers was simulated by calculating the diffusion coefficient of tranexamic acid in interstitial fluid (plasma)...
June 20, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28645780/salvia-miltiorrhiza-bunge-danshen-extract-attenuates-permanent-cerebral-ischemia-through-inhibiting-platelet-activation-in-rats
#8
Yu-Xiang Fei, Si-Qi Wang, Li-Jian Yang, Yan-Ying Qiu, Yi-Ze Li, Wen-Yuan Liu, Tao Xi, Wei-Rong Fang, Yun-Man Li
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28645727/inhibition-of-non-canonical-hiv-1-tat-secretion-through-the-cellular-na-k-atpase-blocks-hiv-1-infection
#9
Silvia Agostini, Hashim Ali, Chiara Vardabasso, Antonio Fittipaldi, Ennio Tasciotti, Anna Cereseto, Antonella Bugatti, Marco Rusnati, Marina Lusic, Mauro Giacca
Besides its essential role in the activation of HIV-1 gene expression, the viral Tat protein has the unusual property of trafficking in and out of cells. In contrast to Tat internalization, the mechanism involved in extracellular Tat release has so far remained elusive. Here we show that Tat secretion occurs through a Golgi-independent pathway requiring binding of Tat with three short, non-consecutive intracytoplasmic loops at the C-terminus of the cellular Na(+),K(+)-ATPase pump alpha subunit. Ouabain, a pump inhibitor, blocked this interaction and prevented Tat secretion; virions produced in the presence of this drug were less infectious, consistent the capacity of virion-associated Tat to increase HIV-1 infectivity...
June 13, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28645529/nanoparticle-based-dressing-the-future-of-wound-treatment
#10
REVIEW
Morgane Berthet, Yves Gauthier, Céline Lacroix, Bernard Verrier, Claire Monge
Reconstructing functional skin after a wound remains a challenge due to the complexity of healing. In this regard, biocompatible nanoparticles (NPs) carrying and releasing bioactive drugs in a controlled and sustained manner may significantly improve the efficacy of wound therapies compared with current treatments. Topical administration of drug-loaded NPs allows optimal delivery to the dermis and improves product efficacy. Furthermore, associating NPs with scaffolds represents a new concept of 'dressing'. Experimental in vivo, ex vivo, and in vitro models have been developed in preclinical assays to evaluate the beneficial effects of nanoparticulate dressings...
June 20, 2017: Trends in Biotechnology
https://www.readbyqxmd.com/read/28644892/r-modafinil-exerts-weak-effects-on-spatial-memory-acquisition-and-dentate-gyrus-synaptic-plasticity
#11
Bharanidharan Shanmugasundaram, Yogesh D Aher, Jana Aradska, Marija Ilic, Daniel Daba Feyissa, Predrag Kalaba, Nilima Y Aher, Vladimir Dragacevic, Babak Saber Marouf, Thierry Langer, Harald H Sitte, Harald Hoeger, Gert Lubec, Volker Korz
Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO) is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP). Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO) or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT), and its phosphorylated form (ph-DAT) in DG tissue 4 h after LTP induction were quantified by western blot analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28644728/liposomes-equipped-with-cell-penetrating-peptide-br2-enhances-chemotherapeutic-effects-of-cantharidin-against-hepatocellular-carcinoma
#12
Xue Zhang, Congcong Lin, Aiping Lu, Ge Lin, Huoji Chen, Qiang Liu, Zhijun Yang, Hongqi Zhang
A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes' effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28644630/expanding-the-therapeutic-potential-of-the-iron-chelator-deferasirox-in-the-development-of-aqueous-stable-ti-iv-anticancer-complexes
#13
Sergio A Loza-Rosas, Alexandra M Vázquez-Salgado, Kennett I Rivero, Lenny J Negrón, Yamixa Delgado, Josué A Benjamín-Rivera, Angel L Vázquez-Maldonado, Timothy B Parks, Charlene Munet-Colón, Arthur D Tinoco
The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV)...
June 23, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28644354/development-and-function-of-immune-cells-in-an-adolescent-patient-with-a-deficiency-in-the-interleukin-10-receptor
#14
Sharon Veenbergen, Marieke A van Leeuwen, Gertjan J Driessen, Rogier Kersseboom, Lilian F de Ruiter, Rolien H C Raatgeep, Dicky J Lindenbergh-Kortleve, Ytje Simons-Oosterhuis, Katharina Biermann, Dicky J J Halley, Lissy de Ridder, Johanna C Escher, Janneke N Samsom
OBJECTIVE: Monogenic defects in the interleukin-10 (IL-10) pathway are extremely rare and cause infantile-onset inflammatory bowel disease (IBD)-like pathology. Understanding how immune responses are dysregulated in monogenic IBD-like diseases can provide valuable insight in "classical" IBD pathogenesis. Here, we studied long-term immune cell development and function in an adolescent IL-10 receptor (IL10RA)-deficient patient who presented in infancy with severe colitis and fistulizing perianal disease and is currently treated with immune suppressants...
July 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28644085/pharmacokinetics-of-a-sustained-release-formulation-of-buprenorphine-after-intramuscular-and-subcutaneous-administration-to-american-kestrels-falco-sparverius
#15
David Sanchez-Migallon Guzman, Heather K Knych, Glenn H Olsen, Joanne R Paul-Murphy
Previous studies have validated the clinical use of opioids with μ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study...
June 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/28643528/modulating-release-of-ranibizumab-and-aflibercept-from-thiolated-chitosan-based-hydrogels-for-potential-treatment-of-ocular-neovascularization
#16
Miguel Moreno, Poh Yih Pow, Tan Su Teng Tabitha, Sonali Nirmal, Andreas Larsson, Krishna Radhakrishnan, Jayabalan Nirmal, Soo Tng Quah, Susana Geifman Shochat, Rupesh Agrawal, Subbu Venkatraman
BACKGROUND: This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. METHODS: Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC)...
June 23, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28643475/tailoring-of-physicochemical-properties-of-nanocarriers-for-effective-anti-cancer-applications
#17
REVIEW
Swaroop Chakraborty, Geethanjali S Dhakshinamurthy, Superb K Misra
Nanotechnology has emerged strongly as a viable option to overcome the challenge of early diagnosis and effective drug delivery, for cancer treatment. Emerging research articles have expounded the advantages of using a specific type of nanomaterial-based system called as "nanocarriers," for anti-cancer therapy. The nanocarrier system is used as a transport unit for targeted drug delivery of the therapeutic drug moiety. In order for the nanocarriers to be effective for anticancer therapy, their physicochemical parameter needs to be tuned so that bio-functionalisation can be achieved to a) allow drugs being attached to the substrate and for their controlled release, b) ensure the stability of the nanocarrier up to the point of delivery, and c) clearance of the nanocarrier after the delivery...
June 23, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28643236/multi-reservoir-phospholipid-shell-encapsulating-protamine-nanocapsules-for-co-delivery-of-letrozole-and-celecoxib-in-breast-cancer-therapy
#18
Ahmed O Elzoghby, Shaimaa K Mostafa, Maged W Helmy, Maha A ElDemellawy, Salah A Sheweita
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28643095/-local-antibiotic-therapy
#19
REVIEW
Klaus-Dieter Kühn, Nora Renz, Andrej Trampuz
The treatment of superficial wound infections with local antibiotics is considered to be problematic as it is accompanied by an increased risk of resistance development and ineffectiveness in deeper regions. On the contrary, the local application of antibiotics is useful in arthroplasty and necessary if implants are utilized. The reason for this is the prevention of a rapid biofilm formation on foreign implants and a resulting infection may remain undiscovered until it becomes chronic. Apart from exogenous material, necrotic tissue (e...
June 22, 2017: Der Unfallchirurg
https://www.readbyqxmd.com/read/28642988/development-of-pulmonary-hypertension-during-treatment-with-diazoxide-a-case-series-and-literature-review
#20
Matthew R Timlin, Alexander B Black, Heather M Delaney, Renée I Matos, Candace S Percival
Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infancy. The mainstay of medical management for CHI is diazoxide. Diazoxide inhibits insulin release from the pancreas, but also causes smooth muscle relaxation and fluid retention so it is typically given with chlorothiazide. In July 2015, the FDA issued a drug safety communication warning that pulmonary hypertension (PH) had been reported in 11 infants being treated with diazoxide and that the PH resolved with withdrawal of diazoxide...
June 22, 2017: Pediatric Cardiology
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