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[PMID]:28467316
[Au] Autor:Chen R; Cai X; Ma K; Zhou Y; Wang Y; Jiang T
[Ad] Endereço:The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
[Ti] Título:The fabrication of double-layered chitosan/gelatin/genipin nanosphere coating for sequential and controlled release of therapeutic proteins.
[So] Source:Biofabrication;9(2):025028, 2017 Jun 01.
[Is] ISSN:1758-5090
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bone regeneration is a complicated process and includes a number of distinct and sequential stages of coordinated cellular actions under the regulation of multiple growth factors. Therefore, bone grafting materials in which growth factors can be incorporated and released in a programmed order in line with the bone tissue healing process may lead to desirable clinical outcomes. In the present study, a double-layered chitosan/gelatin/genipin (d-CSG/G) nanosphere coating is developed by using layer-by-layer electrophoretic deposition and genipin crosslinking. The surface morphology, physicochemical and mechanical properties of the coatings are explored. Cytochrome C is used as a therapeutic model protein and is successfully loaded on the inner and outer layers of the coating. The protein release can be controlled by the loading position, genipin concentration and thickness of the outer layer. Furthermore, the cell response to the coatings was evaluated. Real-time polymerase chain reactions, immunofluorescence staining and extracellular matrix mineralization assay confirmed that the functions of the loaded growth factor are fully preserved after fabrication. Overall, the d-CSG/G nanosphere coating could be a promising growth factor delivery system to promote bone tissue regeneration.
[Mh] Termos MeSH primário: Biomimética/métodos
Quitosana/química
Materiais Revestidos Biocompatíveis/química
Citocromos c/uso terapêutico
Gelatina/química
Iridoides/química
Nanosferas/química
[Mh] Termos MeSH secundário: Animais
Proteína Morfogenética Óssea 2/química
Calcificação Fisiológica
Bovinos
Reagentes para Ligações Cruzadas/química
Preparações de Ação Retardada
Matriz Extracelular/metabolismo
Imunofluorescência
Células Mesenquimais Estromais/citologia
Nanosferas/ultraestrutura
Osteocalcina/metabolismo
Ratos
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Recombinantes/química
Soluções
Espectroscopia de Infravermelho com Transformada de Fourier
Propriedades de Superfície
Fator de Crescimento Transformador beta/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Protein 2); 0 (Coated Materials, Biocompatible); 0 (Cross-Linking Reagents); 0 (Delayed-Action Preparations); 0 (Iridoids); 0 (Recombinant Proteins); 0 (Solutions); 0 (Transforming Growth Factor beta); 0 (recombinant human bone morphogenetic protein-2); 104982-03-8 (Osteocalcin); 9000-70-8 (Gelatin); 9007-43-6 (Cytochromes c); 9012-76-4 (Chitosan); A3V2NE52YG (genipin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1088/1758-5090/aa70c3


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[PMID]:29480848
[Au] Autor:Yammine L; Kosten TR; Cinciripini PM; Green CE; Meininger JC; Minnix JA; Newton TF
[Ad] Endereço:University of Texas Health Science Center at Houston.
[Ti] Título:Exenatide once weekly for smoking cessation: study protocol for a randomized clinical trial.
[So] Source:Medicine (Baltimore);97(2):e9567, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cigarette smoking is the greatest preventable cause of morbidity and premature mortality in the United States. Approved pharmacological treatments for smoking cessation are marginally effective, underscoring the need for improved pharmacotherapies. A novel approach might use glucagon-like peptide-1 (GLP-1) agonists, which reduce alcohol and drug use in preclinical studies. GLP-1 is produced in the intestinal L-cells and in the hindbrain. The peptide maintains glucose homeostasis and reduces food intake. Several GLP-1 agonists are used clinically to treat type 2 diabetes and obesity, but none have been tested in humans to reduce smoking. AIMS: We will examine whether extended-release exenatide reduces smoking, craving, and withdrawal symptoms, as well as cue-induced craving for cigarettes. METHODS: We will enroll prediabetic and/or overweight treatment seeking smokers (n = 90) into a double-blind, placebo-controlled, randomized clinical trial. Participants will be randomized in a 1:1 ratio to receive exenatide or placebo. All participants will receive transdermal nicotine replacement therapy (NRT) and behavioral counseling. Abstinence from smoking (verified via expired CO level of ≤5 ppm), craving (Questionnaire of Smoking Urges score), and withdrawal symptoms (Wisconsin Scale of Withdrawal Symptoms score) will be assessed weekly during 6 weeks of treatment and at 1 and 4 weeks posttreatment. Cue-induced craving for cigarettes will be assessed at baseline and at 3 weeks of treatment following virtual reality exposure. EXPECTED OUTCOMES: We hypothesize that exenatide will increase the number of participants able to achieve complete smoking abstinence above that achieved via standard NRT and that exenatide will reduce craving and withdrawal symptoms, as well as cue-induced craving for cigarettes.
[Mh] Termos MeSH primário: Peptídeo 1 Semelhante ao Glucagon/agonistas
Peptídeos/administração & dosagem
Abandono do Hábito de Fumar
Fumar/tratamento farmacológico
Peçonhas/administração & dosagem
[Mh] Termos MeSH secundário: Administração Cutânea
Adolescente
Adulto
Idoso
Aconselhamento
Fissura/efeitos dos fármacos
Preparações de Ação Retardada
Método Duplo-Cego
Esquema de Medicação
Seres Humanos
Meia-Idade
Abandono do Hábito de Fumar/métodos
Síndrome de Abstinência a Substâncias/tratamento farmacológico
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Peptides); 0 (Venoms); 89750-14-1 (Glucagon-Like Peptide 1); 9P1872D4OL (exenatide)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180227
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009567


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[PMID]:29184399
[Au] Autor:Wu C; Xu J; Hao Y; Zhao Y; Qiu Y; Jiang J; Yu T; Ji P; Liu Y
[Ad] Endereço:Pharmacy School, Jinzhou Medical University, Jinzhou, China.
[Ti] Título:Application of a lipid-coated hollow calcium phosphate nanoparticle in synergistic co-delivery of doxorubicin and paclitaxel for the treatment of human lung cancer A549 cells.
[So] Source:Int J Nanomedicine;12:7979-7992, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:In this study, we developed a lipid-coated hollow calcium phosphate (LCP) nanoparticle for the combined application of two chemotherapeutic drugs to human lung cancer A549 cells. Hydrophilic doxorubicin (DOX) was incorporated into the hollow structure of hollow calcium phosphate (HCP), and a lipid bilayer containing hydrophobic paclitaxel (PTX) was subsequently coated on the surface of HCP. The study on combinational effects demonstrated that the combination of DOX and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells. The particle size, zeta potential, and encapsulation efficiency were measured to obtain optimal values: particle size was 335.0 3.2 nm, zeta potential -41.1 mV, and encapsulation efficiency 80.40%±2.24%. An in vitro release study indicated that LCP produced a sustained drug release. A549 cells had a better uptake of LCP with good biocompatibility. Furthermore, in vitro cytotoxicity experiment, apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on LCP had significant synergistic anti-tumor activity. All conclusions suggested that LCP is a promising platform for co-delivery of multiple anti-tumor drugs.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Nanopartículas/administração & dosagem
Nanopartículas/química
Fosfolipídeos/química
[Mh] Termos MeSH secundário: Células A549
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética
Apoptose/efeitos dos fármacos
Fosfatos de Cálcio/química
Caspase 3/metabolismo
Preparações de Ação Retardada/administração & dosagem
Preparações de Ação Retardada/química
Doxorrubicina/administração & dosagem
Doxorrubicina/química
Seres Humanos
Camundongos Nus
Paclitaxel/administração & dosagem
Paclitaxel/química
Tamanho da Partícula
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Phosphates); 0 (Delayed-Action Preparations); 0 (Phospholipids); 80168379AG (Doxorubicin); 97Z1WI3NDX (calcium phosphate); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S140957


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[PMID]:29441998
[Au] Autor:Saab M; Issa M; Samy W; El-Maradny H
[Ti] Título:Alternative approaches in formulating floating hollow tablets sublimation technique; a platform tailored drug release profile.
[So] Source:Pharmazie;71(12):701-708, 2016 Dec 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to formulate floating hollow tablets of salbutamol sulphate with a platform tailored drug release profile to attain a controllable drug release. Eight formulations (F1-F8) were prepared using sublimation technique. L-menthol was directly compressed as sublimable core followed by compression coating of hydroxypropylmethyl cellulose (HPMC-K15M) or polyethylene oxide (PEO-WSR301) as release retarding polymer coat. Tablets were then subjected to heat to allow sublimation of the core. The effect of polymer type and that of different drug coat/core distribution on swelling and drug release profile was studied. FTIR and DSC revealed the absence of any drug-excipients interaction. Tablets showed a hollow morphology, resulting in low density tablets that floated for over 24 hours without lag time. Moreover, different drug coat/core distribution resulted in controllable release profiles. Based on these results, an optimum drug release behavior was recorded for HPMC-based hollow tablets consisting of 2:1 drug coat/core distribution ratio (F4), revealing a zero order drug release for over 14 hours. Furthermore, F4 showed no changes in drug content, floating properties and drug release profile upon exposure to accelerated stability conditions.
[Mh] Termos MeSH primário: Preparações de Ação Retardada/química
Comprimidos/química
[Mh] Termos MeSH secundário: Varredura Diferencial de Calorimetria
Química Farmacêutica
Composição de Medicamentos
Liberação Controlada de Fármacos
Estabilidade de Medicamentos
Excipientes
Dureza
Derivados da Hipromelose
Mentol/administração & dosagem
Mentol/química
Solubilidade
Espectroscopia de Infravermelho com Transformada de Fourier
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Excipients); 0 (Tablets); 1490-04-6 (Menthol); 3NXW29V3WO (Hypromellose Derivatives)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.5186


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[PMID]:29381026
[Au] Autor:Jiang D; Zhang X; Yu D; Xiao Y; Wang T; Su Z; Liu Y; Zhang N
[Ti] Título:Tumor-Microenvironment Relaxivity-Changeable Gd-Loaded Poly(L-lysine)/Carboxymethyl Chitosan Nanoparticles as Cancer-Recognizable Magnetic Resonance Imaging Contrast Agents.
[So] Source:J Biomed Nanotechnol;13(3):243-54, 2017 Mar.
[Is] ISSN:1550-7033
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Magnetic resonance imaging (MRI) contrast agents with tumor-microenvironment changeable relaxivity are effective to increase the sensitivity and selectivity of MRI in tumor diagnosis. In this study, pH-sensitive Gd-loaded Poly(L-lysine)/ Carboxymethyl Chitosan Nanoparticles (Gd-PCNPs) were developed as relaxivity-changeable MRI contrast agents based on the "on­off" switchable strategy. The "on­off" switchable nano-contrast agents were capable of releasing Gd3+ in response to physical stimulation, with structure transformed. Gd-PCNPs could responsively disassemble in an acidic tumor-microenvironment and increase the exchange of protons between water molecules and Gd3+ ions, thus selectively enhance the relaxivity in tumor area. Gd-PCNPs were self-assembled via electrostatic interaction between poly(L-lysine)-diethylenetriamine pentaacetic acid-gadolinium and pH-sensitive carboxymethyl chitosan (CMCS). Gd-PCNPs exhibited spherical shape with uniform particle size distribution (166.00 ± 1 .71 nm) and negative zeta potential (­13.2 ± 4.7 mV). The relaxivity of Gd-PCNPs increased from 6.618 mM­1 · s­1 to 10.008 mM­1 · s­1 when the pH values decrease from 7.4 to 6.0, which was higher than Magnevist® (3.924 mM­1 · s­1 at both pH 7.4 and 6.0 (p <0 05). The changeable relaxivity of Gd/PCNPs would result in enhanced tumor/normal tissue signal contrast, which was verified by in vivo MRI test. In vivo MRI test showed that the signal of Gd-PCNPs was significantly enhanced with prolonged imaging time in tumor tissue compared to Magnevist® (p <0 05). Furthermore, Gd-PCNPs exhibited unobvious in vitro cytotoxicity under the experimental concentrations in B16 cells. No obvious damage was observed in the different tissues of mice. These results indicated that the relaxivity-changeable Gd-PCNPs exhibited demonstrated sensitivity and selectivity in tumor diagnosis with a great potential as a novel MRI contrast agent.
[Mh] Termos MeSH primário: Quitosana/análogos & derivados
Quitosana/química
Preparações de Ação Retardada/síntese química
Gadolínio/química
Imagem por Ressonância Magnética/métodos
Nanocápsulas/química
Neoplasias Experimentais/diagnóstico por imagem
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Feminino
Camundongos
Nanocápsulas/ultraestrutura
Neoplasias Experimentais/patologia
Tamanho da Partícula
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Nanocapsules); 0 (carboxymethyl-chitosan); 9012-76-4 (Chitosan); AU0V1LM3JT (Gadolinium)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE


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[PMID]:28457963
[Au] Autor:Nagasaki Y; Mizukoshi Y; Gao Z; Feliciano CP; Chang K; Sekiyama H; Kimura H
[Ad] Endereço:Department of Material Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8
[Ti] Título:Development of a local anesthetic lidocaine-loaded redox-active injectable gel for postoperative pain management.
[So] Source:Acta Biomater;57:127-135, 2017 Jul 15.
[Is] ISSN:1878-7568
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although local anesthesia is commonly applied for pain relief, there are several issues such as its short duration of action and low effectiveness at the areas of inflammation due to the acidic pH. The presence of excessive amount of reactive oxygen species (ROS) is known to induce inflammation and aggravate pain. To resolve these issues, we developed a redox-active injectable gel (RIG) with ROS-scavenging activity. RIG was prepared by mixing polyamine-b-poly(ethylene glycol)-b-polyamine with nitroxide radical moieties as side chains on the polyamine segments (PMNT-b-PEG-b-PMNT) with a polyanion, which formed a flower-type micelle via electrostatic complexation. Lidocaine could be stably incorporated in its core. When the temperature of the solution was increased to 37°C, the PIC-type flower micelle transformed to gel. The continuous release of lidocaine from the gel was observed for more than three days, without remarkable initial burst, which is probably owing to the stable entrapment of lidocaine in the PIC core of the gel. We evaluated the analgesic effect of RIG in carrageenan-induced arthritis mouse model. Results showed that lidocaine-loaded RIG has stronger and longer analgesic effect when administered in inflamed areas. In contrast, while the use of non-complexed lidocaine did not show analgesic effect one day after its administration. Note that no effect was observed when PIC-type flower micelle without ROS-scavenging ability was used. These findings suggest that local anesthetic-loaded RIG can effectively reduce the number of injection times and limit the side effects associated with the use of anti-inflammatory drugs for postoperative pain management. STATEMENT OF SIGNIFICANCE: 1. We have been working on nanomaterials, which effectively eliminate ROS, avoiding dysfunction of mitochondria in healthy cells. 2. We designed redox injectable gel using polyion complexed flower type micelle, which can eliminates ROS locally. 3. We could prepare local anesthesia-loaded redox injectable gel (lido@RIG). 4. Drug release could be extended by local administration of lido@RIG. 5. Deprotonation of lidocaine improved anesthetic effect because ROS were eliminated locally by RIG. 6. Local inflammation could be also suppressed by lido@RIG.
[Mh] Termos MeSH primário: Anestésicos Locais
Lidocaína
Manejo da Dor/métodos
Dor Pós-Operatória/tratamento farmacológico
[Mh] Termos MeSH secundário: Anestésicos Locais/química
Anestésicos Locais/farmacocinética
Anestésicos Locais/farmacologia
Animais
Preparações de Ação Retardada/química
Preparações de Ação Retardada/farmacocinética
Preparações de Ação Retardada/farmacologia
Lidocaína/química
Lidocaína/farmacocinética
Lidocaína/farmacologia
Masculino
Camundongos
Camundongos Endogâmicos ICR
Dor Pós-Operatória/fisiopatologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anesthetics, Local); 0 (Delayed-Action Preparations); 98PI200987 (Lidocaine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:28457961
[Au] Autor:Abu-Awwad HAM; Thiagarajan L; Dixon JE
[Ad] Endereço:Wolfson Centre for Stem Cells, Tissue Engineering, and Modelling (STEM), Centre of Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK.
[Ti] Título:Controlled release of GAG-binding enhanced transduction (GET) peptides for sustained and highly efficient intracellular delivery.
[So] Source:Acta Biomater;57:225-237, 2017 Jul 15.
[Is] ISSN:1878-7568
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Controlled release systems for therapeutic molecules are vital to allow the sustained local delivery of their activities which direct cell behaviour and enable novel regenerative strategies. Direct programming of cells using exogenously delivered transcription factors can by-pass growth factor signalling but there is still a requirement to deliver such activity spatio-temporally. We previously developed a technology termed GAG-binding enhanced transduction (GET) to efficiently deliver a variety of cargoes intracellularly, using GAG-binding domains which promote cell targeting, and cell penetrating peptides (CPPs) which allow cell entry. Herein we demonstrate that GET system can be used in controlled release systems to mediate sustained intracellular transduction over one week. We assessed the stability and activity of GET peptides in poly(dl-lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) prepared using a S/O/W double emulsion method. Efficient encapsulation (∼65%) and tailored protein release profiles could be achieved, however intracellular transduction was significantly inhibited post-release. To retain GET peptide activity we optimized a strategy of co-encapsulation of l-Histidine, which may form a complex with the PLGA degradation products under acidic conditions. Simulations of the polymer microclimate showed that hydrolytic acidic PLGA degradation products directly inhibited GET peptide transduction activity, and use of l-Histidine significantly enhanced released protein delivery. The ability to control the intracellular transduction of functional proteins into cells will facilitate new localized delivery methods and allow approaches to direct cellular behaviour for many regenerative medicine applications. STATEMENT OF SIGNIFICANCE: The goal for regenerative medicine is to restore functional biological tissue by controlling and augmenting cellular behaviour. Either Transcription (TFs) or growth factors (GFs) can be presented to cells in spatio-temporal gradients for programming cell fate and gene expression. Here, we have created a sustained and controlled release system for GET (Glycosaminoglycan-enhanced transducing)-tagged proteins using S/O/W PLGA microparticle fabrication. We demonstrated that PLGA and its acidic degradants inhibit GET-mediated transduction, which can be overcome by using pH-activated l-Histidine. l-Histidine inhibits the electrostatic interaction of GET/PLGA and allows enhanced intracellular transduction. GET could provide a powerful tool to program cell behaviour either in gradients or with sustained delivery. We believe that our controlled release systems will allow application of GET for tissue regeneration directly by TF cellular programming.
[Mh] Termos MeSH primário: Ácido Láctico
Peptídeos
Ácido Poliglicólico
Transdução Genética/métodos
[Mh] Termos MeSH secundário: Animais
Preparações de Ação Retardada/síntese química
Preparações de Ação Retardada/química
Preparações de Ação Retardada/farmacologia
Ácido Láctico/química
Ácido Láctico/farmacologia
Camundongos
Células NIH 3T3
Peptídeos/síntese química
Peptídeos/química
Peptídeos/farmacologia
Ácido Poliglicólico/química
Ácido Poliglicólico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Peptides); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


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[PMID]:29360450
[Au] Autor:Song Z; Ye Y; Zhang Z; Shen J; Hu Z; Wang Z; Zheng J
[Ad] Endereço:Department of Orthopaedics, Suining Central Hospital, Sichuan, People's Republic of China.
[Ti] Título:Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU-mediated BDNF-loaded cationic nanobubble destruction.
[So] Source:Biochem Biophys Res Commun;496(3):911-920, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Various gene delivery systems have been widely studied for the acute spinal cord injury (SCI) treatment. In the present study, a novel type of brain-derived neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP-2 antibody (mAb /BDNF/CNBs) was prepared to provide low-intensity focused ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound-targeted tranfection to BDNF overexpressioin in neurons and efficiently inhibition neuronal apoptosis have been demonstrated, and the elaborately designed mAb /BDNF/CNBs can specifically target to the neurons. Furthermore, in a acute SCI rat model, LIFU-mediated mAb /BDNF/CNBs transfection significantly increased BDNF expression, attenuated histological injury, decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and increased BBB scores in SCI rats. LIFU-mediated mAb /BDNF/CNBs destruction significantly increase transfection efficiency of BDNF gene both in vitro and in vivo, and has a significant neuroprotective effect on the injured spinal cord. Therefore, the combination of LIFU irradiation and gene therapy through mAb /BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for gene therapy of SCI.
[Mh] Termos MeSH primário: Fator Neurotrófico Derivado do Encéfalo/administração & dosagem
Preparações de Ação Retardada/administração & dosagem
Terapia Genética/métodos
Nanocápsulas/efeitos da radiação
Sonicação/métodos
Traumatismos da Medula Espinal/genética
Traumatismos da Medula Espinal/terapia
[Mh] Termos MeSH secundário: Doença Aguda
Animais
Fator Neurotrófico Derivado do Encéfalo/genética
Cátions
Fluorcarbonetos/efeitos da radiação
Marcação de Genes/métodos
Ondas de Choque de Alta Energia
Masculino
Terapia de Alvo Molecular/métodos
Nanocápsulas/química
Nanosferas/química
Nanosferas/efeitos da radiação
Ratos
Ratos Sprague-Dawley
Traumatismos da Medula Espinal/patologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Brain-Derived Neurotrophic Factor); 0 (Cations); 0 (Delayed-Action Preparations); 0 (Fluorocarbons); 0 (Nanocapsules); 0 (brain-derived neurotrophic factor, human); CK0N3WH0SR (perflutren)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE


  9 / 32264 MEDLINE  
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[PMID]:29277612
[Au] Autor:Lee EB; Lim HD; You SH; Cheong DE; Kim GJ
[Ad] Endereço:Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Yong-Bong Dong, Buk-Gu, Gwangju 500-757, Republic of Korea.
[Ti] Título:Conditional constitutive expression system of a drug protein in vivo by positive feedback loop using an inducer-independent artificial transcription factor.
[So] Source:Biochem Biophys Res Commun;495(4):2390-2395, 2018 01 22.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bacterial-mediated drug delivery is a potential and promising strategy for the specific treatment of cancer with therapeutic molecules, especially with genetically encoded proteins. These proteins must be tightly regulated due to cytotoxicity and thus are usually expressed under the control of the P and TetA/TetR promoters in vivo. Since protein expression from these systems is triggered by exogenous inducer, periodic intravenous injection of inducer is necessary. However, these treatments can result in non-homogenous and/or inefficient expression of therapeutic proteins in vivo due to impeded diffusion and dilution of the inducer further from the injection site. To overcome these hurdles, we designed a conditional constitutive expression system equipped with the artificial transcription factor, AraC , which has two operator-binding domains and simultaneously binds to the I and I operators of the P promoter for gene expression in an arabinose-independent manner. Using this construct and the wild type protein AraC under the control of the P promoter, we constructed a self-positive feedback system to constitutively express the therapeutic protein when the induction of AraC was triggered once using arabinose. This expression system could be useful in various cancer treatment strategies using bacteria to deliver genetically encoded drugs in vivo.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Preparações de Ação Retardada/administração & dosagem
Escherichia coli/genética
Engenharia Genética/métodos
Regiões Promotoras Genéticas/genética
Proteínas Recombinantes/administração & dosagem
Proteínas Recombinantes/genética
[Mh] Termos MeSH secundário: Retroalimentação
Fatores de Transcrição
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Delayed-Action Preparations); 0 (Recombinant Proteins); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


  10 / 32264 MEDLINE  
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[PMID]:29220339
[Au] Autor:Chuong MC; Taglieri CA; Kerr SG
[Ad] Endereço:School of Pharmacy, MPCHS University, Boston, Massachusetts.
[Ti] Título:To Flavor or Not to Flavor Extemporaneous Omeprazole Liquid.
[So] Source:Int J Pharm Compd;21(6):500-512, 2017 Nov-Dec.
[Is] ISSN:1092-4221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Omeprazole is a proton pump inhibitor used to treat the symptoms of gastro esophageal reflux disease, ulcers, excess stomach acid, infection with Helicobacter pylori, and to control the gastric side effects of various drugs. The approved dosage forms in the U.S. are powder in compounding kits, delayed-release granules for oral suspension, oral delayed-release tablets, and oral delayed-release capsules. An extemporaneously compounded unsweetened oral liquid method, published in the International Journal of Pharmaceutical Compounding, was found to be commonly used by pharmacists. This project investigated the robustness of the compendium omeprazole high-performance liquid chromatographic assay in evaluating an oral liquid made from commercial delayed-release pellets, the potency of extemporaneously compounded solutions having a 1.125% v/v flavored versus unflavored samples stored at controlled cold temperatures at different time points, and examining the absorption spectrum of the flavoring agent. As part of the study, stability-indication testing was also conducted. The studies indicate that the chromatographic area under the plasma concentration-time curve of both study groups remained over 90% of the label claim during the follow-up period. The flavor did not significantly impact the pH of the oral liquid. This study further identified (1) an increase in resilient foam formation in the flavored liquid, potentially hindering dosing accuracy, (2) omeprazole is oxidized easily by 3% hydrogen peroxide, and (3) flavoring agent absorbs in an ultraviolet visible spectroscopy spectral range often used in assay detectors for quantification of drug molecules, and could interfere with assay protocols of the same.
[Mh] Termos MeSH primário: Aromatizantes/administração & dosagem
Omeprazol/química
Inibidores da Bomba de Prótons/química
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão
Preparações de Ação Retardada
Estabilidade de Medicamentos
Concentração de Íons de Hidrogênio
Omeprazol/administração & dosagem
Soluções
Espectrofotometria Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Delayed-Action Preparations); 0 (Flavoring Agents); 0 (Proton Pump Inhibitors); 0 (Solutions); KG60484QX9 (Omeprazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE



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