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1.
ACS Omega ; 8(43): 40110-40118, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37929110

RESUMO

Thermoplastic polymers have many desirable properties for consumer applications and are complemented by efficient thermal processing techniques, reducing the cost of manufacturing. Lignin exists as an immense biobased carbon source but has largely been researched for its use in thermoset materials due to its own cross-linked, polyfunctional nature. In this study, a new reaction design is employed to create a thermoplastic polyamide network incorporating lignin that is tested to be 99% biobased carbon by radiocarbon analysis. Chemical analysis reveals the nature of lignin incorporation based on chain extension and cross-linking models. The thermal and rheological properties of the new polymers are thoroughly investigated to demonstrate the higher melt-strength capability of the lignin-based polymers facilitating their use in modern processing equipment. This analysis results in finding an optimal lignin loading ratio in the polymer composition reflected by improved tensile strength and stiffness. The results point to a promising polymer design for applying industrial kraft lignin in high-value thermoplastic polymer applications.

2.
Sci Rep ; 12(1): 1017, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35046449

RESUMO

In the present work, polymeric cages with 18 different pocket geometries are developed to investigate the effects of geometrical parameters and material properties on the amount of roller push-out force. An experimental setup including a specialized injection molding tool is designed and fabricated and three sets of polymeric cages are manufactured using the selected materials (PA46, PA66, PPA). Force measurements are carried out five times on each pocket and three cages for each material are tested. Considering three different materials, a total of 810 force measurements are performed. A theoretical model is developed to predict the roller push-out forces in polymeric cages with different materials and pocket geometries. The model is developed by estimating the deformed region of the cage as a cantilever beam with a parabolic profile. An empirical coefficient is reposed in the model to compensate for the assumptions applied to the model. Experimental results showed that a fixed coefficient gives accurate results for all the geometries and materials, which confirms the validity of the approach adopted in this paper for modeling such problems. Considering the geometrical and material tolerances, force limits predicted by the model cover all the forces measured for a specific pocket with excellent accuracy and consistency.

3.
Carbohydr Polym ; 271: 118405, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364549

RESUMO

In this study, cellulose nanocrystals (CNCs) with PEG grafts of various lengths (1 k, 2 k, 5 k, and 10 kDa) were prepared via a polydopamine (PDA) mediated method in the aqueous solution. The prepared CNC-PEGs were further used to reinforce the polyvinyl alcohol (PVA) at the loading of 0, 1, 3, 5, and 7 wt% in order to demonstrate the effects of the PEG length on the properties of the PVA/CNC nanocomposites. PEG surface modification resulted in simultaneous improvements in stiffness and toughness. The graft lengths have noticeable impacts on the properties of composites. The shorter graft yields better enhancement in strength and stiffness, attributable to the high efficiency in the stress transfer and high interface adhesion. The longer PEG graft length yields high graft-matrix entanglement, forming a thicker rubbery coating layer that enhances the toughness of PVA/CNC composites.


Assuntos
Celulose/química , Membranas Artificiais , Nanocompostos/química , Nanopartículas/química , Polietilenoglicóis/química , Módulo de Elasticidade , Indóis/química , Estrutura Molecular , Polímeros/química , Álcool de Polivinil/química , Resistência à Tração
4.
ACS Appl Mater Interfaces ; 13(34): 40731-40741, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34424665

RESUMO

Facile electron transport and intimate electronic contact at the catalyst-electrode interface are critical for the ideal performance of electrochemical devices such as glucose biofuel cells and biosensors. Here, through a comprehensive experimental-theoretical exploration, we demonstrate that engineering of interfacial properties, including interfacial electron dynamics, electron affinity, electrode-catalyst-adsorbate electrical synergy, and electrocatalytically active surface area, can lead to highly efficient graphene-based electrochemical devices. We selected two closely related but electronically and surface chemically different functionalized graphene analogues-graphene acid (GA) and reduced graphene oxide (rGO)-as the model graphenic platforms. Our studies reveal that compared to rGO, GA is a superior bifunctional catalyst with high oxygen reduction reaction (an onset potential of 0.8 V) and good glucose oxidation activities. Spectroscopic and electrochemical analysis of GA and rGO indicated that the higher carboxylic acid content on GA increases its overall electron affinity and coupled with improved conductivity and band alignment, which leads to GA's better electrochemical performance. The formulation of a heterostructure between GA and samarium oxide (Sm2O3) nanoparticles led to augmented conductivity (lower charge-transfer resistance) and glucose binding affinity, resulting in a further enhanced glucose oxidation activity. The interdimensional Sm2O3/GA heterostructure, leveraging their enhanced glucose oxidation capacity, exhibited excellent nonenzymatic amperometric glucose sensing performance, with a detection limit of 107 nM and a sensitivity of 20.8 µA/µM. Further, a nonenzymatic, membrane-free glucose biofuel cell (with Sm2O3/GA heterostructure as anode and GA as biocathode) produced a power density of 3.2 µW·cm-2 (in PBS spiked with 3 mM glucose), which can function as self-powered glucose sensors with 70 nM limit of detection. The study establishes the potential of interfacial engineering of GA to engage it as a highly tunable substrate for a broad range of electrochemical applications, especially in future self-powered biosensors.


Assuntos
Técnicas Biossensoriais/métodos , Glucose/análise , Grafite/química , Adsorção , Fontes de Energia Bioelétrica , Técnicas Biossensoriais/instrumentação , Catálise , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Glucose/química , Limite de Detecção , Nanopartículas Metálicas/química , Oxirredução , Óxidos/química , Samário/química , Eletricidade Estática
5.
Sci Total Environ ; 752: 141674, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889261

RESUMO

Over the past few decades, rigorous efforts have been undertaken to develop novel thermoelectrics (TEs) with high conversion efficiencies. However, poor TE device efficiencies and use of scarce and toxic constituent elements in major TEs raises valid questions about their ecological effectiveness. We evaluate this efficacy by investigating environmental performance of seven TE modules, spanning five different TEs, on a diverse range of impacts (including toxicity and scarcity) over their life cycle (cradle-to-grave). Exhaustive inventory is developed for all modules, particularly their production and end-of-life stages, in the first-ever exercise of its kind till date, to assess their benefits for applications involving constant waste heat emission. Three end-of-life scenarios are considered to determine ecological benefits and pitfalls of recycling TEs, a first in LCA literature on thermoelectrics. The results show the dominance of specific constituent elements and large processing-related electricity consumption on impacts caused by production for all modules. Over their life cycle, TE modules are seen to exhibit large positive environmental benefits, barring some exceptions, highlighting their substantial eco-credentials independent of the TE used. Also, barring circular economy approach in some cases, no end-of-life treatment is observed to significantly influence modular environmental impacts. Subsequent calculations show ecological benefits from TEs to be comparable with those from commonly used renewables like solar and wind energy, with the findings repeated under scenario-based sensitivity analysis despite 50% reduction in conversion efficiency and 15% lowering in usage duration, further validating their ecofriendly potential. Simultaneously, two key challenges that hinder large-scale application of TEs - marginal ecological benefits (even on converting high fraction of waste heat to electricity) and high costs - are pointed out. This work concludes by highlighting the urgent need for addressing major negative contributors to production-related impacts of this platform to boost its prospects for commercial application and transform its ecofriendly potential into reality.

6.
J Am Chem Soc ; 142(42): 17923-17927, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33030340

RESUMO

Fullerene-based low-dimensional (LD) heterostructures have emerged as excellent energy conversion materials. We constructed van der Waals 1T-MoS2/C60 0D-2D heterostructures via a one-pot synthetic approach for catalytic hydrogen generation. The interfacial 1T-MoS2-C60 and C60-C60 interactions as well as their electrocatalytic properties were finely controlled by varying the weight percentages of the fullerenes. 1T-MoS2 platforms provided a novel template for the formation of C60 nanosheets (NSs) within a very narrow fullerene concentration range. The heterostructure domains of 1T-MoS2 and C60 NSs exhibited excellent hydrogen evolution reaction (HER) performances, with one of the lowest onset potentials and ΔGH* values for LD non-precious nanomaterials reported to date.

7.
Sci Total Environ ; 720: 137634, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32146408

RESUMO

Microplastics (MPs) have been recognized as transport vectors for micropollutants in the natural water environment and the food web; therefore, the sorption behavior of contaminant on MPs has recently gained an increased attention. However, a consensus has not yet been reached and information about the adsorption of water contaminants on real MPs remains elusive. Herein, we raise the question of "Should we continue using pure polymers as surrogates for real MPs?" This first systematic study compared the adsorption of multiple micropollutants (i.e. a pesticide, a pharmaceutical, and perfluoroalkyl substances (PFAS)) on a large set of MPs (i.e. 20 well-characterized MPs) and kaolin. Material characterizations results showed various physicochemical and compositional differences between real and pure MPs. Pure polymers had lower normalized uptake values than real MPs in most cases. This was attributed to the surface roughness and/or the presence of fillers (e.g. talc and glass fiber) in real samples. Further, preloaded MPs with natural organic matter (NOM) showed an increased uptake of micropollutants due to forming a complex with NOM and/or co-sorption. These findings indicate that employing real MPs in research studies is critical for obtaining environmentally meaningful results, and the evaluation of MPs sorption behavior without NOM preloading can result in a significant underestimation for their actual values. We also provided an outlook the key areas for further investigations.

8.
Sci Rep ; 9(1): 8987, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222144

RESUMO

Epoxidation of high-linolenic perilla oil was carried out in the presence of solid acidic ion-exchange resin at varying reaction temperatures for 8 h. A pseudo two-phase kinetic model that captures the differences in reactivity of double bonds at various positions in the fatty acid of a triglyceride molecule during both epoxy formation and cleavage was developed. The proposed model is based on the Langmuir-Hinshelwood-Hougen-Watson (L-H-H-W) postulates and considers the adsorption of formic acid on the catalyst as the rate-determining step. To estimate the kinetic rate constants of various reactions, genetic algorithm was used to fit experimentally obtained iodine and epoxy values of epoxidized perilla oil. A re-parametrized form of Arrhenius equation was used in the proposed model to facilitate the precise estimation of parameters with least computational effort. The obtainment of the least error between experimentally determined and theoretically predicted iodine and epoxy values indicates the robustness of the proposed model.

9.
Carbohydr Polym ; 205: 27-34, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446104

RESUMO

Reactive extrusion was used for dicumyl peroxide (DCP)-initiated grafting of glycidyl methacrylate (GMA) to poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). The effects of GMA and DCP content and their weight ratio on the GMA grafting percentage (GP%), the polymer melt viscosity, and the PHBV molecular weight were investigated. FTIR spectroscopy determined that the DCP did indeed initiate GMA grafting. However, the changes in both the zero-shear viscosity (η0) and the molecular weight suggested the existence of crosslinking products in the extruded polymers. A negative correlation between the degree of crystallinity (χc) of the PHBV-g-GMA and the GP% suggested the influence of chain branching on crystallinity. In addition, the GMA content was found as a key factor determining the GP%. The PHBV-g-GMA was used as a matrix polymer in cellulose nanocomposites to evaluate its effects on CNC dispersion and CNC-matrix adhesion relative to the unmodified PHBV matrix. The SEM images and the change in crystallization temperature suggested enhanced dispersion of CNC in a PHBV-g-GMA matrix. However, little increase in strength properties were found with CNC addition suggesting inadequate stress transfer between the matrix and CNCs.

10.
ACS Omega ; 4(26): 21799-21808, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31891057

RESUMO

Photocure kinetics of acrylated epoxidized soybean oil (AESO) was studied via photocalorimetry without adding any diluent/comonomer, in the presence of two different photoinitiators, namely, 2,2-dimethoxy phenylacetophenone and 1-hydroxycyclohexyl phenyl ketone. The effect of varying photoinitiator concentration, light intensity, and temperature on the extent of crosslinking was calculated from the ratio of experimentally measured reaction enthalpy to the theoretical enthalpy of reaction (ΔH theoretical). Photocuring of AESO was observed to be a second-order reaction exhibiting autocatalytic behavior. Nevertheless, due to the occurrence of vitrification, incomplete crosslinking (α ≠ 1) was observed in most curing conditions. Rate constants and activation energies were determined using both nonlinear model-fitting and model-free isoconversional methods. Activation energy, as determined from the model-free isoconversional method, was observed to increase as the reaction proceeded, indicating the shift in cure mechanism from kinetic-controlled to diffusion-controlled. Finally, the reaction termination mechanism was observed to be a combination of second-order and primary radical termination mechanisms.

11.
ACS Appl Mater Interfaces ; 10(3): 2236-2241, 2018 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-29309124

RESUMO

We demonstrate the potential of polymer-derived ceramics (PDC) as next-generation sustainable thermoelectrics. Thermoelectric behavior of polymer-derived silicon oxycarbide (SiOC) ceramics (containing hexagonal boron nitride (h-BN) as filler) was studied as a function of measurement temperature. SiOC, sintered at 1300 °C exhibited invariant low thermal conductivity (∼1.5 W/(m·K)) over 30-600 °C, coupled with a small increase in both Seebeck coefficient and electrical conductivity, with increase in measurement temperature (30-150 °C). SiOC ceramics containing 1 wt % h-BN showed the highest Seebeck coefficient (-33 µV/K) for any PDC thus far.

12.
ACS Omega ; 3(10): 14361-14370, 2018 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31458124

RESUMO

The presence of highly modifiable chemical functional groups, abundance of functional groups, and their biological origin make proteins an important class of biomaterials from a fundamental science and applied engineering perspective. Hence, the utilization of proteins from the animal rendering industry (animal protein, AP) for high-value, nonfeed, and nonfertilizer applications is intensely pursued. Although this leads to the exploration of protein-derived plastics as a plausible alternative, the proposed methods are energy-intensive and not based on protein in its native form, which leads to high processing and production costs. Here, we propose, for the first time, novel pathways to develop engineered hybrid systems utilizing AP in its native form and epoxy resins with mechanical properties ranging from toughened thermosets to elastic epoxy-based systems. Furthermore, we demonstrate the capability to engineer the properties of epoxy-AP hybrids from high-strength hybrids to elastic films through controlling the interaction, hydrophilicity, as well as the extent of cross-linking and network density. Through the facile introduction of cochemicals, a sevenfold increase in the mechanical properties of the conventional epoxy-AP hybrid is achieved. Similarly, because of better compatibility afforded by the similar hydrophilicity, AP demonstrated higher cross-linking capability with a water-soluble epoxy (WEP) matrix, resulting in an elastic WEP-AP hybrid without any external aid.

13.
Sci Rep ; 7(1): 11086, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28894228

RESUMO

The aim of this work was to enhance the transportation of the galantamine to the brain via ascorbic acid grafted PLGA-b-PEG nanoparticles (NPs) using SVCT2 transporters of choroid plexus. PLGA-b-PEG copolymer was synthesized and characterized by 1H NMR, gel permeation chromatography, and differential scanning calorimetry. PLGA-b-PEG-NH2 and PLGA-b-mPEG NPs were prepared by nanoprecipitation method. PLGA-b-PEG NPs with desirable size, polydispersity, and drug loading were used for the conjugation with ascorbic acid (PLGA-b-PEG-Asc) to facilitate SVCT2 mediated transportation of the same into the brain. The surface functionalization of NPs with ascorbic acid significantly increased cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells as compared to plain PLGA and PLGA-b-mPEG NPs. In vivo pharmacodynamic efficacy was evaluated using Morris Water Maze Test, Radial Arm Maze Test and AChE activity in scopolamine induced amnetic rats. In vivo pharmacodynamic studies demonstrated significantly higher therapeutic and sustained action by drug loaded PLGA-b-PEG-Asc NPs than free drugs and drug loaded plain PLGA as well as PLGA-b-mPEG NPs. Additionally, PLGA-b-PEG-Asc NPs resulted in significantly higher biodistribution of the drug to the brain than other formulations. Hence, the results suggested that targeting of bioactives to the brain by ascorbic acid grafted PLGA-b-PEG NPs is a promising approach.


Assuntos
Ácido Ascórbico/química , Encéfalo/efeitos dos fármacos , Inibidores da Colinesterase/administração & dosagem , Portadores de Fármacos/química , Galantamina/administração & dosagem , Nanopartículas/química , Polímeros/química , Animais , Encéfalo/metabolismo , Linhagem Celular , Inibidores da Colinesterase/farmacocinética , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Ativação Enzimática/efeitos dos fármacos , Galantamina/farmacocinética , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Poliglactina 910/química , Ratos , Distribuição Tecidual
14.
Polymers (Basel) ; 9(1)2017 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970698

RESUMO

Bio-based polymer foams have been gaining immense attention in recent years due to their positive contribution towards reducing the global carbon footprint, lightweighting, and enhancing sustainability. Currently, polylactic acid (PLA) remains the most abundant commercially consumed biopolymer, but suffers from major drawbacks such as slow crystallization rate and poor melt processability. However, blending of PLA with a secondary polymer would enhance the crystallization rate and the thermal properties based on their compatibility. This study investigates the physical and compatibilized blends of PLA/poly (butylene succinate-co-adipate) (PBSA) processed via supercritical fluid-assisted (ScF) injection molding technology using nitrogen (N2) as a facile physical blowing agent. Furthermore, this study aims at understanding the effect of blending and ScF foaming of PLA/PBSA on crystallinity, melting, and viscoelastic behavior. Results show that compatibilization, upon addition of triphenyl phosphite (TPP), led to an increase in molecular weight and a shift in melting temperature. Additionally, the glass transition temperature (Tg) obtained from the tanδ curve was observed to be in agreement with the Tg value predicted by the Gordon⁻Taylor equation, further confirming the compatibility of PLA and PBSA. The compatibilization of ScF-foamed PLA⁻PBSA was found to have an increased crystallinity and storage modulus compared to their physically foamed counterparts.

15.
Carbohydr Polym ; 157: 1333-1340, 2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-27987840

RESUMO

Dialdehyde carboxymethyl cellulose (DCMC) crosslinked soy protein isolate (SPI) films were prepared by solvent casting method. Effect of DCMC treatment on mechanical properties, water sensitivity, light barrier properties and thermal stability were investigated. Significant increase in tensile strength (TS) was observed (up to 218%), suggesting occurrence of highly effective crosslinking between SPI and DCMC. Significant improvement in TS compared to other dialdehyde polysaccharide crosslinking agents such as dialdehyde starch is likely due to higher compatibility of DCMC with SPI, as was further confirmed by SEM images. Crosslinking also led to reduction in water vapor permeability and moisture content along with an increase of insoluble mass percentage, indicating improvement in water resistance of these bio-based protein films. Thermal stability of protein films also showed improvement post crosslinking of DCMC.


Assuntos
Carboximetilcelulose Sódica/química , Proteínas de Soja/química , Permeabilidade , Vapor , Resistência à Tração , Água/química
16.
Colloids Surf B Biointerfaces ; 126: 590-597, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25591850

RESUMO

Polyamidoamine (PAMAM) dendrimer was conjugated with both carboxymethyl-ß-cyclodextrin (ßCD) and poly(ethylene glycol) (PEG). Cyclic RGD peptide, used as a tumor targeting ligand, was then selectively conjugated onto the distal ends of the PEG arms. The resulting ßCD-PAMAM-PEG-cRGD polymer was able to form stable and uniform nanoparticles (NPs) in aqueous solution. Doxorubicin (Dox), a model hydrophobic anticancer drug, was effectively encapsulated in the NPs via an inclusion complex formed between the drug and ßCD. The Dox loading level was 16.8 wt%. The cellular uptake of cRGD-conjugated Dox-loaded NPs in the U87MG cell line was much higher than that of non-targeted NPs. Furthermore, the anti-proliferative effect of the cRGD-conjugated NPs was superior to that of free drug and non-targeted NPs. These results suggest that NPs formed by ßCD-PAMAM-PEG-cRGD with a high drug payload may significantly improve the anticancer efficacy by tumor-targeted delivery and enhanced cellular uptake.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Portadores de Fármacos/síntese química , Nanoestruturas/química , Peptídeos Cíclicos/química , Poliaminas/química , Polietilenoglicóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , beta-Ciclodextrinas/química
17.
PLoS One ; 9(2): e89227, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24586612

RESUMO

Open vascular reconstructions frequently fail due to the development of recurrent disease or intimal hyperplasia (IH). This paper reports a novel drug delivery method using a rapamycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs)/pluronic gel system that can be applied periadventitially around the carotid artery immediately following the open surgery. In vitro studies revealed that rapamycin dispersed in pluronic gel was rapidly released over 3 days whereas release of rapamycin from rapamycin-loaded PLGA NPs embedded in pluronic gel was more gradual over 4 weeks. In cultured rat vascular smooth muscle cells (SMCs), rapamycin-loaded NPs produced durable (14 days versus 3 days for free rapamycin) inhibition of phosphorylation of S6 kinase (S6K1), a downstream target in the mTOR pathway. In a rat balloon injury model, periadventitial delivery of rapamycin-loaded NPs produced inhibition of phospho-S6K1 14 days after balloon injury. Immunostaining revealed that rapamycin-loaded NPs reduced SMC proliferation at both 14 and 28 days whereas rapamycin alone suppressed proliferation at day 14 only. Moreover, rapamycin-loaded NPs sustainably suppressed IH for at least 28 days following treatment, whereas rapamycin alone produced suppression on day 14 with rebound of IH by day 28. Since rapamycin, PLGA, and pluronic gel have all been approved by the FDA for other human therapies, this drug delivery method could potentially be translated into human use quickly to prevent failure of open vascular reconstructions.


Assuntos
Túnica Adventícia/efeitos dos fármacos , Artérias Carótidas/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Sirolimo/administração & dosagem , Túnica Adventícia/metabolismo , Túnica Adventícia/patologia , Animais , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Sobrevivência Celular/efeitos dos fármacos , Hiperplasia/metabolismo , Hiperplasia/patologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas/metabolismo
18.
Nanoscale ; 5(20): 9924-33, 2013 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-23986296

RESUMO

Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.


Assuntos
Antineoplásicos/toxicidade , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Micelas , Octreotida/toxicidade , Estilbenos/toxicidade , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Biomarcadores Tumorais/metabolismo , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Linhagem Celular Tumoral , Humanos , Nanomedicina , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/química , Poliésteres/química , Polietilenoglicóis/química , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/química
19.
Biomaterials ; 34(21): 5244-53, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23582862

RESUMO

In the absence of effective therapy for prostate cancer, there is an immense need for developing improved therapeutic options for the management of this disease. This study has demonstrated that aptamer-conjugated unimolecular micelles can improve the in vivo tumor biodistribution of systemically administered anti-cancer drugs in prostate cancer expressing prostate-specific membrane antigen (PSMA). The aptamer-conjugated unimolecular micelles were formed by individual hyperbranched polymer molecules consisting of a hyperbranched H40 polymer core and approximately 25 amphiphilic polylactide-poly(ethlyene glycol) (PLA-PEG) block copolymer arms (H40-PLA-PEG-Apt). The unimolecular micelles with an average hydrodynamic diameter of 69 nm exhibited a pH-sensitive and controlled drug release behavior. The targeted unimolecular micelles (i.e., DOX-loaded H40-PLA-PEG-Apt) exhibited a much higher cellular uptake in PSMA positive CWR22Rν1 prostate carcinoma cells than non-targeted unimolecular micelles (i.e., DOX-loaded H40-PLA-PEG), thereby leading to a significantly higher cytotoxicity. The DOX-loaded unimolecular micelles up-regulated the cleavage of PARP and Caspase 3 proteins and increased the protein expression of Bax along with a concomitant decrease in Bcl2. These micelles also increased the protein expression of cell cycle regulation marker P21 and P27. In CWR22Rν1 tumor-bearing mice, DOX-loaded H40-PLA-PEG-Apt micelles (i.e., targeted) also exhibited a much higher level of DOX accumulation in the tumor tissue than DOX-loaded H40-PLA-PEG micelles (i.e., non-targeted). These findings suggest that aptamer-conjugated unimolecular micelles may potentially be an effective drug nanocarrier to effectively treat prostate cancer.


Assuntos
Aptâmeros de Nucleotídeos/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Micelas , Neoplasias da Próstata/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Portadores de Fármacos/síntese química , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Nus , Peso Molecular , Tamanho da Partícula , Poliésteres/síntese química , Poliésteres/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Neoplasias da Próstata/patologia , Distribuição Tecidual/efeitos dos fármacos
20.
Mater Sci Eng C Mater Biol Appl ; 32(6): 1674-81, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24364976

RESUMO

In this study, poly(ε-caprolactone) (PCL)/sodium chloride (NaCl), PCL/poly(ethylene oxide) (PEO)/NaCl and PCL/PEO/NaCl/hydroxyapatite (HA) composites were injection molded and characterized. The water soluble and sacrificial polymer, PEO, and NaCl particulates in the composites were leached by deionized water to produce porous and interconnected microstructures. The effect of leaching time on porosity, and residual contents of NaCl and NaCl/HA, as well as the effect of HA addition on mechanical properties was investigated. In addition, the biocompatibility was observed via seeding human mesenchymal stem cells (hMSCs) on PCL and PCL/HA scaffolds. The results showed that the leaching time depends on the spatial distribution of sacrificial PEO phase and NaCl particulates. The addition of HA has significantly improved the elastic (E') and loss moduli (E″) of PCL/HA scaffolds. Human MSCs were observed to have attached and proliferated on both PCL and PCL/HA scaffolds. Taken together, the molded PCL and PCL/HA scaffolds could be good candidates as tissue engineering scaffolds. Additionally, injection molding would be a potential and high throughput technology to fabricate tissue scaffolds.


Assuntos
Materiais Biocompatíveis/química , Durapatita/química , Poliésteres/química , Alicerces Teciduais/química , Células Cultivadas , Humanos , Teste de Materiais/métodos , Células-Tronco Mesenquimais/química , Polietilenoglicóis/química , Polímeros/química , Porosidade , Cloreto de Sódio/química , Engenharia Tecidual/métodos , Água/química
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