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The rise of antibiotic resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), requires novel approaches to combat infections. Medical devices like implants and wound dressings are frequently used in conjunction with antibiotics, motivating the development of antibacterial biomaterials capable of exhibiting combined antibacterial effects with conventional antibiotics. This study explores the synergistic antibacterial effects of combining antimicrobial peptide (AMP) functionalized hydrogel particles with conventional antibiotics, vancomycin (VCM) and oxacillin (OXA), against Staphylococcus aureus and MRSA. The AMP employed, RRPRPRPRPWWWW-NH2, has previously demonstrated broad-spectrum activity and enhanced stability when attached to hydrogel substrates. Here, checkerboard assays revealed additive and synergistic interactions between the free AMP and both VCM and OXA against Staphylococcus aureus and MRSA. Notably, the AMP-OXA combination displayed a significant synergistic effect against MRSA, with a 512-fold reduction in OXA's minimum inhibitory concentration (MIC) when combined with free AMP. The observed synergism against MRSA was retained upon covalent AMP immobilization onto the hydrogel particles; however, at a lower rate with a 64-fold reduction in OXA MIC. Despite this, the OXA-AMP hydrogel particle combinations retained considerable synergistic potential against MRSA, a strain resistant to OXA, highlighting the potential of AMP-functionalized materials for enhancing antibiotic efficacy. These findings underscore the importance of developing antimicrobial biomaterials for future medical devices to fight biomaterial-associated infections and reverse antimicrobial resistance.
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There is a strong need to develop an insulin delivery system suitable for oral administration and preserving natural (α-helix) insulin conformation. In this work, we fabricated alginate-gelatin hydrogel beads for insulin encapsulation. Altering matrix composition and crosslinking agents has resulted in various surface morphologies and internal spatial organization. The structures of the insulin-loaded matrices were studied using optical and field emission electronic microscopy. We use FTIR spectroscopy to identify insulin conformation changes as affected by the hydrogel matrices. It was found that blended alginate-gelatin matrices demonstrate better encapsulation efficiency and stronger swelling resistance to a simulated gastric environment than sodium alginate beads crosslinked with the CaCl2. FTIR measurements reveal conformation changes in insulin. It is also confirmed that in the presence of gelatin, the process of insulin fibrinogenesis ceases due to intermolecular interaction with the gelatin. Performed molecular modeling shows that dipole-dipole interactions are the dominating mechanism that determines insulin behavior within the fabricated matrix.
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Hidrogéis , Insulina , Hidrogéis/química , Gelatina/química , Alginatos/químicaRESUMO
Amylase is an enzyme used to hydrolyze starch in order to obtain different products that are mainly used in the food industry. The results reported in this article refer to the immobilization of α-amylase in gellan hydrogel particles ionically cross-linked with Mg2+ ions. The obtained hydrogel particles were characterized physicochemically and morphologically. Their enzymatic activity was tested using starch as a substrate in several hydrolytic cycles. The results showed that the properties of the particles are influenced by the degree of cross-linking and the amount of immobilized α-amylase enzyme. The temperature and pH at which the immobilized enzyme activity is maximum were T = 60 °C and pH = 5.6. The enzymatic activity and affinity of the enzyme to the substrate depend on the particle type, and this decreases for particles with a higher cross-linking degree owing to the slow diffusion of the enzyme molecules inside the polymer's network. By immobilization, α-amylase is protected from environmental factors, and the obtained particles can be quickly recovered from the hydrolysis medium, thus being able to be reused in repeated hydrolytic cycles (at least 11 cycles) without a substantial decrease in enzymatic activity. Moreover, α-amylase immobilized in gellan particles can be reactivated via treatment with a more acidic medium.
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Hidrogéis , alfa-Amilases Pancreáticas , Suínos , Estabilidade Enzimática , Enzimas Imobilizadas/química , alfa-Amilases/metabolismo , Temperatura , Íons , Amido , Concentração de Íons de Hidrogênio , AnimaisRESUMO
Subcutaneous (SC) administration is a desired route for monoclonal antibodies (mAbs). However, formulating mAbs for small injection volumes at high concentrations with suitable stability and injectability is a significant challenge. Here, this work presents a platform technology that combines the stability of crystalline antibodies with injectability and tunability of soft hydrogel particles. Composite alginate hydrogel particles are generated via a gentle centrifugal encapsulation process which avoids use of chemical reactions or an external organic phase. Crystalline suspension of anti-programmed cell death protein 1 (PD-1) antibody (pembrolizumab) is utilized as a model therapeutic antibody. Crystalline forms of the mAb encapsuled in the hydrogel particles lead to stable, high concentration, and injectable formulations. Formulation concentrations as high as 315 mg mL-1 antibody are achieved with encapsulation efficiencies in the range of 89-97%, with no perceivable increase in the number of antibody aggregates. Bioanalytical studies confirm superior maintained quality of the antibody in comparison with formulation approaches involving organic phases and chemical reactions. This work illustrates tuning the alginate particles' disintegration by using partially oxide alginates. Crystalline mAb-laden particles are evaluated for their biocompatibility using cell-based in vitro assays. Furthermore, the pharmacokinetics (PK) of the subcutaneously delivered human anti-PD-1 mAb in crystalline antibody-laden alginate hydrogel particles in Wistar rats is evaluated.
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Alginatos , Anticorpos Monoclonais , Ratos , Animais , Humanos , Alginatos/química , Ratos Wistar , Anticorpos Monoclonais/farmacocinética , Tela Subcutânea/metabolismo , Hidrogéis/químicaRESUMO
Poly(ethylene glycol) diacrylate (PEGDA) microgels with tuneable size and porosity find applications as extracellular matrix mimics for tissue-engineering scaffolds, biosensors, and drug carriers. Monodispersed PEGDA microgels were produced by modular droplet microfluidics using the dispersed phase with 49-99 wt% PEGDA, 1 wt% Darocur 2959, and 0-50 wt% water, while the continuous phase was 3.5 wt% silicone-based surfactant dissolved in silicone oil. Pure PEGDA droplets were fully cured within 60 s at the UV light intensity of 75 mW/cm2. The droplets with higher water content required more time for curing. Due to oxygen inhibition, the polymerisation started in the droplet centre and advanced towards the edge, leading to a temporary solid core/liquid shell morphology, confirmed by tracking the Brownian motion of fluorescent latex nanoparticles within a droplet. A volumetric shrinkage during polymerisation was 1-4% for pure PEGDA droplets and 20-32% for the droplets containing 10-40 wt% water. The particle volume increased by 36-50% after swelling in deionised water. The surface smoothness and sphericity of the particles decreased with increasing water content in the dispersed phase. The porosity of swollen particles was controlled from 29.7% to 41.6% by changing the water content in the dispersed phase from 10 wt% to 40 wt%.
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Hidrogéis , Microgéis , Dispositivos Lab-On-A-Chip , Microfluídica , Microesferas , Polietilenoglicóis , ÁguaRESUMO
Heavy metal ions (HMI) have attracted worldwide concern due to their serious environmental pollution which led to the risk of health conditions. From Red Malus floribunda fruits, nitrogen-doped carbon dots (N-CDs) were prepared, followed by hybrid-spherical shaped hydrogel particles (CGCDs) were prepared. The prepared CGCDs were utilized as adsorbents for HMI-(Hg(II), Cd(II), Pb(II), and Cr(III)) from water. N-CDs with about 4.0 nm in diameter were characterized by various techniques such as field emission-scanning electron microscopy (FE-SEM) and attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR) that confirm the presence of nitrogen, oxygen, and carbon functionalities. The prepared spherical CGCDs were characterized very well before it was used as HMI adsorbents. The sizes of the CGCDs were ranges between 20 and 300 µm and the degree of swelling was calculated as 1320 %. ATR-FTIR and X-ray diffraction analyses reveal the presence of N-CDs in CGCDs. Further, FE-SEM confirms the spherical shape morphology of CGCDs. Three different concentrations of HMI solutions were 500 mg/L, 1000 mg/L, and 1500 mg/L. Hg(II) adsorbed proficiently by CGCDs in single metal ion systems with ~72 % and almost complete removal of Hg(II) ions (99 %) in multiple metal ion systems was observed. Moreover, all metal ions Hg(II), Cd(II), Pb(II), and Cr(III) were efficiently (>70 %) removed in multiple systems by CGCDs. After HMI adsorption experiments, the elemental mapping from FE-SEM and X-ray photoelectron spectroscopy studies conveys the presence of HMI on CGCDs. This suggests that CGCDs would be a suitable adsorbent for the simultaneous removal of multiple HMI from wastewater.
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Metais Pesados , Poluentes Químicos da Água , Adsorção , Carbono , Hidrogéis , Íons , Metais Pesados/análise , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Fluorescence probes have widely been used for detecting and imaging Ca2+-enriched parts of cells but more rarely for quantitative determination of concentrations. In this study we show how this can be achieved by a novel approach using hydrogel particles. In a microfluidic co-flow arrangement spherical droplets were generated from an aqueous solution of acrylamide, N,N'-methylenebisacrylamide crosslinker and photoinitiator and subsequently photo-cured in situ yielding gel particles in a sub millimeter range. These particles were separated, dried under reduced pressure and re-swollen in water containing Rhod-5N tri potassium salt as calcium ion selective fluorescence probe. After that the particles were dried again and stored for further investigations. Upon exposure of dried particles to calcium chloride solutions they swell and take up Ca2+-ions forming a strong fluorescing complex with Rhod-5N. Thus, fluorescence intensity increases with calcium ion concentration. Up to ca. 0.50 mM the enhancement effect is strong and then becomes considerably weaker. The intensity-concentration-dependence is well described by an equation derived from the equilibrium of the formation of a 1:1 Ca2+:Rhod-5N complex. The particles allow for a fast optical determination of Ca2+-concentrations up to 0.50 mM in analyte volumes down to below 10 µL.
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Oral drug products have become indispensable in modern medicine because of their exceptional patient compliance. However, poor bioavailability of ubiquitous low-water-soluble active pharmaceutical ingredients (APIs) and lack of efficient oral drug formulations remain as significant challenges. Nanocrystalline formulations are an attractive route to increase API solubility, but typically require abrasive mechanical milling and several processing steps to create an oral dosage form. Using the dual amphiphilic and thermoresponsive properties of methylcellulose (MC), a new thermogelling nanoemulsion and a facile thermal dripping method are developed for efficient formulation of composite particles with the MC matrix embedded with precisely controlled API nanocrystals. Moreover, a fast and tunable release performance is achieved with the combination of a fast-eroding MC matrix and fast-dissolving API nanocrystals. Using the versatile thermal processing approach, the thermogelling nanoemulsion is easily formulated into a wide variety of dosage forms (nanoparticle suspension, drug tablet, and oral thin film) in a manner that avoids nanomilling. Overall, the proposed thermogelling nanoemulsion platform not only broadens the applications of thermoresponsive nanoemulsions but also shows great promise for more efficient formulation of oral drug products with high quality and tunable fast release.
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Metilcelulose , Química Farmacêutica , Nanopartículas , SolubilidadeRESUMO
In the present study, the effect of transglutaminase (TGase) concentration on the physical and oxidative stabilities of filled hydrogel particles created by biopolymer phase separation was investigated. The results showed that filled hydrogels had relatively smaller particle sizes, higher absolute zeta-potentials, higher interfacial layer thicknesses and lightness values with the increasing of TGase concentration (P < 0.05), as evidenced by the apparent viscosity and viscoelasticity behavior. However, the relatively higher TGase concentration promoted the protein aggregation, which weakens the protection of the surface protein layer, having the negatively impacted the physical stability of filled hydrogels. Microstructural images which obtained via cryo-scanning electron microscopy also verified the above results. In particular, it is noted that filled hydrogels displayed the lowest degrees of lipid and protein oxidation during 10 days of storage (P < 0.05) at TGase concentration of 10 U/g. Prevention against oxidation was attributed mainly to TGase crosslinking of protein molecules on the surface of droplets, which likely provided a denser interface around lipid droplets. Our results indicated that TGase was a favourable agent to crosslink protein on the surface of lipid and improve the physical and oxidative stability of filled hydrogel particles.
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Hidrogéis/química , Gotículas Lipídicas/química , Pectinas/química , Transglutaminases/química , Proteínas do Soro do Leite/química , Portadores de Fármacos , Estabilidade de Medicamentos , Elasticidade , Humanos , Concentração de Íons de Hidrogênio , Oxirredução , Tamanho da Partícula , Reologia , Soluções , ViscosidadeRESUMO
The impact of secondary polysaccharide, i.e., low methoxyl pectin (LMP) or κ-carrageenan (KC), and its concentration (0.2, 0.4, and 0.6%) on particle size, shape, morphological, textural properties and swelling behavior of sodium alginate (ALG)- based double-network hydrogel particles, as well as the viability of encapsulated probiotics Lactobacillus rhamnosus GG (LGG) in simulated sequential gastrointestinal (GI) digestion was investigated. We found the addition of LMP impaired the sphericity of double-network hydrogel particles, while the incorporation of KC increased the particle size. The FT-IR results indicated the miscibility and cross-linking capacity of the two polysaccharides in forming double-network hydrogel particles. With respect to the swelling behavior in simulated GI digestion, all hydrogel particles shrank in simulated gastric fluid (SGF) but swelled in simulated intestinal fluid (SIF). Among the two types of double-networking, ALG-KC hydrogel particles showed noticeable shrank in SGF in conjunction with the reduced swelling in SIF, which was unfavorable for protection and the controlled release of probiotics. In the case of death rate of encapsulated LGG, the presence of LMP at a lower level (0.2 or 0.4%) exhibited protective effect against LGG death during the sequential GI digestion, while addition of KC demonstrated an opposite role.
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Alginatos/farmacologia , Biopolímeros/farmacologia , Digestão/efeitos dos fármacos , Trato Gastrointestinal/fisiologia , Hidrogéis/farmacologia , Probióticos/farmacologia , Liofilização , Trato Gastrointestinal/efeitos dos fármacos , Lacticaseibacillus rhamnosus/ultraestrutura , Viabilidade Microbiana/efeitos dos fármacos , Tamanho da Partícula , Reologia , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , ViscosidadeRESUMO
We describe here experiments on the mechanics of hydrogel particle packings from the Behringer lab, performed between 2012 and 2015. These experiments quantify the evolution of all contact forces inside soft particle packings exposed to compression, shear, and the intrusion of a large intruder. The experimental set-ups and processes are presented and the data are concomitantly published in a repository (Barés et al. in Dryad, Dataset 10.5061/dryad.6djh9w0x8, 2019).
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Filled hydrogel particles can be fabricated by incorporating an oil-in-water emulsion into portions of separated incompatible lower and upper phases together and remixing with later acidification to pH 5.0. The purpose of present study was to investigate the influence of different heat-denatured whey protein concentrates (HWPC)/high methoxy pectin (HMP) mass ratios (1:1, 2:1, 3:1, 4:1, and 5:1) of phase separated systems on the physical characteristics and stabilities of filled hydrogel particles. The results showed that the particle size of filled hydrogel particles significantly decreased with increasing HWPC/HMP mass ratios (Pâ¯<â¯0.05), which was verified by reduced interfacial layer thickness. Moreover, decreased particle size also induced consistent reduction of the apparent viscosity and slightly increased the lightness. In particular, when the HWPC/HMP mass ratio was 3:1, the filled hydrogel particles exhibited the lowest amount of conjugated dienes and thiobarbituric acid-reactive substances after 10â¯days of storage (Pâ¯<â¯0.05), which was mainly due to the highest amount of biopolymers distributed at the interfacial membrances (Pâ¯<â¯0.05). Our results indicate that the phase separation system formed by HWPC/HMP mass ratio of 3:1 could be used to fabricate filled hydrogel particles with amplified stabilities at acidic pH for novel delivery systems.
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Emulsões/química , Hidrogéis/química , Pectinas/química , Proteínas do Soro do Leite/química , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Transição de Fase , Propriedades de Superfície , Tiobarbitúricos/química , Temperatura de Transição , ViscosidadeRESUMO
Currently, the method of external ionic gelation for the preparation of alginate particles is successfully used not only in the field of pharmacy and medicine, but also especially in the field of biotechnology. Therefore, the preparation of alginate particles and their subsequent evaluation using principal component analysis was the key task of our experiment. To optimize this method, we focused on the evaluation of the effect of formulation (the polymer concentration, the hardening solution concentration) and process parameters (the outer diameter of the injection needle) on the properties of the resulting beads (yield, sphericity factor, equivalent diameter and swelling capacity at pH 6). Using multivariate data analysis, the major influence on the resulting properties of the prepared particles was confirmed only in sodium alginate concentration. Obtained results verified the reliable and safe potential of the external ionic gelation for preparation alginate-based particulate dosage forms.
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Alginatos/química , Cobre/química , Polímeros , Análise de Componente PrincipalRESUMO
We report a tungsten disulfide (WS2) nanosheet-immobilized hydrogel system that can inhibit oxidative stress on living cells. First, we fabricated a highly stable suspension of WS2 nanosheets as a radical scavenger by enveloping them with the amphiphilic poly(ε-caprolactone)- b-poly(ethylene oxide) copolymer (PCL- b-PEO) during in situ liquid exfoliation in aqueous medium. After the PCL- b-PEO-enveloped WS2 nanosheets were embedded in three types of hydrogel systems, including carrageenan gum/locust bean gum bulk hydrogels, physically cross-linked alginate microparticles, and covalently cross-linked PEG hydrogel microparticles, they retained their characteristic optical properties. Intriguingly, the WS2 nanosheet-immobilized hydrogel particles exhibited sustainable radical scavenging performance without any deterioration in the original activity of the WS2 nanosheets, even after repeated use. This implies that the hydrogen atoms dissociated from the chalcogen of the WS2 nanosheets effectively scavenged free radicals through the hydrogel mesh. Because of this unique behavior, the coexistence of the WS2 nanosheets with living cells in the hydrogel matrix improved cell viability up to 40%, which demonstrates that the WS2 nanosheets can suppress oxidative stress on living cells.
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Materiais Biocompatíveis , Dissulfetos , Sequestradores de Radicais Livres , Hidrogéis , Estresse Oxidativo/efeitos dos fármacos , Tungstênio , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Dissulfetos/química , Dissulfetos/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Poliésteres/química , Poliésteres/farmacologia , Tungstênio/química , Tungstênio/farmacologiaRESUMO
Recently, in order to increase and improve treatment efficacy of hemoperfusion, research and development of novel adsorbents have been paid much attention. Herein, three-dimensional (3D) graphene oxide (GO) skeleton guided poly(acrylic acid) (PAA) composite hydrogel particles (HPs) used for hemoperfusion were prepared by a core-shell template method. The 3D GO skeletons with millimeter-scale were first constructed with the assistance of templates, dissolvable poly(ether sulfone) hollow particles, which were prepared by a phase inversion technique; then, PAA hydrogels were formed and distributed on the surface of the 3D GO skeleton. The obtained HPs showed a special hierarchical pore microstructure, small size, and uniform spherical shape. Compared with pure PAA hydrogels, the swelling ratios of the HPs were significantly restricted, and the porosities were remarkably increased; the compressive stress and the elongation at break were improved at the same time. The hemocompatibility tests, including protein adsorption, hemolysis ratio, complement and contact activation, platelet adhesion, and clotting time, were carried out, and the results indicated that the HPs showed good hemocompatibility. The adsorption results indicated that the HPs exhibited good removal efficiency toward exogenous and endogenous toxins. In general, the suitable physical and mechanical properties and the excellent hemocompatibility and adsorption capacities made the composite hydrogel particle a promising candidate for novel hemoperfusion adsorbents.
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The synthesis of materials that can mimic the mechanical, and ultimately functional, properties of biological cells can broadly impact the development of biomimetic materials, as well as engineered tissues and therapeutics. Yet, it is challenging to synthesize, for example, microparticles that share both the anisotropic shapes and the elastic properties of living cells. Here, a cell-directed route to replicate cellular structures into synthetic hydrogels such as polyethylene glycol (PEG) is described. First, the internal and external surfaces of chemically fixed cells are replicated in a conformal layer of silica using a sol-gel process. The template is subsequently removed to render shape-preserved, mesoporous silica replicas. Infiltration and cross-linking of PEG precursors and dissolution of the silica result in a soft hydrogel replica of the cellular template as demonstrated using erythrocytes, HeLa, and neuronal cultured cells. The elastic modulus can be tuned over an order of magnitude (≈10-100 kPa) though with a high degree of variability. Furthermore, synthesis without removing the biotemplate results in stimuli-responsive particles that swell/deswell in response to environmental cues. Overall, this work provides a foundation to develop soft particles with nearly limitless architectural complexity derived from dynamic biological templates.
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Materiais Biomiméticos/química , Forma Celular/fisiologia , Técnicas Citológicas/métodos , Hidrogéis/química , Biologia Sintética/métodos , Células Cultivadas , Módulo de Elasticidade/fisiologia , Células HeLa , Humanos , Dióxido de Silício/químicaRESUMO
Macroscopic hydrogels are commonly used as injectable scaffolds or fillers, however they may easily obstruct blood vessels, which poses risks and limits their clinical use. In the present study, three types of hyaluronic acid (HA)-based hydrogel micro-particles with non-covalent, covalent semi-interpenetrating and conventional 3D molecular networks, have been designed, fabricated and characterized. The micro-particles are spherical, biconcave or irregular in shape and their diameter ranged between 2.5 and 3.5⯵m; their suspensions exhibit a tuneable viscosity, shear-thinning behaviour, dynamic stability and dispersity in microfluidic flow as a result of their specific particulate nature, providing thus a well-controlled injectable platform. Hydrogel particle suspensions also demonstrate an enhanced safety profile, in terms of the dispersity, cell safety, and hemocompatibility. In addition, Rhodamine 6G has successfully been loaded and released from the particles as a model for drug delivery. Functionalisation of hydrogel microparticles using synthetic polymers has been proven to be a cost-effective way to achieve desirable rheological properties and flow dynamic stability with improved physicochemical properties and biocompatibility in vitro, showing promise as a multifunctional biomedical material for various advanced surgical devices and therapies.
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Portadores de Fármacos/química , Ácido Hialurônico/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Ácido Hialurônico/toxicidade , Hidrogéis , Dispositivos Lab-On-A-Chip , Microesferas , Tamanho da Partícula , Polietilenoglicóis/química , Povidona/química , Reologia , Rodaminas/administração & dosagem , Rodaminas/química , Rodaminas/farmacologia , Propriedades de Superfície , Trombose/induzido quimicamente , ViscosidadeRESUMO
Hydrogel particles are versatile materials that provide exquisite, tunable control over the sequestration and delivery of materials in pharmaceutics, tissue engineering, and photonics. The favorable properties of hydrogel particles depend largely on their size, and particles ranging from nanometers to micrometers are used in different applications. Previous studies have only successfully fabricated these particles in one specific size regime and required a variety of materials and fabrication methods. A simple yet powerful system is developed to easily tune the size of polypeptide-based, thermoresponsive hydrogel particles, from the nano- to microscale, using a single starting material. Particle size is controlled by the self-assembly and unique phase transition behavior of elastin-like polypeptides in bulk and within microfluidic-generated droplets. These particles are then stabilized through ultraviolet irradiation of a photo-crosslinkable unnatural amino acid (UAA) cotranslationally incorporated into the parent polypeptide. The thermoresponsive property of these particles provides an active mechanism for actuation and a dynamic responsive to the environment. This work represents a fundamental advance in the generation of crosslinked biomaterials, especially in the form of soft matter colloids, and is one of the first demonstrations of successful use of UAAs in generating a novel material.
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Aminoácidos/química , Elastina , Hidrogéis , Nanoestruturas , Peptídeos , Transição de FaseRESUMO
Surface modification is frequently used to tailor the interactions of nanoparticles with biological systems. In many cases, the chemical nature of the treatments employed to modify the biological interface (for example attachment of hydrophilic polymers or targeting groups) is the focus of attention. However, isolation of the fundamental effects of the materials employed to modify the interface are often confounded by secondary effects imparted by the underlying substrate. Herein, we demonstrate that polymer replica particles templated from degradable mesoporous silica provide a facile means to evaluate the impact of surface modification on the biological interactions of nanomaterials, independent of the substrate. Poly(ethylene glycol) (PEG), poly(N-(2 hydroxypropyl)methacrylamide) (PHPMA), and poly(methacrylic acid) (PMA) were templated onto mesoporous silica and cross-linked and the residual particles were removed. The resulting nanoparticles, comprising interfacial polymer alone, were then investigated using a range of in vitro and in vivo tests. As expected, the PEG particles showed the best stealth properties, and these trends were consistent in both in vitro and in vivo studies. PMA particles showed the highest cell association in cell lines in vitro and were rapidly taken up by monocytes in ex vivo whole blood, properties consistent with the very high in vivo clearance subsequently seen in rats. In contrast, PHPMA particles showed rapid association with both granulocytes and monocytes in ex vivo whole blood, even though in vivo clearance was less rapid than the PMA particles. Rat studies confirmed better systemic exposure for PEG and PHPMA particles when compared to PMA particles. This study provides a new avenue for investigating material-dependent biological behaviors of polymer particles, irrespective of the properties of the underlying core, and provides insights for the selection of polymer particles for future biological applications.
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Nanopartículas , Animais , Polietilenoglicóis , Polímeros , Ratos , Dióxido de Silício , Distribuição TecidualRESUMO
Pectin hydrogel particles (PHPs) were prepared by ionotropic gelation of low methylesterified pectin of Tanacetum vulgare L. with calcium ions. Wet PHPs prepared from TVF exhibited a smaller diameter and the lower weight as well as exhibited the best textural properties in terms of hardness and elasticity compared to the PHPs prepared from commercial low methylesterified pectin (CU701) used for comparison. Upon air drying, PHPs prepared from CU701 became small and dense microspheres whereas the dry PHPs prepared from TVF exhibited a drop-like shape. The morphology of dry PHPs determined by scanning electron microscopy revealed that the surface of the TVF beads exhibited fibred structures, whereas the PHPs prepared from CU701 exhibited a smooth surface. The characterization of surface roughness using atomic force microscopy indicated less roughness profile of the PHPs prepared from TVF than CU701. PHPs prepared from TVF were found to possess in vitro resistance to successive incubations in simulated gastric (SGF), intestinal (SIF), and colonic fluid (SCF) at 37 °C for 2, 4 and 18 h, respectively. The PHPs prepared from CU701 swelled in SGF and then lost their spherical shape and were fully disintegrated after 4 h of incubation in SIF. The PHPs from TVF, which were subjected to treatment with SGF, SIF and SCF, were found to adsorb microbial ß-glucuronidase (ßG) in vitro. The data obtained offered the prospect for the development of the PHPs from TVF as sorbents of colonic ßG for the inhibition of re-absorption of estrogens.