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Pharmaceutical Research

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https://www.readbyqxmd.com/read/29181687/mir-542-3p-appended-sorafenib-all-trans-retinoic-acid-atra-loaded-lipid-nanoparticles-to-enhance-the-anticancer-efficacy-in-gastric-cancers
#1
Tong Li, Yu Zhang, Yuan-Pu Meng, Li-Shan Bo, Wen-Bo Ke
PURPOSE: In this study, miR-542-3p appended SRF/ATRA-loaded solid lipid nanoparticle was successfully prepared and demonstrated for its therapeutic efficacy against gastric cancers. METHODS: The particles were nanosized and typically spherical in shape. In vitro release study showed that release of ATRA was significantly slower compared to that of SRF from the NPs. RESULTS: MTT assay showed that miR-542-3p have a strong inhibitory effect on the proliferation of MGC-803 cancer cells in a typical dose dependent manner...
November 27, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29168076/model-based-methods-in-the-biopharmaceutical-process-lifecycle
#2
Paul Kroll, Alexandra Hofer, Sophia Ulonska, Julian Kager, Christoph Herwig
Model-based methods are increasingly used in all areas of biopharmaceutical process technology. They can be applied in the field of experimental design, process characterization, process design, monitoring and control. Benefits of these methods are lower experimental effort, process transparency, clear rationality behind decisions and increased process robustness. The possibility of applying methods adopted from different scientific domains accelerates this trend further. In addition, model-based methods can help to implement regulatory requirements as suggested by recent Quality by Design and validation initiatives...
November 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29147818/inhalation-biopharmaceutics-progress-towards-comprehending-the-fate-of-inhaled-medicines
#3
Carsten Ehrhardt
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November 16, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29110285/chemical-and-biophysical-characteristics-of-monoclonal-antibody-solutions-containing-aggregates-formed-during-metal-catalyzed-oxidation
#4
Linda O Narhi, Quanzhou Luo, Jette Wypych, Riccardo Torosantucci, Andrea Hawe, Kiyoshi Fujimori, Yasser Nashed-Samuel, Vibha Jawa, Marisa K Joubert, Wim Jiskoot
PURPOSE: To physicochemically characterize and compare monoclonal antibody (mAb) solutions containing aggregates generated via metal catalyzed oxidation (MCO). METHODS: Two monoclonal IgG2s (mAb1 and mAb2) and one monoclonal IgG1 (rituximab) were exposed to MCO with the copper/ascorbic acid oxidative system, by using several different methods. The products obtained were characterized by complementary techniques for aggregate and particle analysis (from oligomers to micron sized species), and mass spectrometry methods to determine the residual copper content and chemical modifications of the proteins...
November 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29110284/folate-conjugated-hybrid-nanocarrier-for-targeted-letrozole-delivery-in-breast-cancer-treatment
#5
Abbas Hemati Azandaryani, Soheila Kashanian, Katayoun Derakhshandeh
PURPOSE: Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. METHODS: Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation...
November 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29110283/epha2-targeted-doxorubicin-nanoliposomes-for-osteosarcoma-treatment
#6
Fateme Haghiralsadat, Ghasem Amoabediny, Samira Naderinezhad, Kamran Nazmi, Jantine Posthuma De Boer, Behrouz Zandieh-Doulabi, Tymour Forouzanfar, Marco N Helder
PURPOSE: To employ Doxorubicin-loaded liposomes, modified with YSA-peptide to target EphA2, to reduce adverse effects against primary bone cells and maximize toxicity against Saos-2 osteosarcoma cells. METHODS: PEGylated liposomes were prepared by thin film method using Dipalmitoylphosphatidylcholine (DPPC), cholesterol and distearylphosphatidylethanolamine-polyethyleneglycol conjugate (DSPE-mPEG) in 67.9:29.1:3 M ratios, and loaded with DOX (L-DOX) by pH-gradient method...
November 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305823/semi-mechanistic-population-pharmacokinetic-modeling-of-l-histidine-disposition-and-brain-uptake-in-wildtype-and-pht1-null-mice
#7
Xiao-Xing Wang, Yang-Bing Li, Meihua R Feng, David E Smith
PURPOSE: To develop a semi-mechanistic population pharmacokinetic (PK) model to quantitate the disposition kinetics of L-histidine, a peptide-histidine transporter 1 (PHT1) substrate, in the plasma, cerebrospinal fluid and brain parenchyma of wildtype (WT) and Pht1 knockout (KO) mice. METHODS: L-[14C]Hisidine (L-His) was administrated to WT and KO mice via tail vein injection, after which plasma, cerebrospinal fluid (CSF) and brain parenchyma samples were collected...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305793/coadministration-of-polymeric-conjugates-of-docetaxel-and-cyclopamine-synergistically-inhibits-orthotopic-pancreatic-cancer-growth-and-metastasis
#8
Saud A Almawash, Goutam Mondal, Ram I Mahato
PURPOSE: The aim of this study was to determine whether co-administration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonate-graft-dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305725/gelatin-nano-coating-for-inhibiting-surface-crystallization-of-amorphous-drugs
#9
Rattavut Teerakapibal, Yue Gui, Lian Yu
PURPOSE: Inhibit the fast surface crystallization of amorphous drugs with gelatin nano-coatings. METHODS: The free surface of amorphous films of indomethacin or nifedipine was coated by a gelatin solution (type A or B) and dried. The coating's effect on surface crystallization was evaluated. Coating thickness was estimated from mass change after coating. RESULTS: For indomethacin (weak acid, pKa = 4.5), a gelatin coating of either type deposited at pH 5 and 10 inhibited its fast surface crystal growth...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305717/influence-of-low-molecular-weight-excipients-on-the-phase-behavior-of-pvpva64-amorphous-solid-dispersions
#10
Kristin Lehmkemper, Samuel O Kyeremateng, Matthias Degenhardt, Gabriele Sadowski
PURPOSE: The oral bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs) can be improved by the preparation of amorphous solid dispersions (ASDs) where the API is dissolved in polymeric excipients. Desired properties of such ASDs like storage stability, dissolution behavior, and processability can be optimized by additional excipients. In this work, the influence of so-called low-molecular-weight excipients (LMWEs) on the phase behavior of ASDs was investigated...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305671/investigation-into-the-effects-of-tenilsetam-on-markers-of-neuroinflammation-in-gfap-il6-mice
#11
Erika Gyengesi, Huazheng Liang, Christopher Millington, Sandra Sonego, Daniel Sirijovski, Dhanushka Gunawardena, Karthik Dhananjayan, Madhuri Venigalla, Garry Niedermayer, Gerald Münch
PURPOSE: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse. METHODS: From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305670/bioactive-chylomicrons-for-oral-lymphatic-targeting-of-berberine-chloride-novel-flow-blockage-assay-in-tissue-based-and-caco-2-cell-line-models
#12
Manal A Elsheikh, Yosra S R Elnaggar, Dina Y Otify, Ossama Y Abdallah
PURPOSE: To develop novel bioactive-chylomicrons to solve oral delivery obstacles of Berberine chloride and target the lymphatic system. METHODS: Berberine-loaded bioactive-chylomicrons were prepared and underwent full in vitro characterization. Intestinal permeability was appraised via both non-everted gut sac model and Caco-2 cell model. Furthermore, Bioactive-chylomicrons' cellular uptake and distribution were examined by laser scanning confocal microscopy. Finally, a novel chylomicron flow-blockage assay on tissue and cellular levels were elaborated to assess the lymphatic targeting ability...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305668/iloprost-affects-macrophage-activation-and-ccl2-concentrations-in-a-microdialysis-model-in-rats
#13
Kamel Alkhatib, Tina M Poseno, Alda Diaz Perez, Jeannine M Durdik, Julie A Stenken
PURPOSE: The hypothesis that locally-released iloprost, a synthetic prostacyclin analog, affects macrophage phenotype at a microdialysis implant in the subcutaneous space of rats was tested. Macrophage activation towards alternatively-activated phenotypes using pharmaceutical release is of interest to improve integration of implants and direct the foreign body reaction toward a successful outcome. METHODS: Macrophage cell culture was used to test iloprost macrophage activation in vitro...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305666/decorated-superparamagnetic-iron-oxide-nanoparticles-with-monoclonal-antibody-and-diethylene-triamine-pentaacetic-acid-labeled-with-thechnetium-99m-and-galium-68-for-breast-cancer-imaging
#14
Marta de Souza Albernaz, Sergio Hiroshi Toma, Jeff Clanton, Koiti Araki, Ralph Santos-Oliveira
PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305665/synergistic-effect-of-polyvinyl-alcohol-and-copovidone-in-itraconazole-amorphous-solid-dispersions
#15
Kamil Wlodarski, Feng Zhang, Tongzhou Liu, Wieslaw Sawicki, Thomas Kipping
PURPOSE: The first objective is to evaluate the feasibility of melt-extruding polyvinyl alcohol-based amorphous solid dispersions for oral drug delivery. The second objective is to investigate the miscibility between polyvinyl alcohol 4-88 and copovidone, and to characterize the properties of ternary itraconazole amorphous solid dispersions comprising both polymers. METHODS: Samples were prepared using a co-rotating, twin-screw extruder. A solution precipitation study was conducted to compare the precipitation inhibition of polyvinyl alcohol against other commonly used polymers for amorphous solid dispersions...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29305664/effect-of-formulation-and-process-parameters-on-the-disproportionation-of-indomethacin-sodium-in-buffered-lyophilized-formulations
#16
Sampada Koranne, Seema Thakral, Raj Suryanarayanan
PURPOSE: (i) To investigate buffer salt crystallization and the consequent pH shifts during the freezing stage of the lyophilization of indomethacin sodium (IMCNa) in aqueous sodium phosphate buffer. (ii) To determine the effect of pH shift on the disproportionation of IMCNa in lyophilized formulations. METHODS: Prelyophilization solutions containing IMCNa in sodium phosphate buffer, at initial buffer concentrations ranging from 10 to 100 mM (pH 7.0), and at IMCNa concentrations of 5, 10 & 15 mg/ml, were investigated...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29302821/optimization-of-weight-ratio-for-dspe-peg-tpgs-hybrid-micelles-to-improve-drug-retention-and-tumor-penetration
#17
Ya Jin, Zimei Wu, Caibin Li, Weisai Zhou, John P Shaw, Bruce C Baguley, Jianping Liu, Wenli Zhang
PURPOSE: To enhance therapeutic efficacy and prevent phlebitis caused by Asulacrine (ASL) precipitation post intravenous injection, ASL-loaded hybrid micelles with size below 40 nm were developed to improve drug retention and tumor penetration. METHODS: ASL-micelles were prepared using different weight ratios of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethyleneglycol-2000 (DSPE-PEG2000) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymers...
January 4, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29302759/regulation-of-the-human-fc-neonatal-receptor-alpha-chain-gene-fcgrt-by-microrna-3181
#18
Daniel C Ferguson, Javier G Blanco
PURPOSE: FCGRT encodes the alpha-chain component of the neonatal Fc receptor (FcRn). FcRn is critical for the trafficking of endogenous and exogenous IgG molecules and albumin in various tissues. Few regulators of FcRn expression have been identified. We investigated the epigenetic regulation of FcRn by two microRNAs (hsa-miR-3181 and hsa-miR-3136-3p) acting on FCGRT. METHODS: The binding of candidate microRNAs to the 3'-untranslated region of FCGRT was evaluated using luciferase reporter constructs in CHO cells...
January 4, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29302757/indinavir-alters-the-pharmacokinetics-of-lamivudine-partially-via-inhibition-of-multidrug-and-toxin-extrusion-protein-1-mate1
#19
Qing Li, Zhi Ye, Peng Zhu, Dong Guo, Hong Yang, Jin Huang, Wei Zhang, James E Polli, Yan Shu
PURPOSE: Lamivudine, a characterized substrate for human multidrug and toxin extrusion protein 1 (hMATE1) in vitro, was commonly used with indinavir as a therapy against human immunodeficiency virus (HIV). We aimed to investigate whether mouse MATE1 is involved in the disposition of lamivudine in vivo, and whether there is any transporter-mediated interaction between indinavir and lamivudine. METHODS: The role of MATE1 in the disposition of lamivudine was determined using Mate1 wild type (+/+) and knockout (-/-) mice...
January 4, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29299768/optimization-biopharmaceutical-profile-and-therapeutic-efficacy-of-pioglitazone-loaded-plga-peg-nanospheres-as-a-novel-strategy-for-ocular-inflammatory-disorders
#20
Marcelle Silva-Abreu, Ana Cristina Calpena, Marta Espina, Amelia M Silva, Alvaro Gimeno, María Antonia Egea, María Luisa García
PURPOSE: The main goal of this study was to encapsulate Pioglitazone (PGZ), in biodegradable polymeric nanoparticles as a new strategy for the treatment of ocular inflammatory processes. METHODS: To improve their biopharmaceutical profile for the treatment of ocular inflammatory disorders, nanospheres (NSs) of PGZ were formulated by factorial design with poly (lactic-co-glycolic acid) polyethylene glycol (PLGA-PEG). Interactions drug-polymer have been carried out by spectroscopic (X-ray spectroscopy, FTIR) and thermal methods (DSC)...
January 3, 2018: Pharmaceutical Research
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