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1.
AAPS PharmSciTech ; 22(5): 182, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129146

RESUMO

The oral bioavailability of curcumin is limited, attributed to its low solubility or dissolution and poor absorption. Herein, the study describes formulation of curcumin-loaded mixed micelles of Gelucire® 48/16 and TPGS for its dissolution rate enhancement. Curcumin was dispersed in these molten lipidic surfactants which was then adsorbed on carrier and formulated as pellets by extrusion spheronization. Critical micelle concentration (CMC) of binary mixture of Gelucire® 48/16 and TPGS was lower than their individual CMC demonstrating the synergistic behavior of mixture. Thermodynamic parameters like partition coefficient and Gibbs free energy of solubilization indicated that mixed micelles were more efficient than micelles of its individual components in curcumin solubilization. Dynamic light scattering (DLS) suggested slight increase in micellar size of mixed micelles than its components suggesting curcumin loading in mixed micelles. Fourier transform infrared spectroscopy (FTIR) revealed that phenolic hydroxyl group interacts with lipids which contribute to its enhanced solubility. Furthermore, the differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study indicated the conversion of crystalline curcumin into amorphous form. In the pellet formulation, Gelucire® 48/16 acted as a binder and eliminated the requirement of additional binder. Microcrystalline cellulose (MCC) forms wet mass and retards the release of curcumin from pellets. Increase in concentration of water-soluble diluent increased drug release. The optimized formulation released more than 90% drug and maintains supersaturation level of curcumin for 2 h. Thus, mixed micellar system was effective delivery system for curcumin while pellet formulation is an interesting formulation strategy consisting semi-solid lipids.


Assuntos
Curcumina/síntese química , Micelas , Polietilenoglicóis/síntese química , Ácidos Polimetacrílicos/síntese química , Vitamina E/síntese química , Disponibilidade Biológica , Curcumina/farmacocinética , Portadores de Fármacos/síntese química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Excipientes/síntese química , Excipientes/farmacocinética , Polietilenoglicóis/farmacocinética , Ácidos Polimetacrílicos/farmacocinética , Solubilidade , Vitamina E/farmacocinética , Difração de Raios X/métodos
2.
Methods Mol Biol ; 2147: 45-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32840809

RESUMO

Thanks to their unique advantages, additive manufacturing technologies are revolutionizing almost all sectors of the industrial and academic worlds, including tissue engineering and regenerative medicine. In particular, 3D bioprinting is rapidly emerging as a first-choice approach for the fabrication-in one step-of advanced cell-laden hydrogel constructs to be used for in vitro and in vivo studies. This technique consists in the precise deposition layer-by-layer of sub-millimetric hydrogel strands in which living cells are embedded. A key factor of this process consists in the proper formulation of the hydrogel precursor solution, the so-called bioink. Ideal bioinks should be able, on the one side, to support cell growth and differentiation and, on the other, to allow the high-resolution deposition of cell-laden hydrogel strands. The latter feature requires the extruded solution to instantaneously undergo a sol-gel transition to avoid its collapse after deposition.To address this challenge, researchers are recently focusing their attention on the synthesis of several derivatives of natural biopolymers to enhance their printability. Here, we present an approach for the synthesis of photocurable derivatives of natural biopolymers-namely, gelatin methacrylate, hyaluronic acid methacrylate, chondroitin sulfate methacrylate, and PEGylated fibrinogen-that can be used to formulate tailored innovative bioinks for coaxial-based 3D bioprinting applications.


Assuntos
Biopolímeros/química , Bioimpressão/métodos , Ácidos Polimetacrílicos/síntese química , Impressão Tridimensional , Tecidos Suporte/química , Biopolímeros/efeitos da radiação , Bioimpressão/instrumentação , Sulfatos de Condroitina/química , Fibrinogênio/química , Gelatina/química , Humanos , Ácido Hialurônico/química , Hidrogéis/química , Tinta , Luz , Processos Fotoquímicos , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Propriedades de Superfície/efeitos da radiação , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
3.
J Chromatogr A ; 1628: 461481, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32822998

RESUMO

A single-step copolymerization strategy was developed for the preparation of carbohydrate (glucose and maltose) functionalized monoliths using click reaction. Firstly, novel carbohydrate-functionalized methacrylate monomers were synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (alkyne-azide reaction) of terminal alkyne with azide of carbohydrate derivatives. The corresponding carbohydrate functionalized monolithic columns were then prepared through a single-step in-situ copolymerization. The physicochemical properties and performance of the fabricated monolithic columns were evaluated using scanning electron microscopy, Fourier-transform infrared spectroscopy, and nano-liquid chromatography. For the optimized monolithic column, satisfactory column permeability and good separation performance were demonstrated for polar compounds including nucleoside, phenolic compounds and benzoic acid derivatives. The monolithic column is also highly useful for selective and efficient enrichment of glycopeptides from human IgG tryptic digests. This study not only provided a novel hydrophilic column for separation and selective trapping of polar compounds, but also proposed a facile and efficient approach for preparing carbohydrate functionalized monoliths.


Assuntos
Carboidratos/química , Química Click/métodos , Carboidratos/síntese química , Glicopeptídeos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Polimerização , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
4.
Carbohydr Polym ; 236: 116021, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172841

RESUMO

In this work, a facile click reaction strategy is employed to form hydrogels in situ with cytocompatibility, biodegradability, self-healing property and resistance to protein. The thiol-functionalized zwitterionic carboxybetaine methacrylate copolymer, which take part as a cross-linker in the "thiol-ene" click reaction with the methacrylated hyaluronic acid. The hydrogels are obtained under the physiological condition without the presence of any copper catalyst and UV light. The hydrogel consisting of zwitterionic component shows an obvious reduction in protein adsorption and cell adhesion and avoid non-targeted factor interference in the biological experiments. The hydrogels also demonstrate adjustable degradation behavior. Human mesenchymal stem cells (hMSCs) are easily encapsulated into the hydrogels and remains metabolically active, indicating the excellent biocompatibility of the hydrogels. Additionally, the result of the cytokine secretion assays (IL-6 and TNF-α) has shown that this clickable hydrogel can serve to suppress inflammatory reactions and is beneficial for in vivo applications. Based on the above results, this clickable hydrogel with excellent performance can be an amenable platform for 3D cell encapsulation.


Assuntos
Ácido Hialurônico/análogos & derivados , Hidrogéis/química , Ácidos Polimetacrílicos/química , Compostos de Sulfidrila/química , Animais , Adesão Celular/efeitos dos fármacos , Encapsulamento de Células/métodos , Sobrevivência Celular/efeitos dos fármacos , Química Click , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Interleucina-6/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/toxicidade , Células RAW 264.7 , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/toxicidade , Fator de Necrose Tumoral alfa/metabolismo
5.
Anal Chim Acta ; 1093: 160-167, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31735210

RESUMO

In this study, poly(butyl methacrylate-co-ethyleneglycol dimethacrylate) polymeric monoliths were in situ developed within 0.75 mm i.d. poly(ethylene-co-tetrafluoroethylene) (ETFE) tubing by UV polymerization via three different free-radical initiators (α,α'-azobisisobutyronitrile (AIBN), 2,2-dimethoxy-2-phenylacetophenone (DMPA) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMPP). The influence of the nature of each photo-initiator and irradiation time on the morphological features of the polymer was investigated by scanning electron microscopy, and the chromatographic properties of the resulting microbore columns were evaluated using alkyl benzenes as test substances. The beds photo-initiated with MTMPP gave the best performance (minimum plate heights of 38 µm for alkyl benzenes) and exhibited a satisfactory reproducibility in the chromatographic parameters (RSD < 11%). These monolithic columns were also successfully applied to the separation of phenylurea herbicides, proteins and a tryptic digest of ß-casein.


Assuntos
Acetofenonas/química , Cromatografia Líquida de Alta Pressão/instrumentação , Morfolinas/química , Nitrilas/química , Ácidos Polimetacrílicos/química , Politetrafluoretileno/análogos & derivados , Propiofenonas/química , Acetofenonas/efeitos da radiação , Caseínas/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Herbicidas/isolamento & purificação , Metacrilatos/química , Morfolinas/efeitos da radiação , Nitrilas/efeitos da radiação , Fragmentos de Peptídeos/isolamento & purificação , Compostos de Fenilureia/isolamento & purificação , Polimerização , Ácidos Polimetacrílicos/síntese química , Politetrafluoretileno/química , Propiofenonas/efeitos da radiação , Raios Ultravioleta
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 225: 117447, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31454688

RESUMO

Bio-degradable/bio-compatible poly(lactide-co-glycidyl methacrylate), P(LA-co-GMA), a copolymer has been synthesized. The material contains curable CC groups, which enable its self-curing and grafting reactions with other vinyl monomers. The copolymer was grafted with a pH-responsive polyacrylamide (PAAm), by UV-assisted reactions using acrylamide (AAm) and N,N'-methylene bisacrylamide monomers, and various photoinitiator systems. The original copolymer and its partially-cured counterpart were employed in the grafting reaction. Chemical structures and properties of the resulting materials were characterized. Standard quantitative analysis techniques for measurement of the grafted AAm content and the degree of CC conversion have been developed by 1H NMR and FTIR spectroscopy. FTIR offers more advantages, in terms of non-destructive analysis, ease of operation, and lower cost of analysis. The results show that the grafted products from pre-cured P(LA-co-GMA) copolymers contain higher grafted AAm contents than their uncured counterparts. The highest grafted AAm content was obtained by using benzophenone (BP) as an initiator, while camphorquinone (CQ) led to the lowest content. In contrast, the degree of CC conversion of the copolymer from the two initiator systems shows a reverse trend. These amphiphilic and pH-responsive grafted copolymers with tunable AAm contents have a high potential for use in various applications, especially in biomedical and environmental fields.


Assuntos
Plásticos Biodegradáveis/síntese química , Polímeros/síntese química , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Plásticos Biodegradáveis/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Poliésteres/síntese química , Poliésteres/química , Polímeros/química , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/síntese química , Tensoativos/química
7.
Eur J Pharmacol ; 866: 172804, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31738938

RESUMO

Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3-1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties.


Assuntos
Acitretina/química , Metotrexato/química , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/toxicidade , Psoríase/tratamento farmacológico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Humanos , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/uso terapêutico , Pele/efeitos dos fármacos
8.
Curr Drug Deliv ; 16(6): 548-564, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31577200

RESUMO

OBJECTIVE: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs. METHOD: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels. RESULTS: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group. CONCLUSION: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.


Assuntos
Materiais Biocompatíveis/química , Colo/metabolismo , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Losartan/metabolismo , Ácidos Polimetacrílicos/química , Acrilatos/administração & dosagem , Acrilatos/química , Administração Oral , Animais , Materiais Biocompatíveis/síntese química , Colo/química , Liberação Controlada de Fármacos , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Losartan/química , Ácidos Polimetacrílicos/administração & dosagem , Ácidos Polimetacrílicos/síntese química , Coelhos
9.
Anal Chim Acta ; 1089: 78-89, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31627821

RESUMO

Novel molecularly imprinted polymer (MIP) for metformin was synthesized on the surface of magnetic multi-walled carbon nanotubes (MMWCNTs) as the support. Metformin was used as the template, methacrylic acid (MAA) as the functional monomer, ethylene glycol dimethacrylate (EGDMA) as the cross-linker and 2,2'-azoisobutyronitrile (AIBN) as the initiator. The synthesized composite was characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FTIR). The surface molecularly imprinted composite was used for magnetic solid phase microextraction (MSPME) of metformin before its chemiluminescence (CL) determination and its capability was compared with non-imprinted polymer (NIP). The central composite design was used for optimization as well as consideration of possible interaction of effective variables on extraction. Under the optimized conditions, the developed method exhibited the linear dynamic range of 0.5-50.0 µg L-1 with a detection limit of 0.13 µg L-1 and enhancement factor of 195.3 for the preconcentration of 100 mL of the sample and 500 µL of an eluent. The intra- and inter-day relative standard deviations (RSD%) at 5.0 µg L-1 level of metformin (n = 6) were 3.7 and 4.9%, respectively. The maximum adsorption capacity of the sorbent was found to be 80.0 mg g-1, the adsorption of metformin was endothermic and spontaneous and followed the Langmuir isotherm model. The adsorption kinetic was also found to be best fitted with the pseudo-second-order model. The designed method was successfully applied to the extraction and determination of metformin in biological fluids and water samples.


Assuntos
Metformina/análise , Nanotubos de Carbono/química , Microextração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Adsorção , Água Potável/análise , Cinética , Limite de Detecção , Metformina/sangue , Metformina/urina , Impressão Molecular , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Água do Mar/análise , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/urina
10.
Small ; 15(42): e1903784, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31448570

RESUMO

Biodegradable polycaprolactone (PCL) has been widely applied as a scaffold material in tissue engineering. However, the PCL surface is hydrophobic and adsorbs nonspecific proteins. Some traditional antifouling modifications using hydrophilic moieties have been successful but inhibit cell adhesion, which is not ideal for tissue engineering. The PCL surface is modified with bioinspired zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) via surface-initiated atom transfer radical polymerization to improve cell adhesion through the unique interaction between choline phosphate (CP, on PMCP) and phosphate choline (PC, on cell membranes). The hydrophilicity of the PCL surface is significantly enhanced after surface modification. The PCL-PMCP surface reduces nonspecific protein adsorption (e.g., up to 91.7% for bovine serum albumin) due to the zwitterionic property of PMCP. The adhesion and proliferation of bone marrow mesenchymal stem cells on the modified surface is remarkably improved, and osteogenic differentiation signs are detected, even without adding any osteogenesis-inducing supplements. Moreover, the PCL-PMCP films are more stable at the early stage of degradation. Therefore, the PMCP-functionalized PCL surface promotes cell adhesion and osteogenic differentiation, with an antifouling background, and exhibits great potential in tissue engineering.


Assuntos
Incrustação Biológica , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosforilcolina/análogos & derivados , Poliésteres/farmacologia , Ácidos Polimetacrílicos/farmacologia , Engenharia Tecidual , Adsorção , Animais , Animais Recém-Nascidos , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Fosforilcolina/síntese química , Fosforilcolina/farmacologia , Espectroscopia Fotoeletrônica , Poliésteres/síntese química , Ácidos Polimetacrílicos/síntese química , Ratos Sprague-Dawley , Propriedades de Superfície , Água/química
11.
Analyst ; 144(14): 4320-4330, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31192335

RESUMO

Restricted access molecularly imprinted polymers (RAMIPs) are hybrid materials that present selective binding sites for a template (or similar molecules), and an external hydrophilic layer that avoids the binding of proteins to the material, making them appropriate for the sample preparation of protein fluids. RAMIPs have been used successfully in online and offline solid phase extractions, but there is no application as a fiber in solid phase microextraction (SPME), to the best of our knowledge. In this paper, molecularly imprinted fibers were synthesized inside glass capillary tubes (0.53 mm i.d.), using diazepam and methacrylic acid as template and functional monomer, respectively. The MIP fibers were coated with a cross-linked bovine serum albumin (BSA) layer, resulting in RAMIP fibers that were used in the SPME of benzodiazepines directly from biological fluids. The BSA layer acts as a protective barrier that avoids the binding of proteins from the sample by an electrostatic repulsion mechanism. The protein exclusion capacity of the RAMIP fiber was about 98%, which is selective to benzodiazepines in comparison with other drugs (citalopram and fluoxetine). The SPME was optimized and the extraction conditions were set as follows: 1000 µL of the sample diluted with water (1 : 0.5, v : v), no pH adjustment, an extraction time of 20 min at 500 rpm, and elution with 200 µL of acetonitrile for 5 min at 500 rpm. The fibers were used in the SPME of benzodiazepines directly from plasma samples, followed by HPLC-DAD analyses. The method was linear for bromazepam (50-750 µg L-1), clonazepam (15-250 µg L-1), alprazolam (15-350 µg L-1), nordiazepam (100-2100 µg L-1) and diazepam (100-2600 µg L-1), with correlation coefficients higher than 0.97. Relative standard deviations (precision) and relative errors (accuracy) ranged from 0.5 to 20.0%, and -15.6 to 21.6%, respectively.


Assuntos
Benzodiazepinas/sangue , Ácidos Polimetacrílicos/química , Adsorção , Animais , Benzodiazepinas/química , Bovinos , Diazepam/química , Humanos , Cinética , Metacrilatos/química , Impressão Molecular/métodos , Ácidos Polimetacrílicos/síntese química , Estudo de Prova de Conceito , Soroalbumina Bovina/química , Microextração em Fase Sólida/instrumentação , Microextração em Fase Sólida/métodos
12.
Biomacromolecules ; 20(6): 2265-2275, 2019 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-31042022

RESUMO

Poly(2-methoxyethyl acrylate) (PMEA) shows excellent blood compatibility because of the existence of intermediate water. Various modifications of PMEA by changing its main or side chain's chemical structure allowed tuning of the water content and the blood compatibility of numerous novel polymers. Here, we exploit a possibility of manipulating the surface hydration structure of PMEA by incorporation of small amounts of hydrophobic fluorine groups in MEA polymers using atom-transfer radical polymerization and the (macro) initiator concept. Two kinds of fluorinated MEA polymers with similar molecular weights and the same 5.5 mol % of fluorine content were synthesized using the bromoester of 2,2,3,3,4,4,5,5,6,6,7,7,8,8-pentadecafluoro-1-octanol (F15) and poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA) as (macro) initiators, appearing liquid and solid at room temperature, respectively. The fibrinogen adsorption of the two varieties of fluorinated MEA polymers was different, which could not be explained only by the bulk hydration structure. Both polymers show a nanostructured morphology in the hydrated state with different sizes of the features. The measured elastic modulus of the domains appearing in atomic force microscopy and the intermediate water content shed light on the distinct mechanism of blood compatibility. Contact angle measurements reveal the surface hydration dynamics-while in the hydrated state, F15- b-PMEA reorients easily to the surface exposing its PMEA part to the water, the small solid PTFEMA block with high glass-transition temperature suppresses the movement of PTFEMA- b-PMEA and its reconstruction on the surface. These findings illustrate that in order to make a better blood compatible polymer, the chains containing sufficient intermediate water need to be mobile and efficiently oriented to the water surface.


Assuntos
Materiais Biocompatíveis/síntese química , Plaquetas , Fibrinogênio/química , Ácidos Polimetacrílicos/síntese química , Adsorção , Materiais Biocompatíveis/química , Halogenação , Humanos , Nanoestruturas/química , Ácidos Polimetacrílicos/química , Água/química
13.
Nat Chem ; 11(6): 578-586, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30988414

RESUMO

Polymerization reactions conducted inside cells must be compatible with the complex intracellular environment, which contains numerous molecules and functional groups that could potentially prevent or quench polymerization reactions. Here we report a strategy for directly synthesizing unnatural polymers in cells through free radical photopolymerization using a number of biocompatible acrylic and methacrylic monomers. This offers a platform to manipulate, track and control cellular behaviour by the in cellulo generation of macromolecules that have the ability to alter cellular motility, label cells by the generation of fluorescent polymers for long-term tracking studies, as well as generate a variety of nanostructures within cells. It is remarkable that free radical polymerization chemistry can take place within such complex cellular environments. This demonstration opens up a multitude of new possibilities for how chemists can modulate cellular function and behaviour and for understanding cellular behaviour in response to the generation of free radicals.


Assuntos
Radicais Livres/química , Polimerização/efeitos da radiação , Ácidos Polimetacrílicos/síntese química , Poliestirenos/síntese química , Acrilatos/química , Acrilatos/efeitos da radiação , Acrilatos/toxicidade , Citoesqueleto de Actina/efeitos dos fármacos , Compostos de Anilina/química , Compostos de Anilina/efeitos da radiação , Compostos de Anilina/toxicidade , Movimento Celular/efeitos dos fármacos , Fluorescência , Células HeLa , Humanos , Metacrilatos/química , Metacrilatos/efeitos da radiação , Metacrilatos/toxicidade , Propano/análogos & derivados , Propano/química , Propano/efeitos da radiação , Fase S/efeitos dos fármacos , Estirenos/química , Estirenos/efeitos da radiação , Estirenos/toxicidade , Raios Ultravioleta , Compostos de Vinila/química , Compostos de Vinila/efeitos da radiação , Compostos de Vinila/toxicidade
14.
J Mech Behav Biomed Mater ; 94: 222-228, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30921729

RESUMO

Two dimethacrylate oligomers named polypropylenglycol bis(2-hydroxy-3-methoxypropyl) dimethacrylates (380PPMA and 640PPMA) with different molecular weight were synthesized through ring opening addition reaction between epoxy terminated oligomers PPDE and methacrylic acid, and their structures were confirmed by FT-IR and 1H-NMR spectra. The PPMAs were used to replace TEGDMA partially in Bis-GMA/TEGDMA (50/50, wt./wt.) with the aim to reducing volumetric shrinkage and shrinkage stress of dental resin composites. Dental resin composite without PPMAs was used as control. Double bond conversion (DC), volumetric shrinkage (VS), shrinkage stress, water sorption (WS) and solubility (SL), flexural strength (FS) and modulus (FM) of experimental dental resin composites were investigated. Dynamic mechanical analysis (DMA) was used to evaluate the glass transition temperature (Tg), heterogeneity, and crosslink density (υ). The results showed that dental resin composites contained 640PPMA had slower polymerization rate. Only dental resin composites with 20 wt% of 640PPMA in resin matrix had lower VS than control group (p < 0.05). All of PPMAs containing composites had lower shrinkage stress than control group (p < 0.05). Before water immersion, all of experimental dental resin composites had the same FS and FM (p > 0.05), while after water immersion, FM of dental resin composites with PPMAs became lower than control (p < 0.05). Higher WS and SL were observed in composites with 640PPMA (p < 0.05). Incorporation of PPMAs into dental resin composites could decrease Tg and crosslink density (p < 0.05), but more homogeneous materials could be obtained (p < 0.05). Therefore, PPMAs could be used to reduce volumetric shrinkage and shrinkage stress of dental resin composites, but further studies concerned biocompatibility and service life should be taken because of the higher WS and SL.


Assuntos
Resinas Acrílicas/química , Resinas Compostas/química , Ácidos Polimetacrílicos/química , Poliuretanos/química , Estresse Mecânico , Teste de Materiais , Ácidos Polimetacrílicos/síntese química , Solubilidade , Água/química
15.
J Am Chem Soc ; 141(7): 3100-3109, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30674187

RESUMO

Polymer brush coatings are frequently prepared by radical polymerization, a notoriously oxygen sensitive process. Glucose oxidase (GOx) can inexpensively enable radical polymerization in solution by enzymatically consuming oxygen as it oxidizes glucose. Here, we report the growth of polymeric brushes using GOx-assisted atom transfer radical polymerization (ATRP) from a surface while open to air. Specifically, we grew a set of biomedically relevant polymer brushes, including poly(oligo(ethylene glycol) methacrylate) (POEGMA), poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), poly(sulfobetaine methacrylate) (PSBMA), and poly(2-(methylsulfinyl)ethyl acrylate (PMSEA). For each of these polymers, we monitored GOx-assisted and GOx-free ATRP reaction kinetics in real time using quartz crystal microbalance (QCM) and verified findings with localized surface plasmon resonance (LSPR). We modeled brush growth kinetics considering bimolecular termination. This model fit our data well ( r2 > 0.987 for all samples) and shows the addition of GOx increased effective kinetic chain lengths, propagation rates, and reproducibility. We tested the antifouling properties of the polymer brush coatings against human blood plasma and were surprised to find that coatings prepared with GOx repelled more plasma proteins in all cases than their GOx-free counterparts.


Assuntos
Glucose Oxidase/química , Ácidos Polimetacrílicos/síntese química , Incrustação Biológica/prevenção & controle , Glucose/química , Humanos , Oxigênio/química , Plasma/química , Polimerização , Técnicas de Microbalança de Cristal de Quartzo , Ressonância de Plasmônio de Superfície
16.
Carbohydr Polym ; 207: 628-639, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30600048

RESUMO

Here, we report synthesis of a terpolymeric covalently crosslinked hydrogel of hyaluronate (HA) as biomaterial with elasticity, mechanical properties and cell interactions via conventional free radical polymerization technique. To provide elasticity and mechanical properties, 2-hydroxyethyl acrylate (HEA) was grafted in HA, while to tune cellular interactions, gelatin methacryloyl (GM) was used as crosslinker. The composition and probable structure of the terpolymer (HA-g-pHEA-x-GM) were analysed by FTIR, 1H HR-MAS-NMR, and TGA analyses. The SEM and texture analyses of hydrogel showed interconnected micro-porous network and high mechanical properties, respectively. In vitro biocompatibility was studied against human chondrocytes, whereas, in vivo biocompatibility and tissue regeneration were confirmed using mouse model. The hydrogel releases model protein-bovine serum albumin, and corticosteroid drug-dexamethasone in a sustain way at pH 7.4 and 37 °C. Overall, the tunable mechanical properties, micro-porous network, and cytocompatibility of the HA-g-pHEA-x-GM hydrogel highlights its potential applicability in cartilage tissue engineering and drug delivery.


Assuntos
Materiais Biocompatíveis/química , Gelatina/química , Ácido Hialurônico/química , Hidrogéis/química , Ácidos Polimetacrílicos/química , Animais , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/toxicidade , Bovinos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Dexametasona/química , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Elasticidade , Gelatina/síntese química , Gelatina/toxicidade , Humanos , Ácido Hialurônico/síntese química , Ácido Hialurônico/toxicidade , Hidrogéis/síntese química , Hidrogéis/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Polimerização , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/toxicidade , Porosidade , Soroalbumina Bovina/química
17.
J Mater Chem B ; 7(11): 1875-1881, 2019 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-32255050

RESUMO

A fluorescent amino poly(glycidyl methacrylate) (PGOHMA) was synthesized by atom transfer radical polymerization (ATRP) and post-polymerization. The obtained star polymer PGOHMA has eight polymer arms enriched with amine groups for gene delivery. PGOHMA showed much lower cytotoxicity and higher delivery efficiency, compared with the widely used commercial and previously reported gene carriers. Therefore, a new star-shaped fluorescent polymer was successfully synthesized and explored as an efficient gene carrier.


Assuntos
Técnicas de Transferência de Genes , Ácidos Polimetacrílicos , Fluorescência , Terapia Genética/métodos , Células HeLa , Humanos , Imagem Óptica/métodos , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia
18.
Curr Org Synth ; 16(7): 1002-1009, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31984881

RESUMO

BACKGROUND: Presently, rise in the infectious diseases and subsequent development of drug resistance, is a global threat to human health. However, much efforts are being made by scientists, to develop novel antimicrobials, and also to improve the efficacy of available drugs, in order to combat the lifethreatening infections. OBJECTIVE: Synthesis and characterization of azole functional polymer systems for antimicrobial applications. MATERIALS AND METHODS: Poly(glycidyl methacrylate) (PGMA), was produced by free radical polymerization of the monomer, glycidyl methacrylate (GMA). Different azole functional PGMAs were produced, through chemical modification with imidazole (Im), 1H-1,2,4-triazole (Tri) and 3-amino-1,2,4-triazole (ATri), to get PGMA-Imi, PGMA-Tri and PGMA-ATri, respectively. The structure was confirmed by Fourier transform infrared spectroscopy (FT-IR), thermal properties were investigated by Thermogravimetric Analysis (TGA), and surface morphology was studied by scanning electron microscopy (SEM). Newly synthesized derivatives were further explored, for their antibacterial and anticandidal activities. RESULTS: All the three synthesized and characterized derivatives, displayed a significant activity against the tested microorganisms. The minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC), recorded against Staphylococcus aureus (S. aureus), was 0.5 &1mg/ml for PGMA-Imi, followed by PGMA-ATri & PGMA-Tri, respectively, followed by E. coli with, 1 & 2 mg/ml, 4 & 8 mg/ml, 4& 8 mg/ml, respectively, whereas the maximum MIC & MFC was recorded against C. albicans i.e., 8 & 16 mg/ml, 4 & 8 mg/ml ,4 & 8 mg/ml for PGMA-ATri, PGMA-Tri, PGMA-Imi, respectively. CONCLUSION: In the present work, we report on the state-of-the-art, azole functional polymer systems for antimicrobial applications. These findings suggest that the synthesized azole functional polymer films have antimicrobial properties, which could be potential candidates for coating applications in the biomedical and wastewater treatment field.


Assuntos
Antibacterianos/síntese química , Antifúngicos/síntese química , Azóis/síntese química , Ácidos Polimetacrílicos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Azóis/química , Azóis/farmacologia , Infecções Bacterianas/prevenção & controle , Candida albicans/efeitos dos fármacos , Candidíase/prevenção & controle , Técnicas de Química Sintética , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Águas Residuárias/microbiologia
19.
Macromol Rapid Commun ; 40(2): e1800331, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29974536

RESUMO

The evolution of particle morphology occurring during polymerization-induced self-assembly (PISA) of a block copolymer poly(oligo(ethylene glycol) methacrylate)-b-poly(benzyl methacrylate) (POEGMA-b-PBzMA) is studied. A well-controlled reversible addition-fragmentation chain transfer (RAFT) polymerization yields nano-objects with various morphologies: spheres, aggregates, worm-like structures, and vesicles. A comparison of the morphology of the nano-objects formed from two different chain-length stabilizers established that the unreacted monomer played an important role during the morphology transitions, which is contrary to previous observations. In addition, morphology evolution to higher-order structures could be attained simply by extending the reaction time, after reaching full monomer conversion.


Assuntos
Técnicas de Química Sintética/métodos , Nanopartículas/química , Polimerização , Ácidos Polimetacrílicos/química , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Ácidos Polimetacrílicos/síntese química
20.
Langmuir ; 35(5): 1391-1403, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30134095

RESUMO

A procedure for the preparation of copolymers bearing sulfobetaine and carboxybetaine methacrylic-based monomers by free-radical polymerization is described and discussed. A combination of monomers affects the upper critical solution temperature (UCST) in water and in the presence of a simple NaCl electrolyte while retaining the zwitterionic character. In addition, hydrogel samples were prepared and showed tunable water structure and mechanical properties. The total nonfreezable water content decreases with the amount of carboxybetaine segment in the hydrogel feed and the compression moduli were in a range of 0.7-1.6 MPa. Responses to external conditions such as temperature and ion strength were investigated and a potential application such as modulated thermal detection is proposed. The presence of the carboxylate group in the carboxybetaine segment enables a small fluorescence probe and peptide bearing RDG motif to be attached to polymer and hydrogel samples, respectively. The hydrogel samples functionalized with the RGD motif exhibit controlled cell adhesion. Such synthetic strategy based on combination of different zwitterionic segments offers a simple pathway for the development of zwitterionic materials with programmable properties.


Assuntos
Adesão Celular/efeitos dos fármacos , Ácidos Polimetacrílicos/farmacologia , Água/química , Células 3T3 , Animais , Betaína/análogos & derivados , Betaína/química , Hidrogéis/síntese química , Hidrogéis/química , Hidrogéis/farmacologia , Concentração de Íons de Hidrogênio , Camundongos , Concentração Osmolar , Polimerização , Ácidos Polimetacrílicos/síntese química , Ácidos Polimetacrílicos/química , Temperatura de Transição , Substâncias Viscoelásticas/síntese química , Substâncias Viscoelásticas/química , Substâncias Viscoelásticas/farmacologia
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