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1.
Int J Biol Macromol ; 254(Pt 3): 127872, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37939759

RESUMO

The pathogenesis of acute lung injury (ALI) involves various mechanisms, such as oxidative stress, inflammation, and epithelial cell apoptosis. However, current drug therapies face limitations due to issues like systemic distribution, drug degradation in vivo, and hydrophobicity. To address these challenges, we developed a pH-responsive nano-drug delivery system for delivering antioxidant peptides to treat ALI. In this study, we utilized low molecular weight chitosan (LMWC) and hyaluronic acid (HA) as carrier materials. LMWC carries a positive charge, while HA carries a negative charge. By stirring the two together, the electrostatic adsorption between LMWC and HA yielded aggregated drug carriers. To specifically target the antioxidant drug WNWAD to lung lesions and enhance therapeutic outcomes for ALI, we created a targeted drug delivery system known as HA/LMWC@WNWAD (NPs) through a 12-h stirring process. In our research, we characterized the particle size and drug release of NPs. Additionally, we assessed the targeting ability of NPs. Lastly, we evaluated the improvement of lung injury at the cellular and animal levels to investigate the therapeutic mechanism of this drug targeting delivery system.


Assuntos
Lesão Pulmonar Aguda , Nanopartículas , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Peptídeos , Lesão Pulmonar Aguda/tratamento farmacológico , Ácido Hialurônico/química , Liberação Controlada de Fármacos
3.
BMC Complement Med Ther ; 23(1): 317, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700261

RESUMO

BACKGROUND: Artemisiae Scopariae Herba (ASH) has been widely used as plant medicine in East Asia with remarkable antitumor activity. However, the underlying mechanisms have not been fully elucidated. METHODS: This study aimed to construct a multi-disciplinary approach to screen topoisomerase I (topo I) inhibitors from ASH extract, and explore the antitumor mechanisms. Bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS was used to identify chemical constitution of ASH extract as well as the topo I inhibitors, and in silico docking coupled with multiple complex networks was applied to interpret the molecular mechanisms. RESULTS: Crude ASH extract exhibited toxicogenetic and antiproliferative activities on A549 cells. A series of 34 ingredients were identified from the extract, and 6 compounds were screened as potential topo I inhibitors. Docking results showed that the formation of hydrogen bond and π-π stacking contributed most to their binding with topo I. Interrelationships among the 6 compounds, related targets and pathways were analyzed by multiple complex networks model. These networks displayed power-law degree distribution and small-world property. Statistical analysis indicated that isorhamnetin and quercetin were main active ingredients, and that chemical carcinogenesis-reactive oxygen species was the critical pathway. Electrophoretic results showed a therapeutic effect of ASH extract on the conversion of supercoiled DNA to relaxed forms, as well as potential synergistic effect of isorhamnetin and quercetin. CONCLUSIONS: The results improved current understanding of Artemisiae Scopariae Herba on the treatment of tumor. Moreover, the combination of multi-disciplinary methods provided a new strategy for the study of bioactive constituents in medicinal plants.


Assuntos
Quercetina , Ultrafiltração , Espectrometria de Massas em Tandem , Inibidores da Topoisomerase I/farmacologia , Extratos Vegetais/farmacologia
4.
J Sci Food Agric ; 103(13): 6198-6207, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37140538

RESUMO

BACKGROUND: Shortening is used widely in cookie preparation to improve quality and texture. However, large amounts of saturated and trans fatty acids present in shortening have adverse effects on human health, and much effort has been made to reduce the use of shortening. The use of oleogels might be a suitable alternative. In this study, the oleogels of high oleic sunflower oil with beeswax (BW), BW-glyceryl monopalmitate (BW-GMP), and BW-Span80 (BW-S80) were prepared and their suitability to replace shortening in cookie preparation was evaluated. RESULTS: The solid fat content of BW, BW-GMP, and BW-S80 oleogels was significantly lower than that of commercial shortening when the temperature was not higher than 35 °C. However, the oil-binding capacity of these oleogels was almost similar to that of shortening. The crystals in the shortening and oleogels were ß' form mainly; however, the morphology of crystal aggregates in these oleogels was different from that of shortening. The textural and rheological properties of doughs prepared with the oleogels were similar, and clearly different from those of dough with commercial shortening. The breaking strengths of cookies made with oleogels were lower than that of cookies prepared with shortening. However, cookies containing BW-GMP and BW-S80 oleogels were similar in density and color to those prepared with shortening. CONCLUSION: The textural properties and color of cookies with BW-GMP and BW-S80 oleogels were very similar to those of the cookies containing commercial shortening. The BW-GMP and BW-S80 oleogels could act as alternatives to shortening in the preparation of cookies. © 2023 Society of Chemical Industry.


Assuntos
Alimentos , Óleo de Girassol/química , Culinária , Reologia
5.
Fitoterapia ; 168: 105525, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37150329

RESUMO

Scutellaria baicalensis Georgi (SBG) has been widely used as medical plant in East Asia with remarkable anti-cancer activity. However, the underlying mechanisms are still confused. In this study, an integrated analysis was conducted to screen topoisomerase I (topo I) inhibitors from flavonoids of SBG and investigate the anti-cancer mechanisms, containing bioaffinity ultrafiltration UPLC-ESI-TripleTOF-MS/MS, molecular docking, and multiple complex networks. The SBG extract exhibited notable cytotoxic activity on Hela cells. Five flavonoids were identified as potential topo I inhibitors, including skullcapflavone II, wogonin, chrysin, oroxylin A, and tenaxin I. Their ESI-MS/MS spectra showed that RDA reaction and neutral molecule loss were the main fragment patterns. Docking results demonstrated that π-π interaction and the formation of hydrogen bond contributed most to their binding with topo I. The selected compounds, related target proteins and pathways were integrated into target-based multiple complex networks, which consisted of three subnetworks. Statistical and topological analysis of these networks revealed a series of characteristics, including scale-free property with power-law degree distribution, Poisson degree distribution, and small-world property. Chrysin, wogonin, and oroxylin A exhibited as main active components with much higher degree values. Chemical carcinogenesis-receptor activation (hsa05207) was considered as critical pathway due to remarkable centrality indexes. Additionally, potential synergistic effect of wogonin and chrysin was observed on the conversion of supercoiled DNA to relaxed forms. These results improved current understanding of flavonoid-rich plants on the treatment of cancer. Moreover, the multi-disciplinary approach provided a new strategy for the research of natural products from medical plants.


Assuntos
Scutellaria baicalensis , Espectrometria de Massas em Tandem , Humanos , Scutellaria baicalensis/química , Espectrometria de Massas em Tandem/métodos , Simulação de Acoplamento Molecular , Inibidores da Topoisomerase I/farmacologia , Ultrafiltração , Células HeLa , Estrutura Molecular , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flavonoides/química
6.
Drug Deliv Transl Res ; 12(1): 167-179, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33432521

RESUMO

Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor.


Assuntos
Ácido Fólico , Micelas , Linhagem Celular Tumoral , Doxorrubicina/química , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ácido Fólico/química
7.
Front Bioeng Biotechnol ; 9: 763661, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660562

RESUMO

Plant virus nanoparticles (PVNPs) have been widely used for drug delivery, antibody development and medical imaging because of their good biodegradation and biocompatibility. Particles of pepper mild mottle virus (PMMoV) are elongated and may be useful as drug carriers because their shape favours long circulation, preferential distribution and increased cellular uptake. Moreover, its effective degradation in an acidic microenvironment enables a pH-responsive release of the encapsulated drug. In this study, genetic engineering techniques were used to form rod-shaped structures of nanoparticles (PMMoV) and folated-modified PMMoV nanotubes were prepared by polyethylene glycol (PEG) to provide targeted delivery of paclitaxel (PTX). FA@PMMoV@PTX nanotubes were designed to selectively target tumor cells and to release the encapsulated PTX in response to pH. Efficient cell uptake of FA@PMMoV@PTX nanotubes was observed when incubated with tumor cells, and FA@PMMoV@PTX nanotubes had superior cytotoxicity to free PTX, as reflected by cell survival and apoptosis. This system is a strong candidate for use in developing improved strategies for targeted treatment of tumors.

8.
Biomater Sci ; 9(4): 1232-1236, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33570052

RESUMO

A mitochondria-targeted dual-functional aggregation-induced emission luminogen, TPP-TPEDCH, was rationally designed and developed for intracellular mitochondrial imaging and photodynamic therapy. TPP-TPEDCH clearly showed the movements of mitochondria at various time points. Moreover, both in vitro and in vivo results demonstrated its excellent ROS generation ability and strong antitumor activity.


Assuntos
Fotoquimioterapia , Mitocôndrias
9.
J Nanosci Nanotechnol ; 20(4): 2402-2407, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492254

RESUMO

Supercapacitors are regarded as a promising energy storage system. Transition metal compounds have been widely used as electrode materials for pseudocapacitors, which possess variable oxidation valence states. Among them, Ni-based materials have drawn a substantial amount of attention. In this work, Ni nanoparticles (NiNPs/NiF) were successfully synthesized on Ni foam by a facile ion implantation method and first studied for the supercapacitor application. At the same time, NiO nanofibers were grown on a Ni foam (NiOF/NiF) for comparison. The NiNPs/NiF electrode delivered a better performance than the NiOF/NiF. The NiNPs/NiF electrode showed a high specific capacitance of 3862 F g-1 at 5 A g-1 and good long-term endurance at a current density of 50 A g-1 after a charge-discharge test of 1000 cycles. The good performance can be attributed to the uniform deposition of the Ni nanoparticles, which provided abundant active sites for the Faradaic reaction. Moreover, the three-dimensional (3D) structure of Ni foam facilitated the electron transfer between the electrode and electrolyte. The excellent performance and facile fabrication make the NiNPs/NiF electrode a promising candidate for high-performance supercapacitors.

10.
Front Pharmacol ; 11: 593518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33746741

RESUMO

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). As poziotinib is partially metabolized by CYPs, cocktail probes are used to study the interaction between drugs metabolized by each CYP subtype. Midazolam, bupropion, dextromethorphan, tolbutamide, chlorzoxazone, phenacetin, and their metabolites were used to examine the effects of poziotinib on the activity of cyp1a2, 2b1, 2d1, 2c11, 2e1, and 3a1/2, respectively. The in vitro experiment was carried out by using rat liver microsomes (RLMs), whereas the in vivo experiment involved the comparison of the pharmacokinetic parameters of the probes after co-administration with poziotinib to rats to those of control rats treated with only probes. UPLC-MS/MS was used to detect the probes and their metabolites in rat plasma and rat liver microsomes. The in vitro results revealed that the half-maximal inhibitory concentration values of bupropion and tolbutamide in RLMs were 8.79 and 20.17 µM, respectively, indicating that poziotinib showed varying degrees of inhibition toward cyp2b1 and cyp2c11. Poziotinib was a competitive inhibitor of cyp2b1 and cyp2c11, with Ki values of 16.18 and 17.66 µM, respectively. No time- or concentration-dependence of inhibition by poziotinib was observed toward cyp2b1 and cyp2c11 in RLMs. Additionally, no obvious inhibitory effects were observed on the activity of cyp1a2, cyp2d1, cyp2e1, and cyp3a1/2. In vivo analysis revealed that bupropion, tolbutamide, phenacetin, and chlorzoxazone showed significantly different pharmacokinetic parameters after administration (p < 0.05); there was no significant difference in the pharmacokinetic parameters of dextromethorphan and midazolam. These results show that poziotinib inhibited cyp2b1 and cyp2c11, but induced cyp1a2 and cyp2e1 in rats. Thus, poziotinib inhibited cyp2b1 and cyp2c11 activity in rats, suggesting the possibility of interactions between poziotinib and these CYP substrates and the need for caution when combining them in clinical settings.

11.
Acta Biomater ; 77: 15-27, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30126591

RESUMO

Scaffold-based tissue engineering is widely used for spinal cord injury (SCI) treatment by creating supporting and guiding neuronal tissue regeneration. However, how to enhance the axonal regeneration capacity following SCI still remains a challenge. Polysialic acid (PSA), a natural, biodegradable polysaccharide, has been increasingly explored for controlling central nervous system (CNS) development by regulating cell adhesive properties and promoting axonal growth. Here, a polycaprolactone (PCL)/PSA hybrid nanofiber scaffold encapsulating glucocorticoid methylprednisolone (MP) is developed for SCI treatment. Rat models with spinal cord transection is established and the PCL/PSA/MP scaffold is transplanted into lesion area. PCL/PSA/MP scaffold decreases tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release by inhibiting ionized calcium-binding adapter molecule 1 (Iba1) positive microglia/macrophage activation and reduces apoptosis-associated Caspase-3 protein expression. In addition, the PCL/PSA/MP scaffold inhibits axonal demyelination and glial fibrillary acidic protein (GFAP) expression, increases neurofilament 200 (NF-200) expression and improves functional outcome by Basso, Beattie and Bresnahan (BBB) test. These results demonstrate the therapeutic potential of PSA hybrid nanofiber scaffold in promoting axonal growth and enhancing the functional recovery following SCI. STATEMENT OF SIGNIFICANCE: Scaffold-based tissue engineering is widely used for spinal cord injury (SCI) treatment by creating supporting and guiding neuronal tissue regeneration. And how to enhance the axonal regeneration capacity following SCI still remains a challenge. Polysialic acid (PSA), a natural, biodegradable polysaccharide, has been increasingly explored for controlling central nervous system (CNS) development by regulating cell adhesive properties and promoting axonal growth. However, in vivo therapeutic effect of PSA scaffolds towards SCI is still lack of evidence and needs to be further explored. In this study, a novel electrospun polycaprolactone/PSA scaffold loaded with methylprednisolone (MP) was developed to achieve efficient therapeutic effects towards SCI. And we believe that it broadens the application of PSA for SCI treatment.


Assuntos
Nanofibras/química , Regeneração Nervosa/efeitos dos fármacos , Poliésteres/química , Ácidos Siálicos/química , Traumatismos da Medula Espinal/terapia , Animais , Animais Recém-Nascidos , Apoptose , Astrócitos/metabolismo , Axônios/fisiologia , Caspase 3/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Glucocorticoides/administração & dosagem , Humanos , Interleucina-6/metabolismo , Metilprednisolona/administração & dosagem , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Engenharia Tecidual , Alicerces Teciduais/química , Fator de Necrose Tumoral alfa/metabolismo
12.
Carbohydr Polym ; 193: 268-280, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29773381

RESUMO

Based on the abnormally increased expression of CD44 receptors on renal tubule epithelial cells during ischemia/reperfusion-induced acute kidney injury (AKI), we developed a hyaluronic acid-curcumin (HA-CUR) polymeric prodrug targeting to epithelial cells and then relieving oxidative stress damages. The water solubility of HA-CUR was significantly enhanced and approximately 27-fold higher than that of CUR. Cellular uptake test showed HA-CUR was preferably internalized by H2O2-pretreated tubular epithelial (HK-2) cells compared with free CUR benefiting from the specific binding between HA and CD44 receptors. Biodistribution results further demonstrated the increased accumulation of HA-CUR in kidneys with 13.9-fold higher than that of free CUR. Pharmacodynamic studies indicated HA-CUR effectively ameliorated AKI, and the exact mechanism was that HA-CUR protected renal tubule epithelial cells from oxidative stress damage via inhibiting PtdIns3K-AKT-mTOR signaling pathway. Taken together, this study provides a new therapeutic strategy for the treatment of AKI based on the pathogenesis of the disease.


Assuntos
Curcumina/farmacologia , Células Epiteliais/efeitos dos fármacos , Receptores de Hialuronatos/antagonistas & inibidores , Ácido Hialurônico/farmacologia , Túbulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pró-Fármacos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Curcumina/química , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Peróxido de Hidrogênio/farmacologia , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Estrutura Molecular , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Pró-Fármacos/síntese química , Pró-Fármacos/química , Solubilidade
13.
Colloids Surf B Biointerfaces ; 161: 597-605, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29156336

RESUMO

Magnesium lithospermate B (MLB) is an active polyphenol acid with multiple pharmacological activities and poor oral bioavailability. The present research aimed to construct MLB loaded solid lipid nanoparticles (MLB-SLNs) for oral delivery to enhance its bioavailability. MLB-SLNs were prepared by solvent diffusion method and subsequently modified with polyethylene glycol monostearate (PEG-SA) superficially. The particle sizes of MLB-SLNs varied from 82.57 to 53.50nm with an improved drug loading capacity (up to 16.18%) after PEG-SA modification. Pharmacokinetic study indicated that Cmax (peak plasma MLB concentration) and AUC (area under curve) of MLB-SLNs increased significantly compared to that of MLB solution in male SD rats. The relative bioavailability of MLB-SLNs with PEG-SA modification was 753.98% compared to MLB solution administered by tail intravenous injection. The enhanced transport mechanism could be further illustrated by the results that MLB-SLNs showed higher permeability across Madin-Daby canine kidney (MDCK) epithelial cell monolayer and MLB-SLNs with smaller particle size distribution and PEG-SA modification manifested stronger cellular internalization ability on MDCK cells. Thus, PEG-SA modified solid lipid nanoparticles confirmed with enhanced cellular transport and improved oral bioavailability can be a promising oral MLB delivery system.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Lipídeos/química , Nanopartículas/química , Polietilenoglicóis/química , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Cães , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacocinética , Células Madin Darby de Rim Canino , Masculino , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley
14.
ACS Appl Mater Interfaces ; 9(41): 35548-35561, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28944659

RESUMO

Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.


Assuntos
Neoplasias Hepáticas , Meios de Contraste , Ferritinas , Genes Reporter , Humanos , Lipídeos , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita
15.
Expert Opin Investig Drugs ; 26(9): 1083-1089, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28741970

RESUMO

INTRODUCTION: Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety. Glucagon-likepeptide1 (GLP-1) receptor analogues are appealing due to the improved glycemic control in a glucose-dependent manner, modest weight loss and low risk of hypoglycemia. Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1 analogue, is currently in the phase III clinical trial for the treatment of type 2 diabetes. This article aims to review the pharmacological and clinical profiles of semaglutide based on the available clinical data. Expert opinion: Semaglutide achieved greater reduction from baseline in HbA1c in comparison to placebo. The greater proportion of patients in semaglutide group than that in placebo group achieved target HbA1c <7.0% and <6.5%, respectively. Semaglutide is the second GLP-1 analogue contributing to the reduced bodyweight and improving obesity related complications. More importantly, semaglutide is beneficial to diabetic patients with high cardiovascular risk according to the recently completed phase III trial. The incidence of gastrointestinal adverse effects increased with semaglutide dose.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/farmacologia , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Resistência à Insulina
16.
Biomaterials ; 131: 36-46, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28376364

RESUMO

The development of combinational anti-tumor therapy is of great value. Here, the thermal-sensitive and hepatic tumor cell targeting peptide-A54 modified polymer, A54-poly(ethylene glycol)-g-poly(acrylamide-co-acrylonitrile) (A54-PEG-g-p(AAm-co-AN)) can self-assemble into an 80 nm-sized micelle, which shows a thermal-sensitive behavior with an upper critical solution temperature (UCST) of 43 °C. This self-assembled and targeted A54-PEG-g-p(AAm-co-AN) micelle can co-encapsulate anti-tumor drug doxorubicin (DOX) and magnetic nanoparticles (MNPs) taking advantage of the hydrophobic core of the core-shell micellar structure, when the temperature is lower than 43 °C. A much higher accumulation of the MNPs@A54-PEG-g-p(AAm-co-AN) to the tumor navigated by the A54 targeting peptide is achieved. Due to the thermal-agent effect of the accumulated MNPs in tumor, the mild microwave (8 W) applied afterwards specifically elevates the local tumor temperature by 13 °C, compared to 6 °C without MNPs accumulation in 30 min. The greater temperature rise resulted from the thermal-agent effect of MNPs doesn't only activate the drug release inside tumor cells, but also achieve an augmented hyperthermia. A mild microwave activated, chemo-thermal combinational tumor therapy is thus developed.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Preparações de Ação Retardada/química , Doxorrubicina/uso terapêutico , Neoplasias Hepáticas/terapia , Nanopartículas de Magnetita/uso terapêutico , Micelas , Resinas Acrílicas/química , Animais , Antibióticos Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/administração & dosagem , Feminino , Humanos , Hipertermia Induzida , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/patologia , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/ultraestrutura , Camundongos Endogâmicos BALB C , Camundongos Nus , Micro-Ondas , Peptídeos/química , Polietilenoglicóis/química
17.
Sci Rep ; 6: 35910, 2016 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-27775017

RESUMO

Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 µg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Meios de Contraste/administração & dosagem , Portadores de Fármacos/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Terapia de Alvo Molecular/métodos , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Doxorrubicina/administração & dosagem , Compostos Férricos/administração & dosagem , Histocitoquímica , Humanos , Ácido Láctico/administração & dosagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Camundongos Nus , Microscopia , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Resultado do Tratamento
19.
Biosens Bioelectron ; 77: 215-9, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26409021

RESUMO

An ultra-sensitive electrochemical sensor for the detection of insulin was fabricated, using low-cost and environmentally friendly nickel nanoparticles (NiNPs) by ion implantation. The morphology and structure of the NiNPs are characterized by scanning electron microscopy (SEM), revealing diameters ranging from 4 to 8 nm. The insulin assay performances were evaluated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and chronoamperometry (I-t). The NiNPs-modified indium tin oxide electrode (NiNPs/ITO) showed excellent analytical features, including ultra-high sensitivity (2140 µAµM(-1)) for detecting low concentrations of insulin, an incredibly low detection limit (10 pM) and a wide dynamic range (100 pM to 2400 pM and 1 nM to 125 nM). In addition, the NiNPs/ITO electrode was also used to analyze the insulin concentration in bovine insulin injections. The NiNPs/ITO electrode is expected to be used as a potential biosensor for insulin.


Assuntos
Condutometria/instrumentação , Insulina/análise , Nanopartículas Metálicas/química , Microquímica/instrumentação , Microeletrodos , Níquel/química , Adsorção , Desenho de Equipamento , Análise de Falha de Equipamento , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Compostos de Estanho/química
20.
Analyst ; 140(15): 5176-83, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26034785

RESUMO

Cobalt nanoparticle modified indium tin oxide (CoNP/ITO) electrodes fabricated by ion implantation were applied for the detection of reduced glutathione (GSH). The CoNP/ITO electrode was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) detector and X-ray photoelectron spectroscopy (XPS). The assay performance with regard to GSH were evaluated by cyclic voltammetry (CV) and chronoamperometry (I-t). The proposed sensor exhibited a much higher electrocatalytic activity toward the oxidation of GSH than the bare ITO electrode, with a detection limit of 5 nM. The CoNP/ITO electrode showed enhanced electrocatalytic properties, high sensitivity, good long-term stability and reproducibility as well as a rapid response to detect GSH. In addition, the CoNP/ITO electrode was also used to analyse the GSH concentration in eye drop samples, and the results were in good agreement with the labelled values.


Assuntos
Cobalto/química , Técnicas Eletroquímicas/instrumentação , Glutationa/análise , Nanopartículas Metálicas/química , Compostos de Estanho/química , Eletrodos , Limite de Detecção , Oxirredução , Espectroscopia Fotoeletrônica , Reprodutibilidade dos Testes
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