Base de dados : MEDLINE
Pesquisa : G02.211 [Categoria DeCS]
Referências encontradas : 3353 [refinar]
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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


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[PMID]:28465178
[Au] Autor:Das S; Ghosh S; De AK; Bera T
[Ad] Endereço:Laboratory of Nanomedicine, Division of Pharmaceutical Biotechnology, Department of Pharmaceutical Technology, Jadavpur University, 188 Raja S.C. Mallick Road, Kolkata, 700 032, W.B., India.
[Ti] Título:Oral delivery of ursolic acid-loaded nanostructured lipid carrier coated with chitosan oligosaccharides: Development, characterization, in vitro and in vivo assessment for the therapy of leishmaniasis.
[So] Source:Int J Biol Macromol;102:996-1008, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Visceral leishmaniasis (VL) is a life-threatening disease caused by Leishmania donovani due to uncontrolled parasitisation of liver, spleen, and bone marrow. Ursolic acid (UA), a promising anti-inflammatory, anti-bacterial and anti-diabetic drug used successfully for treatment of ailments. Development of new delivery system is extremely urgent for UA with better efficacy and fewer side effects. The aim of present research work was to formulate and evaluate the potential anti-leishmanial activity of UA loaded N-octyl-chitosan surface decorated nanostructured lipid carrier system (UA-NLC) for delivery to the macrophages for VL. UA-NLC were prepared and characterized for shape, size, fourier transforms scanning electron microscopy (FESEM), transmittance electron microscopy (TEM), entrapment efficiency and in vitro drug release. The results indicate that the formulated UA-NLC had nano size range (103.7±2.8nm to 143.0±3.8nm) with high drug loading capacity (12.05±0.54%) and entrapment efficiency (88.63±2.7%). Ex vivo drug uptake by macrophage was also evaluated. The UA-NLC was more effective against AG83 wild type (12 fold), SSG-R (4 fold), PMM-R (4 fold) and GE1 field isolated (3 fold) cellular amastigotes than its free form. In vivo study showed orally effective UA-NLC could suppress the parasite burden to 98.75%.
[Mh] Termos MeSH primário: Quitosana/química
Portadores de Fármacos/química
Leishmaniose/tratamento farmacológico
Lipídeos/química
Nanoestruturas/química
Triterpenos/química
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Administração Oral
Animais
Desenho de Drogas
Liberação Controlada de Fármacos
Feminino
Macrófagos/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Oligossacarídeos/química
Triterpenos/administração & dosagem
Triterpenos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Lipids); 0 (Oligosaccharides); 0 (Triterpenes); 9012-76-4 (Chitosan); P3M2575F3F (ursolic 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:170504
[St] Status:MEDLINE


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[PMID]:28456646
[Au] Autor:Ng WY; Migotto A; Ferreira TS; Lopes LB
[Ad] Endereço:Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
[Ti] Título:Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing.
[So] Source:Int J Biol Macromol;102:1104-1111, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Alginate beads containing the polar lipid monoolein were developed as a strategy to manage wet wounds by providing improved uptake of excess exudate while releasing adenosine locally for promotion of healing. To obtain monoolein-containing beads, the lipid was mixed with almond oil (2:1w/w), and emulsified within the alginate aqueous dispersion, followed by ionotropic gelation in CaCl solution. Compared to alginate-only, monoolein-alginate systems were 1.44-fold larger, their swelling ability was 1.40-fold higher and adenosine cumulative release was approximately 1.30-fold lower (at 24h). Monoolein-alginate beads were considered safe for topical application as demonstrated by the absence of changes on the viability of reconstructed skin equivalents compared to PBS. Smaller amounts of adenosine were delivered by the beads into and across damaged porcine skin (created by an incisional wound) compared to the drug aqueous solution, and cutaneous localization was favored. More specifically, the beads increased the viable skin layer/receptor phase delivery ratio by approximately 4-fold at 12h post-application. Considering the wide range of adenosine physiological effects and the importance of skin localization for its use in wound healing, these results demonstrate the potential of monoolein-containing beads for localized drug delivery and management of wet wounds.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Alginatos/química
Portadores de Fármacos/química
Glicerídeos/química
Microesferas
Pele/metabolismo
Cicatrização/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adenosina/química
Adenosina/farmacologia
Animais
Liberação Controlada de Fármacos
Ácido Glucurônico/química
Ácidos Hexurônicos/química
Permeabilidade
Suínos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alginates); 0 (Drug Carriers); 0 (Glycerides); 0 (Hexuronic Acids); 8A5D83Q4RW (Glucuronic Acid); 8C3Z4148WZ (alginic acid); C4YAD5F5G6 (monoolein); K72T3FS567 (Adenosine)
[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:170501
[St] Status:MEDLINE


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[PMID]:28450244
[Au] Autor:El-Naggar AWM; Senna MM; Mostafa TA; Helal RH
[Ad] Endereço:Radiation Chemistry Department, National Center for Radiation Research and Technology, Nasr City, Atomic Energy Authority, Cairo, Egypt. Electronic address: ab_nagga@yahoo.com.
[Ti] Título:Radiation synthesis and drug delivery properties of interpenetrating networks (IPNs) based on poly(vinyl alcohol)/ methylcellulose blend hydrogels.
[So] Source:Int J Biol Macromol;102:1045-1051, 2017 Sep.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Gamma radiation was used to prepare blend hydrogels from poly(vinyl alcohol) (PVA) and low ratios of methylcellulose (MC). The structure-property behavior was characterized by IR spectroscopy, gel fraction, differential scanning calorimetry (DSC) and swelling at room temperature and different pH values. The PVA/MC hydrogels were used as a carrier for doxycycline hyclate (DOX-h) drug. The results showed that the gel fraction of PVA/MC hydrogels decreased greatly with increasing the ratio of MC in the initial feeding solution. The PVA/MC hydrogels displayed pH-sensitive swelling character. The drug uptake-release study indicated that PVA/MC hydrogels possessed controlled release behavior and that the release process depends on pH. In this respect, the release of DOX-h drug was significant in alkaline medium.
[Mh] Termos MeSH primário: Portadores de Fármacos/química
Portadores de Fármacos/síntese química
Hidrogéis/química
Hidrogéis/síntese química
Metilcelulose/química
Álcool de Polivinil/química
[Mh] Termos MeSH secundário: Técnicas de Química Sintética
Doxiciclina/química
Liberação Controlada de Fármacos
Raios gama
Concentração de Íons de Hidrogênio
Radioquímica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Hydrogels); 9002-89-5 (Polyvinyl Alcohol); 9004-67-5 (Methylcellulose); N12000U13O (Doxycycline)
[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:170429
[St] Status:MEDLINE


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[PMID]:28456679
[Au] Autor:Khaliq NU; Oh KS; Sandra FC; Joo Y; Lee J; Byun Y; Kim IS; Kwon IC; Seo JH; Kim SY; Yuk SH
[Ad] Endereço:College of Pharmacy, Korea University, 2511 Sejongro, Sejong 30019, Republic of Korea.
[Ti] Título:Assembly of polymer micelles through the sol-gel transition for effective cancer therapy.
[So] Source:J Control Release;255:258-269, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Photo-induced apoptosis-targeted chemotherapy (PIATC) was designed and characterized to propose a new protocol for improved chemotherapy. Intratumoral injection was selected as the mode of administration of the anticancer drug, doxorubicin (DOX). To extend the retention time of DOX at the tumor parenchyma, in-situ gel formation was induced through the sol-gel transition of the Pluronic NPs containing a prodrug of DOX or a photosensitizer. The prodrug (DEVD-S-DOX) was designed to be inactive with a peptide moiety (Aspartic acid-Glutamic acid-Valine-Aspartic acid: DEVD) linked to DOX and to be cleaved into free DOX by caspase-3 expressed with apoptosis. For reactive oxygen species (ROS)-mediated apoptosis, photo-irradiation with methylene blue (MB, photosensitizer) was utilized. The sol-gel transition of the Pluronic NPs containing reactive species, DEVD-S-DOX or MB, was examined by measuring the cloud point and the gel strength in response to temperature change. ROS-mediated apoptosis was observed by measuring the ROS and membrane integrity with induced apoptosis. The in vivo antitumor efficacy of PIATC was measured with a cardiotoxicity assay in tumor-bearing mice.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Doxorrubicina/administração & dosagem
Azul de Metileno/administração & dosagem
Fotoquimioterapia
Fármacos Fotossensibilizantes/administração & dosagem
Poloxâmero/administração & dosagem
Pró-Fármacos/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacocinética
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Caspase 3/metabolismo
Linhagem Celular Tumoral
Doxorrubicina/farmacocinética
Doxorrubicina/uso terapêutico
Liberação Controlada de Fármacos
Géis
Luz
Masculino
Azul de Metileno/uso terapêutico
Camundongos Endogâmicos C3H
Micelas
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Fármacos Fotossensibilizantes/uso terapêutico
Poloxâmero/uso terapêutico
Pró-Fármacos/farmacocinética
Pró-Fármacos/uso terapêutico
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Gels); 0 (Micelles); 0 (Photosensitizing Agents); 0 (Prodrugs); 0 (Reactive Oxygen Species); 106392-12-5 (Poloxamer); 80168379AG (Doxorubicin); EC 3.4.22.- (Caspase 3); T42P99266K (Methylene Blue)
[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:170501
[St] Status:MEDLINE


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[PMID]:28450206
[Au] Autor:Deng J; Staufenbiel S; Hao S; Wang B; Dashevskiy A; Bodmeier R
[Ad] Endereço:College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.
[Ti] Título:Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules.
[So] Source:J Control Release;255:202-209, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro-in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non-sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder>wet granulation without binder>dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R =0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs.
[Mh] Termos MeSH primário: Tiorfano/análogos & derivados
[Mh] Termos MeSH secundário: Animais
Química Farmacêutica
Liberação Controlada de Fármacos
Masculino
Modelos Teóricos
Ratos Sprague-Dawley
Solubilidade
Tiorfano/sangue
Tiorfano/química
Tiorfano/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
76K53XP4TO (racecadotril); B79L7B5X3Z (Thiorphan)
[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:170429
[St] Status:MEDLINE


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[PMID]:29442030
[Au] Autor:Resende AFC; Pereira AF; Moreira TP; Patrício PSO; Fialho SL; Cunha GMF; Silva-Cunha A; Magalhães JT; Silva GR
[Ti] Título:PLGA Implants containing vancomycin and dexamethasone: development, characterization and bactericidal effects.
[So] Source:Pharmazie;71(8):439-446, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Post-operative endophthalmitis is an infection and an inflammation of the eye following a surgical procedure. Its treatment is based on drug injections into the eye. However, this treatment can lead to ocular complications. Intraocular implants could substitute the conventional therapy. Poly(lactic-co-glycolic acid) (PLGA) implants comprising on vancomycin and dexamethasone were evaluated as drug delivery system to treat endophthalmitis after cataract surgery. Implants were characterized by drug content uniformity, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Wide Angle X-ray Scattering (WAXS), Scanning Electron Microscopy (SEM) and in vitro drug release. The bactericidal effect of vancomycin, eluted from the implants, was demonstrated against Staphylococcus aureus and Staphylococcus epidermidis. The drugs were uniformly distributed in the polymer. The analytical techniques revealed the chemical integrity of the drugs incorporated into the polymer and the modification of dexamethasone semi-crystalline nature. Drugs were controlled released from implants; and the eluted vancomycin showed bactericidal effects. In conclusion, PLGA implants containing vancomycin and dexamethasone may represent a therapeutic alternative to treat post-operative endophthalmitis.
[Mh] Termos MeSH primário: Antibacterianos/administração & dosagem
Antibacterianos/uso terapêutico
Anti-Inflamatórios/administração & dosagem
Anti-Inflamatórios/uso terapêutico
Bactérias/efeitos dos fármacos
Dexametasona/administração & dosagem
Dexametasona/uso terapêutico
Portadores de Fármacos
Ácido Láctico
Ácido Poliglicólico
Infecção da Ferida Cirúrgica/prevenção & controle
Vancomicina/administração & dosagem
Vancomicina/uso terapêutico
[Mh] Termos MeSH secundário: Antibacterianos/farmacologia
Implantes de Medicamento
Liberação Controlada de Fármacos
Endoftalmite/microbiologia
Endoftalmite/prevenção & controle
Seres Humanos
Testes de Sensibilidade Microbiana
Procedimentos Cirúrgicos Oftalmológicos
Staphylococcus aureus/efeitos dos fármacos
Staphylococcus epidermidis/efeitos dos fármacos
Vancomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Anti-Inflammatory Agents); 0 (Drug Carriers); 0 (Drug Implants); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); 6Q205EH1VU (Vancomycin); 7S5I7G3JQL (Dexamethasone)
[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:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6009


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[PMID]:29200853
[Au] Autor:Briot T; Roger E; Lautram N; Verger A; Clavreul A; Lagarce F
[Ad] Endereço:Micro & Nanomédecines Translationelles - MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, MINT IBS-CHU.
[Ti] Título:Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia.
[So] Source:Int J Nanomedicine;12:8427-8442, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs), originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol HP (THP-LNCs) and LNCs associated with a mixture of Transcutol HP and Tween 80 (THP-T80-LNCs). The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant) and HL-60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine.
[Mh] Termos MeSH primário: Azacitidina/análogos & derivados
Portadores de Fármacos/química
Leucemia Mieloide Aguda/tratamento farmacológico
Nanocápsulas/administração & dosagem
[Mh] Termos MeSH secundário: Administração Oral
Antimetabólitos Antineoplásicos/administração & dosagem
Antimetabólitos Antineoplásicos/farmacocinética
Azacitidina/administração & dosagem
Azacitidina/farmacocinética
Disponibilidade Biológica
Células CACO-2
Linhagem Celular Tumoral
Portadores de Fármacos/administração & dosagem
Liberação Controlada de Fármacos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Estabilidade de Medicamentos
Etilenoglicóis/química
Seres Humanos
Lipídeos/química
Nanocápsulas/química
Polissorbatos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimetabolites, Antineoplastic); 0 (Drug Carriers); 0 (Ethylene Glycols); 0 (Lipids); 0 (Nanocapsules); 0 (Polysorbates); 776B62CQ27 (decitabine); A1A1I8X02B (carbitol); M801H13NRU (Azacitidine)
[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:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S147659


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[PMID]:29184402
[Au] Autor:Wu X; Wang L; Qiu Y; Zhang B; Hu Z; Jin R
[Ad] Endereço:Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
[Ti] Título:Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia.
[So] Source:Int J Nanomedicine;12:8025-8034, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Quinases Associadas a Receptores de Interleucina-1/antagonistas & inibidores
Nanopartículas/química
Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Compostos de Bifenilo/administração & dosagem
Compostos de Bifenilo/farmacologia
Liberação Controlada de Fármacos
Sinergismo Farmacológico
Feminino
Seres Humanos
Células Jurkat
Ácido Láctico/química
Camundongos
Nanopartículas/administração & dosagem
Nitrofenóis/administração & dosagem
Nitrofenóis/farmacologia
Piperazinas/administração & dosagem
Piperazinas/farmacologia
Ácido Poliglicólico/química
Sulfonamidas/administração & dosagem
Sulfonamidas/farmacologia
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABT-737); 0 (Biphenyl Compounds); 0 (Nitrophenols); 0 (Piperazines); 0 (Sulfonamides); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid); EC 2.7.11.1 (IRAK1 protein, human); EC 2.7.11.1 (IRAK4 protein, human); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
[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.S146875


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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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