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1.
J Chromatogr A ; 1609: 460517, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31521380

RESUMO

Poly(N-acryloyl-glucosamine-co-methylenebisacrylamide) (poly(AGA-co-MBA))-modified Fe3O4 nanoparticles were prepared via simple aqueous surface polymerization. The resultant Fe3O4@poly(AGA-co-MBA) nanoparticles were used as hydrophilic magnetic solid phase extraction sorbents. Ten aminoglycosides were selected as model analytes to evaluate the extraction performance and mechanism of the sorbents. The prepared magnetic nanoparticles were characterized by Fourier transformed infrared spectroscopy, elemental analysis, a vibrating sample magnetometer, and so on. The sorbents exhibited efficient extraction towards model analytes in hydrophilic interaction chromatography. Only 10.0 mg of sorbent was needed to adsorb analytes from 10.0 mL of a sample solution within a short time (5.0 min). Under optimized conditions, Fe3O4@poly(AGA-co-MBA) nanoparticles were applied in the sample preparation for the analysis of 10 aminoglycosides in meat samples by high-performance liquid chromatography-tandem mass spectrometry. The limits of detection (LODs) for the 10 aminoglycosides were in the range of 0.6-23.6 µg kg-1. Satisfactory recoveries of spiked meat samples from 84.6-98.3% with acceptable relative standard deviations from 3.1% to 7.8% were achieved. Compared to other reported methods for the analysis of aminoglycosides, the present work had comparable or higher sensitivities with a simple extraction procedure. The proposed hydrophilic interaction extraction sorbents are promising as powerful alternatives for extracting and enriching aminoglycosides in animal-derived food samples.


Assuntos
Acrilamidas/química , Aminoglicosídeos/isolamento & purificação , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas de Magnetita/química , Carne/análise , Extração em Fase Sólida , Adsorção , Animais , Galinhas , Cromatografia Líquida de Alta Pressão , Concentração de Íons de Hidrogênio , Limite de Detecção , Reprodutibilidade dos Testes , Temperatura Ambiente , Água/química
2.
Carbohydr Polym ; 228: 115396, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635743

RESUMO

Cellulose biopolymer was functionalized by free graft copolymerization and used as a new adsorbent to eliminate toxic inorganic pollutants from wastewater. Functional graft copolymers from cellulose were characterized by FT-IR spectroscopy, XRD, TGA, and SEM-EDX techniques.Cellulose-g-poly-(acrylamide-co-acrylic acid) polymer adsorbent showed high adsorption capacities for the Cd2+, Cu2+, Pb2+ and Zn2+ toxic metal ions, which were evidenced by the comparison with unmodified cellulose-richsamples. Cellulose-g-poly-(acrylamide-co-acrylic acid) polymer adsorbent was optimized with various adsorption parameters such as the effect of pH, contacttime, temperature, and metallic ions concentration. The maximum monolayer capacity qm calculated for Cd2+, Cu2+, Pb2+, Zn2+ were 101.73, 61.84, 209.64, and 55.04 mgg-1 respectively. Thus, these results proved that cellulose-g-poly-(acrylamide-co-acrylic acid) graft copolymer adsorbent from cellulose-rich biomass could potentially be used for the removal of pollutants from wastewater.


Assuntos
Acrilamidas/química , Celulose/química , Metais Pesados/química , Polímeros/química , Purificação da Água/métodos , Adsorção , Cinética , Águas Residuárias/análise , Poluentes Químicos da Água/química
3.
Eur J Med Chem ; 185: 111809, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683104

RESUMO

Four series of thiopyranopyrimidine AZD9291 derivatives containing acrylamide structure were designed, synthesized and evaluated for their antiproliferative activity against A549 and Hela cancer cells. Most of the compounds exhibited excellent antiproliferative activity against A549 cells. Moreover, the compounds with indole ring fluorine substituted exhibited better antiproliferative activity against Hela cells. The most promising compound 23g exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M double mutations. The IC50 value against EGFRL858R/T790M kinase was 16 nM. The compound 23g inhibits selectively against the mutated form of EGFR, with the selectivity more than 125-fold. Furthermore, compound 23g also inhibited A549 cells, Hela cells and H1975 cells proliferation at a low concentration, and the IC50 values were 0.057 µM, 0.104 µM and 0.916 µM, respectively. To further investigate the QSARs of thiopyranopyrimidine derivatives, the CoMFA (q [2] = 0.765, r2 = 0.965) and CoMSIA (q [2] = 0.875, r2 = 0.956) models on Hela cancer cells were established. The generated 3D-QSAR model was validated to be reliable and can be used for further design and optimization of novel and selective EGFR inhibitors.


Assuntos
Acrilamidas/farmacologia , Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Desenho de Drogas , Relação Quantitativa Estrutura-Atividade , Células A549 , Acrilamidas/síntese química , Acrilamidas/química , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Células Tumorais Cultivadas
4.
Eur J Med Chem ; 183: 111709, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31581004

RESUMO

A new series of AZD9291 (osimertinib) derivatives containing a sulfoxide side chain at the C-4 position of an aniline moiety were designed, synthesized and evaluated. Among these derivatives, the chiral sulfoxide derivative (-)-4i exhibited excellent inhibition of EGFR kinase activity and L858R/T790M double mutant cell proliferation, with IC50 values of 4.10 nM and 10 nM, respectively. A mechanism study elucidated that (-)-4i induced cell apoptosis and reduced phosphorylation of EGFR and AKT in a dose-dependent manner. Furthermore, (-)-4i exhibited very little apparent toxicity toward three non-tumorigenic cell lines and was less toxic than AZD9291. Moreover, the remarkable exposure (AUC0-inf: 1294.74 h ng/mL), oral bioavailability (73.69%), and relatively shorter half-life (t1/2 = 1.12 h) of (-)-4i displayed its favorable pharmacokinetic properties. Finally, the antitumor activity of (-)-4i in vivo resulted in a significant reduction of the tumor volume (TGI: 94.30%). Altogether, these results suggest that (-)-4i warrants further investigation in Non-Small cell lung cancer (NSCLC) therapy.


Assuntos
Acrilamidas/química , Compostos de Anilina/química , Antineoplásicos/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/química , Acrilamidas/farmacocinética , Compostos de Anilina/farmacocinética , Animais , Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/enzimologia , Masculino , Terapia de Alvo Molecular , Mutação , Inibidores de Proteínas Quinases/farmacocinética
5.
Int J Nanomedicine ; 14: 8059-8072, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632018

RESUMO

Background: Compared with random copolymers, block copolymerization is easier to prepare for nanoparticles with core-shell structure, and they will have better glucose sensitivity and higher insulin loading. Purpose: In our study, insulin-loaded poly (3-acrylamidophenylboronic acid-block-N-vinyl caprolactam) p(AAPBA-b-NVCL) nanoparticles were successfully prepared and were glucose-sensitive, which could effectively lower the blood sugar levels within 72 hrs. Methods: The polymer of p(AAPBA-b-NVCL) was produced by reversible addition-fragmentation chain transfer polymerization based on different ratios of 3-acrylamidophenylboronic acid (AAPBA) and N-vinylcaprolactam (NVCL), and its structure was discussed by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance . Next, the polymer was manufactured into the nanoparticles, and the characteristics of nanoparticles were detected by dynamic light scattering, lower critical solution temperature, and transmission electron microscopy. After that, the cell and animal toxicity of nanoparticles were also investigated. Results: The results demonstrated that p(AAPBA-b-NVCL) was successfully synthesized, and can be easily self-assembled to form nanoparticles. The new nanoparticles included monodisperse submicron particles, with the size of the nanoparticle ranged between 150 and 300nm and are glucose- and temperature-sensitive. Meanwhile, insulin can be easily loaded by p(AAPBA-b-NVCL) nanoparticles and an effective sustained release of insulin was observed when the nanoparticles were placed in physiological saline. Besides, MTT assay revealed that cell viability was more than 80%, and mice demonstrated no negative impact on blood biochemistry and heart, liver, spleen, lung, and kidney after intraperitoneal injection of 10 mg/kg/d of nanoparticles. This suggested that the nanoparticles were low-toxic to both cells and animals. Moreover, they could lower the blood sugar level within 72h. Conclusion: Our research suggested that these p(AAPBA-b-NVCL) nanoparticles might have the potential to be applied in a delivery system for insulin or other hypoglycemic proteins.


Assuntos
Acrilamidas/química , Ácidos Borônicos/química , Caprolactama/química , Sistemas de Liberação de Medicamentos , Glucose/análise , Insulina/administração & dosagem , Nanopartículas/química , Acrilamidas/síntese química , Animais , Glicemia/metabolismo , Ácidos Borônicos/síntese química , Caprolactama/análogos & derivados , Caprolactama/síntese química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Hidrodinâmica , Concentração de Íons de Hidrogênio , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Masculino , Camundongos , Células NIH 3T3 , Nanopartículas/ultraestrutura , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura Ambiente
6.
Soft Matter ; 15(40): 8059-8066, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31549699

RESUMO

Antimicrobial nanocomposites (NCs) are being used as an alternative antibacterial therapy for killing antibiotic-resistant pathogenic bacteria. The NCs are made of Ag nanoparticles (AgNPs) inside biocompatible hydrogel matrixes. The NCs were synthesized by the absorption of AgNO3 solution into a hydrogel matrix, followed by UV light irradiation, without using additional toxic reactants. The hydrogels used as matrixes are based on N-isopropylacrylamide (NIPAM) and copolymers with different functional groups: 2-acrylamide-2-methylpropanesulfonic acid (AMPS), N-hydroxyethylacrylamide (HEAA) and (3-acrylamidepropil)trimethylammonium chloride (APTMAC). Neutral, anionic and cationic groups were added to the matrixes in order to study their effects on the release of antibacterial species. The NCs were characterized by UV-visible spectroscopy and transmission electronic microscopy. The kinetics of the release of Ag+ ions from the NCs were followed by UV-visible spectroscopy at 300 nm. Biological experiments were based on the plate count method and agar diffusion testing against Pseudomonas aeruginosa. The bacterial death rate using the NCs is higher than when PNIPAM and nanoparticles in solution are used and seems to be related to the large amount of AgNPs contained inside the gels. In all cases, inhibition and diffusion halos were observed upon the exposure of bacterial cultures on agar to NC discs. The presence of both halos confirmed the bactericidal and bacteriostatic effects of the NCs. The reusability (prolonged use) of the materials was demonstrated until the Ag-NP content was exhausted. The NCs with a higher antibacterial capacity are based on a PNIPAM-co-6%APTMAC matrix. It was demonstrated that these NC materials have the capacity to maintain an aseptic/antiseptic zone for 7 to 15 days.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Hidrogéis/química , Nanopartículas Metálicas/química , Nanocompostos/química , Prata/química , Acrilamidas/química , Cinética , Testes de Sensibilidade Microbiana , Processos Fotoquímicos , Pseudomonas aeruginosa/efeitos dos fármacos
7.
Mater Sci Eng C Mater Biol Appl ; 105: 110094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546441

RESUMO

Cancer has emanated as a daunting menace to human-kind even though medicine, science, and technology has reached its zenith. Subsequent scarcity in the revelation of new drugs, the exigency of salvaging formerly discovered toxic drugs such as doxorubicin has emerged. The invention of drug carrier has made drug delivery imminent which is ascribable to its characteristic traits of specific targeting, effective response to stimuli and biocompatibility. In this paper, the nanoscale polymeric drug carrier poly(N,N-diethyl acrylamide) nanohydrogel has been synthesized by inverse emulsion polymerization. Lower critical solution temperature of the polymeric carrier has been modified using graphene quantum. The particle size of pure nanohydrogel was in the range of 47 to 59.5 nm, and graphene quantum dots incorporated nanohydrogels was in the range of 68.1 to 87.5 nm. Doxorubicin (hydroxyl derivative of anthracycline) release behavior as a function of time and temperature was analyzed, and the Lower critical solution temperature of the synthesized nanohydrogels has been found to be in the range of 28-42 °C. Doxorubicin release characteristics have improved significantly as the surrounding temperature of the release media was increased near to physiological temperature. Further, the cumulative release profile was fitted in the different kinetic model and found to follow a Fickian diffusion release mechanism. The hydrogel was assessed for its cytotoxicity in B16F10 cells by MTT assay. In-vivo studies were done to study the lung metastasis by melanoma cancer and the results showed a rational favorable prognosis which was confirmed by evaluating hematological parameters and the non-immunogenic nature of nanohydrogel by cytokine assay. Comprehensively, the results suggested that poly(N,N-diethyl acrylamide) nanohydrogels have potential application as an intelligent drug carrier for melanoma cancer.


Assuntos
Acrilamidas , Doxorrubicina , Portadores de Fármacos , Grafite , Hidrogéis , Neoplasias Pulmonares , Neoplasias Experimentais , Pontos Quânticos , Acrilamidas/química , Acrilamidas/farmacocinética , Acrilamidas/farmacologia , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Grafite/química , Grafite/farmacocinética , Grafite/farmacologia , Hidrogéis/química , Hidrogéis/farmacocinética , Hidrogéis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Metástase Neoplásica , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico
8.
Int J Parasitol Drugs Drug Resist ; 10: 109-117, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31472356

RESUMO

Entamoeba histolytica and Giardia duodenalis are widespread intestinal protozoan parasites which both spread via cysts that have to be ingested to infect a new host. Their environment, the small intestine for G. duodenalis and the colon for E. histolytica, contains only very limited amounts of oxygen, so both parasites generate energy by fermentation and substrate level phosphorylation rather than by oxidative phosphorylation. They both contain reducing agents able to reduce and activate nitroimidazole drugs such as metronidazole which is the gold standard drug to treat Entamoeba or Giardia infections. Although metronidazole works well in the majority of cases, it has a number of drawbacks. In animal models, the drug has carcinogenic activity, and concerns about a possible teratogenic activity remain. In addition, the treatment of G. duodenalis infections is hampered by emerging metronidazole resistance. Plant-derived drugs play a dominant role in human medicine, therefore we tested the activity of 14 isolated plant compounds belonging to seven different classes in vitro against both parasites. The tests were performed in a new setting in microtiter plates under anaerobic conditions. The compound with the highest activity was methylgerambullin, a sulphur-containing amide found in Glycosmis species of the family Rutaceae with an EC50 of 14.5 µM (6.08 µg/ml) after 24 h treatment for E. histolytica and 14.6 µM (6.14 µg/ml) for G. duodenalis. The compound was successfully synthesised in the laboratory which opens the door for the generation of new derivatives with higher activity.


Assuntos
Acrilamidas/farmacologia , Antiprotozoários/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Giardia lamblia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rutaceae/química , Acrilamidas/síntese química , Acrilamidas/química , Antiprotozoários/síntese química , Antiprotozoários/química , Entamoeba histolytica/fisiologia , Entamebíase/tratamento farmacológico , Entamebíase/parasitologia , Giardia lamblia/fisiologia , Giardíase/tratamento farmacológico , Giardíase/parasitologia , Humanos , Extratos Vegetais/química
9.
Analyst ; 144(21): 6327-6333, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31552929

RESUMO

A protein-based molecularly imprinted monolithic column was synthesized based on ionic liquids (ILs) and deep eutectic solvents (DESs) in a stainless steel column (50 mm × 4.6 mm id). An IL (1-allyl-3-butylimidazolium Br) and acrylamide were used as dual monomers. Another type of IL (1,2-bis [N,N'-vinylimidazolium] ethane bis Br) and N,N'-methylenebisacrylamide were used as dual cross-linking agents, and the DES (choline chloride : ethylene glycol 1 : 2) was used as a porogen in the preparation of a monolithic polymer. Bovine serum albumin (BSA) and lysozyme (Lyz), which differ greatly in molecular size, isoelectric point, and charge, were selected for imprinting templates to evaluate the recognition property of the green solvent-based MIP monolithic column. Some important factors, such as template-monomer molar ratio, total monomer concentration, and cross-linking density, were investigated systematically. Under optimal conditions, the MIP monolithic column obtained showed higher binding affinity for the templates than its corresponding non-imprinted (NIP) monolithic column.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Impressão Molecular , Muramidase/isolamento & purificação , Polímeros/química , Soroalbumina Bovina/isolamento & purificação , Solventes/química , Acrilamidas/química , Animais , Bovinos , Galinhas , Colina/química , Cromatografia Líquida de Alta Pressão/instrumentação , Reagentes para Ligações Cruzadas , Etilenoglicol/química , Química Verde/métodos , Líquidos Iônicos/química
10.
Int J Nanomedicine ; 14: 5397-5413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409995

RESUMO

Background: Hyperlipidemia is the elevation of low density lipoprotein levels resulting in fat deposites in arteries and their hardening and blockage.  It is the leading cause of several life threatening pathological conditions like hypertension, cardiovascular diseases, diabetes etc. Purpose: The objective of this study was to prepare and optimize nontoxic, biocompatible ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels with varying content of polymer, monomer and montmorillonite. Moreover, lipid lowering potentials were determined and compared with other approaches. Methods: ß-CD-g-MAA/Na+-MMT nanocomposite hydrogels (BM-1 to BM9) were prepared through free radical polymerization by using  ß-CD  as polymer, MAA as monomer, MBA as crosslinker and montmorillonite as clay. Developed networks were evaluated for FTIR, DSC, TGA, PXRD, SEM, sol-gel fraction (%), swelling studies, antihyperlipidemic studies and toxicity studies. Results: Optimum swelling (94.24%) and release (93.16%) were obtained at higher pH values. Based on R2 and "n" value LVT release followed zero order kinetics with Super Case II transport release mechanism, respectively. Tensile strength and elongation at break were found to be 0.0283MPa and 94.68%, respectively. Gel fraction was between 80.55 - 98.16%. Antihyperlipidemic studies revealed that LDL levels were markedly reduced from 522.24 ± 21.88mg/dl to 147.63 ± 31.5mg/dl. Toxicity studies assured the safety of developed network. Conclusion: A novel pH responsive crosslinked network containing ß-CD - g - poly (methacrylic acid) polymer and MMT was developed and optimized with excellent mechanical, swelling and release properties and lipid lowering potentials.


Assuntos
Bentonita/química , Hidrogéis/química , Lovastatina/administração & dosagem , Metacrilatos/química , Nanocompostos/química , beta-Ciclodextrinas/química , Acrilamidas/química , Administração Oral , Animais , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Cinética , Lipídeos/sangue , Nanocompostos/ultraestrutura , Especificidade de Órgãos , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Resistência à Tração , Termogravimetria , Testes de Toxicidade Aguda , Difração de Raios X
11.
PLoS One ; 14(7): e0219254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31276542

RESUMO

Thermoresponsive polymers, such as poly(N-isopropyl acrylamide) (PNIPAM), have been identified and used as cell culture substrates, taking advantage of the polymer's lower critical solution temperature (LCST) to mechanically harvest cells. This technology bypasses the use of biochemical enzymes that cleave important cell-cell and cell-matrix interactions. In this study, the process of electrospinning is used to fabricate and characterize aligned PNIPAM nanofiber scaffolds that are biocompatible and thermoresponsive. Nanofiber scaffolds produced by electrospinning possess a 3D architecture that mimics native extracellular matrix, providing physical and chemical cues to drive cell function and phenotype. We present a factorial design of experiments (DOE) approach to systematically determine the effects of different electrospinning process parameters on PNIPAM nanofiber diameter and alignment. Results show that high molecular weight PNIPAM can be successfully electrospun into both random and uniaxially aligned nanofiber mats with similar fiber diameters by simply altering the speed of the rotating mandrel collector from 10,000 to 33,000 RPM. PNIPAM nanofibers were crosslinked with OpePOSS, which was verified using FTIR. The mechanical properties of the scaffolds were characterized using dynamic mechanical analysis, revealing an order of magnitude difference in storage modulus (MPa) between cured and uncured samples. In summary, cross-linked PNIPAM nanofiber scaffolds were determined to be stable in aqueous culture, biocompatible, and thermoresponsive, enabling their use in diverse cell culture applications.


Assuntos
Resinas Acrílicas/química , Nanofibras/química , Engenharia Tecidual/métodos , Acrilamidas/química , Materiais Biocompatíveis/química , Matriz Extracelular , Polímeros/química , Tecidos Suporte/química
12.
ACS Appl Mater Interfaces ; 11(30): 26674-26683, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31282142

RESUMO

The synthesis of carbohydrate-functionalized thermosensitive poly(N-isopropylacrylamide) microgels and their ability to bind carbohydrate-binding pathogens upon temperature switch are reported. It is found that the microgels' binding affinity is increased above their lower critical solution temperature (LCST), enabling thermo-triggerable capture of pathogens. Here, a series of microgels with comparatively low mannose functionalization degrees below 1 mol % is achieved by a single polymerization step. Upon increase in mannose density, the microgel size increases, and the LCST decreases to 26 °C. Clustering with concanavalin A indicated that binding affinity is enhanced by a higher mannose content and by raising the temperature above the LCST. Binding studies with Escherichia coli confirm stronger specific interactions above the LCST and formation of mechanically stable aggregates enabling efficient separation of E. coli by filtration. For small incubation times above the LCST, the microgels' potential to release pathogens again below the LCST is confirmed also. Compared to existing switchable scaffolds, microgels nearly entirely composed of a thermosensitive material undergo a large change in volume, which allows them to drastically vary the density of ligands to switch between capture and release. This straightforward yet novel approach is likely compatible with a broad range of bioactive ligands. Therefore, thermosensitive microgels represent a promising platform for the specific capture or release of cells or pathogens.


Assuntos
Resinas Acrílicas/farmacologia , Carboidratos/química , Escherichia coli/efeitos dos fármacos , /química , Acrilamidas/química , Acrilamidas/farmacologia , Resinas Acrílicas/química , Carboidratos/farmacologia , Ligantes , Polímeros/química , Polímeros/farmacologia , Ligação Proteica/efeitos dos fármacos , Temperatura Ambiente
13.
ACS Appl Mater Interfaces ; 11(28): 25556-25568, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31265220

RESUMO

Hemocompatibility and antibacterial property are essential for blood contact devices and medical intervention materials. In this study, positively charged quaternary ammonium (QAC) and hydrophobic benzyl group (OBzl) were introduced onto hydrophilic lysine methacrylamide (LysAAm) to obtain two monomers LysAAm-QAC and LysAAm-OBzl, respectively. The structure characterizations of LysAAm-QAC and LysAAm-OBzl were determined by proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and time-of-flight secondary ion mass spectrometry. LysAAm-QAC and LysAAm-OBzl were cografted onto a silicon wafer with different feeding ratios to construct antifouling and antibacterial properties. The results of fibrinogen adsorption and platelet adhesion proved that the modified sample with the feeding ratio of 3:7 had superior antifouling property. Furthermore, an antimicrobial test with both 2 and 24 h indicated that the modified sample with the feeding ratio of 3:7 had antibacterial ability. The antifouling property was provided by the high surface coverage of LysAAm-QAC and LysAAm-OBzl (91.49%) and the hydrophilic main structure LysAAm on LysAAm-QAC and LysAAm-OBzl (water contact angle was 43.6°). The antibacterial property was improved with the proportion of LysAAm-OBzl (43.6-58.5%) because the increasing hydrophobic OBzl enhanced the ability to insert into the membrane of bacteria and raise the bactericidal efficiency. In application, LysAAm-QAC and LysAAm-OBzl with the feeding ratio of 3:7 were grafted onto the surface of poly(styrene-b-(ethylene-co-butylene)-b-styrene), and a bifunctional surface with antifouling and antibacterial properties was fabricated, which had promising applications in blood contact devices and medical intervention materials.


Assuntos
Acrilamidas/química , Antibacterianos/química , Bactérias/crescimento & desenvolvimento , Incrustação Biológica/prevenção & controle , Lisina/química , Compostos de Amônio Quaternário/química , Aderência Bacteriana , Ésteres/química , Interações Hidrofóbicas e Hidrofílicas , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Molecules ; 24(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261881

RESUMO

Herein a novel series of histone deacetylases (HDACs) and epidermal growth factor receptor (EGFR) dual inhibitors were designed and synthesized based on the structure of the approved EGFR inhibitor osimertinib (AZD9291). Among them, four compounds 5D, 5E, 9D and 9E exhibited more potent total HDAC inhibition than the approved HDAC inhibitor SAHA. However, these compounds only showed moderate to low inhibitory potency towards EGFR with compounds 5E and 9E possessing IC50 values against EGFRWT and EGFRT790M in the micromolar range. 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay revealed the potent antiproliferative activities of compounds 5D, 5E, 9D and 9E, among which 9E was even more potent against HeLa, MDA-MB-231, MDA-MB-468, HT-29 and KG-1 cell lines than SAHA and AZD9291. Further selectivity profile of 9E showed that this compound was not active against other 13 cancer-related kinases and two epigenetic targets lysine specific demethylase 1 (LSD1) and bromodomain-containing protein 4 (BRD4). These results support further structural modification of 9E to improve its EGFR inhibitory activity, which will lead to more potent and balanced HDAC and EGFR dual inhibitors as anticancer agents.


Assuntos
Acrilamidas/química , Compostos de Anilina/síntese química , Inibidores de Histona Desacetilases/síntese química , Inibidores de Proteínas Quinases/síntese química , Compostos de Anilina/química , Compostos de Anilina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Células HT29 , Células HeLa , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Humanos , Estrutura Molecular , Mutação , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
15.
Molecules ; 24(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261921

RESUMO

Piplartine (PPL), also known as piperlongumine, is a biologically active alkaloid extracted from the Piper genus which has been found to have highly effective anticancer activity against several tumor cell lines. This study investigates in detail the antitumoral potential of a PPL analogue; (E)-N-(4-fluorobenzyl)-3-(3,4,5-trimethoxyphenyl) acrylamide (NFBTA). The anticancer potential of NFBTA on the glioblastoma multiforme (GBM) cell line (U87MG) was determined by 3-(4,5-dimethyl-2-thia-zolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT), and lactate dehydrogenase (LDH) release analysis, and the selectivity index (SI) was calculated. To detect cell apoptosis, fluorescent staining via flow cytometry and Hoechst 33258 staining were performed. Oxidative alterations were assessed via colorimetric measurement methods. Alterations in expressions of key genes related to carcinogenesis were determined. Additionally, in terms of NFBTA cytotoxic, oxidative, and genotoxic damage potential, the biosafety of this novel agent was evaluated in cultured human whole blood cells. Cell viability analyses revealed that NFBTA exhibited strong cytotoxic activity in cultured U87MG cells, with high selectivity and inhibitory activity in apoptotic processes, as well as potential for altering the principal molecular genetic responses in U87MG cell growth. Molecular docking studies strongly suggested a plausible anti-proliferative mechanism for NBFTA. The results of the experimental in vitro human glioblastoma model and computational approach revealed promising cytotoxic activity for NFBTA, helping to orient further studies evaluating its antitumor profile for safe and effective therapeutic applications.


Assuntos
Acrilamidas/química , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Piperidonas/síntese química , Piperidonas/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dioxolanos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Simulação de Acoplamento Molecular , Piperidonas/química
16.
J Pharm Biomed Anal ; 175: 112770, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31330285

RESUMO

We report a novel amperometric flow-injection (FI) analysis of creatinine based on a sensor comprising copper oxide nanoparticles (CuO) coated with a molecularly-imprinted polymer (CuO@MIP) and decorating a carbon-paste electrode (CPE) to form the CuO@MIP/CPE electrode. The CuO@MIP was synthesized by using CuO as the supporting core, creatinine as the template, methacrylic acid (MAA) as monomer, N, N'-(1,2-dihydroxyethylene)bis(acrylamide) (DHEBA) as cross-linker, and 2,2'-azobis (2-methylpropionitrile) (AIBN) as initiator. Morphology and structural characterization reveal that CuO nanoparticle imprinted sites (CuO) synthesized using a precipitation method, exhibits features that are well suited to creatinine detection: high surface area, good analyte diffusion and adsorption characteristics that provide shorter response times, and large numbers of specific cavities for enhanced analyte capacity and sensitivity. Cyclic voltammetric measurements indicate that our sensor provides excellent performance toward electro-oxidation of creatinine. The amperometric FI system was used to quantitatively determine creatinine at the CuO@MIP/CPE sensor, in a phosphate buffer carrier. The imprinted sensor exhibits excellent performance for creatinine oxidation at an applied potential of +0.35 V and flow rate of 0.6 mL.min-1. The as-prepared sensor exhibits a linear dynamic range for creatinine detection from 0.5 to 200 µM (r2 = 0.995) with a limit of detection of 0.083 µM (S/N = 3). The system exhibits satisfactorily good precision (%RSD = 1.94%, n = 30) and selectivity toward creatinine. There is only approximately 20% loss from initial response after 2 weeks when stored at 4 oC. We successfully applied the FI detection system to detect creatinine in human urine samples.


Assuntos
Carbono/química , Cobre/química , Creatinina/química , Nanopartículas/química , Polímeros/química , Acrilamidas/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Análise de Injeção de Fluxo/métodos , Humanos , Limite de Detecção , Metacrilatos/química , Impressão Molecular/métodos
17.
Colloids Surf B Biointerfaces ; 182: 110347, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31330429

RESUMO

Stimuli-responsive smart polymers have been studied extensively. In this work, thermoresponsive poly (N-isopropylacrylamide-N-methylolacrylamide-acrylamide) (PNIPAm-NMA-Am) was successfully synthesised via radical polymerisation, as confirmed by proton nuclear magnetic resonance and fourier transform infrared spectroscopy. PNIPAm-NMA-Am was electrospun into nanofibres, allowing its use as a drug carrier after simple thermal treatment. Thermogravimetric analysis, scanning electron microscopy, and atomic force microscopy results also revealed that the as-prepared PNIPAm-NMA-Am nanofibres have a uniform small diameter, good thermal stability and excellent integrity in aqueous environments. Additionally, the properties of this PNIPAm-NMA-Am nanofibres were tunable with temperature changes below and above the lower critical solution temperature of 48 °C. The drug release properties of PNIPAm-NMA-Am10 nanofibres as a drug carrier were studied via ultraviolet-visible spectroscopy and the results showed that 80% of the drug was released from the nanofibres after six heating and cooling (60-10 °C) cycles within 60 min. Only a small amount of the drug was released during the cooling process, which directly demonstrates "on-off" functionality of PNIPAm-NMA-Am nanofibres for controlled drug release. Finally, cell culture studies indicated that the PNIPAm-NMA-Am nanofibres have not cytotoxicity. Thus, the novel PNIPAm-NMA-Am nanofibres show great potential in the biomedical field as drug carriers.


Assuntos
Resinas Acrílicas/química , Antineoplásicos/farmacologia , Curcumina/farmacologia , Preparações de Ação Retardada , Portadores de Fármacos , Nanofibras/química , Acrilamidas/química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Técnicas Eletroquímicas , Células HCT116 , Humanos , Cinética , Transição de Fase , Temperatura Ambiente
18.
Eur J Pharm Sci ; 137: 104993, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302214

RESUMO

Therapeutic protein medicines have transformed the treatment of blinding diseases (e.g. age-related macular degeneration, AMD) during the last 1-2 decades. Many blinding conditions such as AMD are chronic; and require multiple intravitreal injections over a long period to achieve a high and reproducible dose needed for clinical benefit. Prolonging the duration of action of ophthalmic drugs is critical to reduce the frequency of injections. Thermoresponsive hydrogels (e.g. N-isopropylacrylamide, NIPAAM) that collapse in physiological conditions can entrap and sustain the release of a therapeutic protein. However, most NIPAAM hydrogels are not biodegradable and often requires invasive surgery to remove the depot. Here, we report the preparation of a hydrogel derived from NIPAAM and acrylated hyaluronic acid (Ac-HA) as a biodegradable, macromolecular crosslinker. Ac-HA was prepared by the acrylation of hyaluronic acid (HA). Antibody (infliximab (INF), 5.0 mg/mL or bevacizumab (BEVA), 12.5 mg/mL), NIPAAM (0.35 mmol) and Ac-HA (2.0-10.0 mg/mL, 40.0-200.0 nmol) were first mixed prior to redox polymerisation to ensure maximal protein mixing and to shorten the burst release. Hydrogels with lower amounts of Ac-HA (2.0-4.0 mg/mL, 40.0-80.0 nmol) showed favourable lower critical solution temperature (LCST) values and injectability (27-29G) than higher amounts of Ac-HA (>4.0 mg/mL, >80.0 nmol). These hydrogels were further characterised (swelling ratio (SR), water retention (WR) and rheology). All hydrogels degraded in presence of bovine testes hyaluronidase (0-50 U/mL, 37 °C, 100 rpm). Release studies of BEVA-loaded hydrogels were investigated in vitro using the PK-Eye™ model, which estimates the human clearance times of proteins from the back of the eye. Phosphate buffered saline (PBS, pH 7.4, 37 °C) was used rather than simulated vitreous to more effectively map trends between the formulations. A zero-order release profile was observed between days 5 to 50 with 43.3 ±â€¯9.5% protein released at day 50. Determining protein binding and functionality from a formulation is crucial to determine the optimal formulation prior to more detailed studies that might be necessary. BEVA showed binding to human vascular growth endothelial factor (VEGF165) throughout the study (two months) while still maintaining a therapeutic dose (123.5 ±â€¯45.6 ng) in the posterior cavity of the PK-Eye™ model. These encouraging results suggest that extended release of proteins in the vitreous can be achieved using injectable hydrogels derived from NIPAAM and HA.


Assuntos
Acrilamidas/administração & dosagem , Inibidores da Angiogênese/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Bevacizumab/administração & dosagem , Ácido Hialurônico/administração & dosagem , Hidrogéis/administração & dosagem , Infliximab/administração & dosagem , Acrilamidas/química , Anti-Inflamatórios/química , Bevacizumab/química , Olho/metabolismo , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/química , Hidrogéis/química , Infliximab/química , Injeções Intravítreas , Modelos Biológicos
19.
Colloids Surf B Biointerfaces ; 182: 110355, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306828

RESUMO

Inspired by the excellent membrane affinity of antimicrobial polymers, we synthesized a novel biodegradable poly(amino amine) polymer with pendent side chains that mimic the widely used biocide polyhexamethylene biguanide (PHMB) for gene delivery. Michael addition polymerization was utilized to form the polymer scaffold between N,N'-cystaminebisacrylamide (CBA) and N-Boc-1,6-diaminohexane (Boc-DAH) followed by N-Boc deprotection. Then the exposed primary amino groups were partly (about 75%) transformed into biguanide by an addition reaction with dicyandiamide to obtain the final product CBA-DAH-biguanide (CBA-DAH-BG). The polymer CBA-DAH-BG was able to condense plasmid DNA (pDNA) into nano-sized (<200 nm), positively-charged (>35 mV) polyplexes that were well resistant to heparin and DNase I. Rapid DNA release was observed in the presence of dithiothreitol (DTT), indicating that CBA-DAH-BG was equipped with biodegradability by the cleavage of disulfide bonds, which was helpful for unpacking DNA and decreasing cytotoxicity. CBA-DAH-BG/pDNA polyplexes were characterized by efficient cellular uptake efficacy, extremely low cytotoxicity, and high transfection efficiency in two cell lines (i.e., NIH/3T3 and U87 MG), compared to 25 kDa polyethyleneimine (PEI) and the intermediate product CBA-DAH that were both devoid of biguanide groups. Of note, clathrin-mediated endocytosis and lipid rafts played an important role in the internalization of the polyplexes. Taken together, this strategy described herein may represent an innovative avenue for the design of more advanced nonviral gene vectors with high transfection efficiency and biocompatibility.


Assuntos
Anti-Infecciosos/síntese química , Biguanidas/síntese química , Técnicas de Transferência de Genes , Plasmídeos/metabolismo , Polietilenoimina/química , Acrilamidas/química , Animais , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Biguanidas/metabolismo , Biguanidas/farmacologia , Linhagem Celular Tumoral , Desoxirribonuclease I/química , Diaminas/química , Ditiotreitol/química , Endocitose , Genes Reporter , Heparina/química , Hexanos/química , Humanos , Hidrólise , Luciferases/genética , Luciferases/metabolismo , Camundongos , Células NIH 3T3 , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Plasmídeos/química , Polietilenoimina/toxicidade
20.
Carbohydr Polym ; 222: 114979, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31320049

RESUMO

The release attributes of anticancer therapeutic embedded in programmable gum ghatti hydrogel matrices has been evaluated. Hydrogel has been programmed simply by adjusting the product composition (monomer-acrylamide and crosslinker- N, N Methylenebisacrylamide (MBAm)) to control mesh size during copolymerization of gum through microwave based technique. The synthesized system has been characterized for physicochemical traits and 'in-vitro' drug release in various physiological pH conditions by USP standard method. The degree of crosslinking analysed through equilibrium swelling ratio (ESR) has been correlated with release kinetics. The release profiles yielded from the measurements of cumulative drug delivery showed that the system with lower ESR included slower release rate than that of the system with higher ESR, consequently generated higher t50 values. Additionally, the release rate rises with rise in pH milieu.


Assuntos
Portadores de Fármacos/química , Liberação Controlada de Fármacos , Fluoruracila/administração & dosagem , Hidrogéis/química , Gomas Vegetais/química , Acrilamidas/química , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Micro-Ondas , Polimerização
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