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[PMID]:29330050
[Au] Autor:Tanabe A; Nakano K; Nakakido M; Nagatoishi S; Tanaka Y; Tsumoto K; Uchimaru K; Watanabe T
[Ad] Endereço:Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
[Ti] Título:Production and characterization of a novel site-specific-modifiable anti-OX40-receptor single-chain variable fragment for targeted drug delivery.
[So] Source:Biochem Biophys Res Commun;496(2):614-620, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OX40 receptor (tumor necrosis factor receptor superfamily, member 4; CD134) is a T-cell co-stimulatory molecule that plays an important role in T-cell activation and survival. OX40 receptor is activated by its ligand, OX40L; and modulation of the OX40-OX40L interaction is a promising target for the treatment of autoimmune diseases and cancers. Here, we generated a high-affinity anti-OX40 single-chain variable fragment carrying a C-terminal cysteine residue (scFvC). Physicochemical and functional analyses revealed that the scFvC bound to OX40-expressing cells and was internalized via OX40-mediated endocytosis without inducing phosphorylation of IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), an important complex in the classical NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway. In addition, mutation of the 36th cysteine residue in variable region of light chain enabled site-specific chemical modification to carboxy terminal cysteine and improved the thermal stability of the scFvC. These results suggest that this novel high-affinity anti-OX40 scFvC may be useful as a transporter for targeted delivery of small compounds, proteins, peptides, liposomes, and nanoparticles, into OX40-expressing cells for the treatment of autoimmune diseases and cancers.
[Mh] Termos MeSH primário: Imunoconjugados/imunologia
Receptores OX40/imunologia
Anticorpos de Cadeia Única/imunologia
[Mh] Termos MeSH secundário: Linhagem Celular
Sistemas de Liberação de Medicamentos
Escherichia coli/genética
Expressão Gênica
Seres Humanos
Imunoconjugados/química
Imunoconjugados/genética
Células Jurkat
Modelos Moleculares
Mutação Puntual
Estabilidade Proteica
Anticorpos de Cadeia Única/química
Anticorpos de Cadeia Única/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Immunoconjugates); 0 (Receptors, OX40); 0 (Single-Chain Antibodies)
[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:180114
[St] Status:MEDLINE


  2 / 48502 MEDLINE  
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[PMID]:29238190
[Au] Autor:Salade L; Wauthoz N; Deleu M; Vermeersch M; De Vriese C; Amighi K; Goole J
[Ad] Endereço:Laboratoire de Pharmacie Galénique et de Biopharmacie, Université libre de Bruxelles (ULB), Brussels.
[Ti] Título:Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia.
[So] Source:Int J Nanomedicine;12:8531-8543, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:The aim of the present study was to develop a ghrelin-containing formulation based on liposomes coated with chitosan intended for nose-brain delivery for the treatment of cachexia. Among the three types of liposomes developed, anionic liposomes provided the best results in terms of encapsulation efficiency (56%) and enzymatic protection against trypsin (20.6% vs 0% for ghrelin alone) and carboxylesterase (81.6% vs 17.2% for ghrelin alone). Ghrelin presented both electrostatic and hydrophobic interactions with the anionic lipid bilayer, as demonstrated by isothermal titration calorimetry. Then, anionic liposomes were coated with -(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride. The coating involved a size increment from 146.9±2.7 to 194±6.1 nm, for uncoated and coated liposomes, respectively. The ζ-potential was similarly increased from -0.3±1.2 mV to 6±0.4 mV before and after coating, respectively. Chitosan provided mucoadhesion, with an increase in mucin adsorption of 22.9%. Enhancement of permeation through the Calu3 epithelial monolayer was also observed with 10.8% of ghrelin recovered in the basal compartment in comparison to 0% for ghrelin alone. Finally, aerosols generated from two nasal devices (VP3 and SP270) intended for aqueous dispersion were characterized with either coated or uncoated liposomes. Contrarily to the SP270 device, VP3 device showed minor changes between coated and uncoated liposome aerosols, as shown by their median volume diameters of 38.4±5.76 and 37.6±5.74 µm, respectively. Overall, the results obtained in this study show that the developed formulation delivered by the VP3 device can be considered as a potential candidate for nose-brain delivery of ghrelin.
[Mh] Termos MeSH primário: Caquexia/tratamento farmacológico
Sistemas de Liberação de Medicamentos/métodos
Grelina/administração & dosagem
Lipossomos/administração & dosagem
Lipossomos/química
[Mh] Termos MeSH secundário: Administração Intranasal/instrumentação
Adsorção
Aerossóis/química
Encéfalo/efeitos dos fármacos
Quitosana/análogos & derivados
Quitosana/química
Estabilidade de Medicamentos
Grelina/química
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Mucinas/metabolismo
Compostos de Amônio Quaternário/química
Eletricidade Estática
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aerosols); 0 (Ghrelin); 0 (Liposomes); 0 (Mucins); 0 (N-(2-hydroxypropyl)-3-trimethylammonium chitosan); 0 (Quaternary Ammonium Compounds); 9012-76-4 (Chitosan)
[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:171215
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147650


  3 / 48502 MEDLINE  
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[PMID]:29238188
[Au] Autor:Zhang J; Tang H; Liu Z; Chen B
[Ad] Endereço:Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing.
[Ti] Título:Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy.
[So] Source:Int J Nanomedicine;12:8483-8493, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Portadores de Fármacos/química
Sistemas de Liberação de Medicamentos/métodos
Nanopartículas/efeitos adversos
Nanopartículas/química
[Mh] Termos MeSH secundário: Dendrímeros/administração & dosagem
Dendrímeros/química
Portadores de Fármacos/farmacologia
Seres Humanos
Lipossomos/administração & dosagem
Lipossomos/química
Micelas
Nanopartículas/administração & dosagem
Nanotecnologia/métodos
Nanotubos de Carbono/química
Neoplasias/tratamento farmacológico
Tamanho da Partícula
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Dendrimers); 0 (Drug Carriers); 0 (Liposomes); 0 (Micelles); 0 (Nanotubes, Carbon)
[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:171215
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S148359


  4 / 48502 MEDLINE  
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[PMID]:29200852
[Au] Autor:Hu Y; Ke L; Chen H; Zhuo M; Yang X; Zhao D; Zeng S; Xiao X
[Ad] Endereço:Department of Pharmaceutics, School of Pharmaceutical Science, South-Central University for Nationalities.
[Ti] Título:Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery.
[So] Source:Int J Nanomedicine;12:8411-8426, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:To avoid the side effects caused by nonspecific targeting, premature release, weak selectivity, and poor therapeutic efficacy of current nanoparticle-based systems used for drug delivery, we fabricated natural material-decorated nanoparticles as a multifunctional, membrane-controlled targeted drug delivery system. The nanocomposite material coated with a membrane was biocompatible and integrated both specific tumor targeting and responsiveness to stimulation, which improved transmission efficacy and controlled drug release. Mesoporous silica nanoparticles (MSNs), which are known for their biocompatibility and high drug-loading capacity, were selected as a model drug container and carrier. The membrane was established by the polyelectrolyte composite method from chitosan (CS) which was sensitive to the acidic tumor microenvironment, folic acid-modified CS which recognizes the folate receptor expressed on the tumor cell surface, and a CD receptor-targeted polysaccharide hyaluronic acid. We characterized the structure of the nanocomposite as well as the drug release behavior under the control of the pH-sensitive membrane switch and evaluated the antitumor efficacy of the system in vitro. Our results provide a basis for the design and fabrication of novel membrane-controlled nanoparticles with improved tumor-targeting therapy.
[Mh] Termos MeSH primário: Materiais Biocompatíveis/química
Sistemas de Liberação de Medicamentos
Membranas Artificiais
Nanopartículas/química
Dióxido de Silício/química
[Mh] Termos MeSH secundário: Morte Celular
Quitosana/química
Liberação Controlada de Fármacos
Endocitose
Ácido Fólico/química
Células Hep G2
Seres Humanos
Nanopartículas/ultraestrutura
Tamanho da Partícula
Porosidade
Espectroscopia de Infravermelho com Transformada de Fourier
Eletricidade Estática
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biocompatible Materials); 0 (Membranes, Artificial); 7631-86-9 (Silicon Dioxide); 9012-76-4 (Chitosan); 935E97BOY8 (Folic Acid)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S148438


  5 / 48502 MEDLINE  
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[PMID]:29200851
[Au] Autor:Mondal S; Manivasagan P; Bharathiraja S; Santha Moorthy M; Kim HH; Seo H; Lee KD; Oh J
[Ad] Endereço:Marine-Integrated Bionics Research Center.
[Ti] Título:Magnetic hydroxyapatite: a promising multifunctional platform for nanomedicine application.
[So] Source:Int J Nanomedicine;12:8389-8410, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:In this review, specific attention is paid to the development of nanostructured magnetic hydroxyapatite (MHAp) and its potential application in controlled drug/gene delivery, tissue engineering, magnetic hyperthermia treatment, and the development of contrast agents for magnetic resonance imaging. Both magnetite and hydroxyapatite materials have excellent prospects in nanomedicine with multifunctional therapeutic approaches. To date, many research articles have focused on biomedical applications of nanomaterials because of which it is very difficult to focus on any particular type of nanomaterial. This study is possibly the first effort to emphasize on the comprehensive assessment of MHAp nanostructures for biomedical applications supported with very recent experimental studies. From basic concepts to the real-life applications, the relevant characteristics of magnetic biomaterials are patented which are briefly discussed. The potential therapeutic and diagnostic ability of MHAp-nanostructured materials make them an ideal platform for future nanomedicine. We hope that this advanced review will provide a better understanding of MHAp and its important features to utilize it as a promising material for multifunctional biomedical applications.
[Mh] Termos MeSH primário: Durapatita/química
Magnetismo
Nanomedicina/métodos
[Mh] Termos MeSH secundário: Animais
Sistemas de Liberação de Medicamentos
Seres Humanos
Hipertermia Induzida
Nanopartículas de Magnetita/química
Tecidos Suporte/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Magnetite Nanoparticles); 91D9GV0Z28 (Durapatite)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147355


  6 / 48502 MEDLINE  
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[PMID]:29200850
[Au] Autor:Aliu H; Rask C; Brimnes J; Andresen TL
[Ad] Endereço:Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm.
[Ti] Título:Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen.
[So] Source:Int J Nanomedicine;12:8377-8388, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.
[Mh] Termos MeSH primário: Alérgenos/administração & dosagem
Sistemas de Liberação de Medicamentos
Imunoterapia Sublingual
[Mh] Termos MeSH secundário: Alérgenos/imunologia
Animais
Citocinas/metabolismo
Ensaio de Imunoadsorção Enzimática
Feminino
Lipídeos/química
Lipossomos
Camundongos Endogâmicos BALB C
Ovalbumina/imunologia
Pneumonia/imunologia
Pneumonia/patologia
Pneumonia/prevenção & controle
Baço/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Cytokines); 0 (Lipids); 0 (Liposomes); 9006-59-1 (Ovalbumin)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S137033


  7 / 48502 MEDLINE  
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[PMID]:28461100
[Au] Autor:Jaleel JA; Sruthi S; Pramod K
[Ad] Endereço:College of Pharmaceutical Sciences, Govt. Medical College, Kozhikode 673008, Kerala, India.
[Ti] Título:Reinforcing nanomedicine using graphene family nanomaterials.
[So] Source:J Control Release;255:218-230, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Graphene is an allotrope of carbon which consists of single layered sp hybridized carbon arranged in honey comb lattice. The fascinating properties such as ultrahigh surface area, high electrical and thermal conductivity and optical property made graphene a major point of research interest. Apart from their application in the field such as nanoelectronics, energy storage, engineering of nanocomposite materials, transistors, sensors, diodes, catalysis; they are also investigated in the field of nanomedicine. This review mainly focus on the applications of graphene in nanomedicine including drug delivery, cancer therapy, cellular imaging, gene therapy, photodynamic and photothermal therapy, antimicrobial activity, biosensing and tissue engineering, along with a short description of their unique physicochemical, biological properties and safety profile.
[Mh] Termos MeSH primário: Grafite
Nanoestruturas
[Mh] Termos MeSH secundário: Animais
Sistemas de Liberação de Medicamentos
Grafite/administração & dosagem
Grafite/química
Seres Humanos
Nanomedicina
Nanoestruturas/administração & dosagem
Nanoestruturas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
7782-42-5 (Graphite)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  8 / 48502 MEDLINE  
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[PMID]:28459243
[Au] Autor:Shashirekha G; Jena A; Mohapatra S
[Ad] Endereço:Professor, Department of Conservative Dentistry & Endodontics, Institute of Dental Sciences, Siksha 'O' Anusandhan University, Bhubaneswar, Odisha, India.
[Ti] Título:Nanotechnology in Dentistry: Clinical Applications, Benefits, and Hazards.
[So] Source:Compend Contin Educ Dent;38(5):e1-e4, 2017 May.
[Is] ISSN:2158-1797
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nanotechnology is emerging as an interdisciplinary field that is undergoing rapid development and has brought about enormous changes in medicine and dentistry. Nanomaterial-based design is able to mimic some of the mechanical and structural properties of native tissue and can promote biointegration. Nanotechnology has various applications in dentistry, including dentition renaturalization, therapy for dentin hypersensitivity, complete orthodontic realignment in a single visit, covalently bonding diamondized enamel, enhancing properties of root canal sealers, and continuous oral health maintenance using mechanical dentifrobots. A range of synthetic nanoparticles such as hydroxyapatite, bioglass, titanium, zirconia, and silver nanoparticles are proposed for dental restoration. This review focuses on the developments in the field of nanomaterials in dentistry in the form of tissue regeneration materials, implantable devices, nanocomposites, endodontic sealers etc. and issues of patient safety.
[Mh] Termos MeSH primário: Materiais Dentários
Odontologia/métodos
Nanotecnologia
[Mh] Termos MeSH secundário: Sistemas de Liberação de Medicamentos
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Dental Materials)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  9 / 48502 MEDLINE  
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[PMID]:28457894
[Au] Autor:Zupancic O; Bernkop-Schnürch A
[Ad] Endereço:Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 80/82, Center for Chemistry and Biomedicine, 6020 Innsbruck, Austria.
[Ti] Título:Lipophilic peptide character - What oral barriers fear the most.
[So] Source:J Control Release;255:242-257, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Peptide therapeutics is currently one of the fastest growing markets worldwide and consequently convenient ways of administration for these drugs are highly on demand. In particular, oral dosage forms would be preferred. A relative large molecular weight and high hydrophilicity, however, result in comparatively very low oral bioavailability being in most cases below 1%. Lipid based formulations (LBF), in particular self-emulsifying drug delivery systems (SEDDS) and solid lipid nanoparticles (SLN) as well as liposomes are among the most promising tools for oral peptide delivery. Key to success in orally delivering peptides via LBF seems to be a sufficiently high lipophilic character of those therapeutic agents. Hence, different non-covalent and covalent peptide lipidization methods from drug delivery point of view are presented. On the one hand, among non-covalent lipidization methods hydrophobic ion pairing seems to be a promising way to sufficiently increase peptide lipophilicity providing high drug payloads in the lipid phase, a protective effect against presystemic metabolism via thiol-disulphide exchange reactions and proteolysis as well as an improved intestinal membrane permeability. On the other hand, covalent methods like conjugating fatty acids via amidation, esterification, reversible aqueous lipidization (REAL) and cyclization also show potential. The present review therefore describes those lipidization methods in detail and critically evaluates their contribution in successfully overcoming the oral barriers.
[Mh] Termos MeSH primário: Lipídeos/química
Peptídeos/química
[Mh] Termos MeSH secundário: Administração Oral
Animais
Sistemas de Liberação de Medicamentos
Seres Humanos
Absorção Intestinal
Peptídeos/administração & dosagem
Peptídeos/farmacocinética
Peptídeos/uso terapêutico
Proteólise
Vacinas
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Lipids); 0 (Peptides); 0 (Vaccines)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  10 / 48502 MEDLINE  
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[PMID]:29386460
[Au] Autor:Shuto S
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Hokkaido University.
[Ti] Título:Foreword.
[So] Source:Chem Pharm Bull (Tokyo);66(2):116, 2018.
[Is] ISSN:1347-5223
[Cp] País de publicação:Japan
[La] Idioma:eng
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Antivirais/farmacologia
Nucleosídeos/farmacologia
Nucleotídeos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Antivirais/síntese química
Antivirais/química
Pesquisa Biomédica
Química Farmacêutica
Sistemas de Liberação de Medicamentos
Seres Humanos
Nucleosídeos/síntese química
Nucleosídeos/química
Nucleotídeos/síntese química
Nucleotídeos/química
[Pt] Tipo de publicação:INTRODUCTORY JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Antiviral Agents); 0 (Nucleosides); 0 (Nucleotides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180202
[St] Status:MEDLINE
[do] DOI:10.1248/cpb.c18-ctf6602



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