Search Results (56)

Functional recovery after traumatic brain injury (TBI) is hindered by progressive neurodegeneration resulting from neuroinflammation and other secondary injury processes. Dexamethasone (DX), a synthetic glucocorticoid, has been shown to reduce inflammation, but its systemic administration can cause a myriad of other medical issues. We aim to provide a local, sustained treatment of DX for TBI. Previously, we demonstrated that PEG-bis-AA/HA-DXM hydrogels composed of polyethyleneglycol-bis-(acryloyloxy acetate) (PEG-bis-AA) and dexamethasone-conjugated hyaluronic acid (HA-DXM) reduced secondary injury and improved motor functional recovery at 7 days post-injury (DPI) in a rat moderate controlled cortical impact (CCI) TBI model. In this study, we evaluated the effect of PEG-bis-AA/HA-DXM hydrogel on cognitive function and secondary injury at 14 DPI. Immediately after injury, hydrogel disks were placed on the surface of the injured cortex. Cognitive function was evaluated using the Morris Water Maze test, and secondary injury was evaluated by histological analysis. The hydrogel treatment group demonstrated significantly shorter latency to target, decreased distance to find the hidden target, increased number of target crossings, increased number of entries to the platform zone, and decreased latency to first entry of target zone compared to untreated TBI rats for probe test. We also observed reduced lesion volume, inflammatory response, and apoptosis in the hydrogel treatment group compared to the untreated TBI group. Full article

In this project, a new class of temperature- and pH-sensitive hydrogel consisting of N-isopropyl acrylamide (NIPAM), hydroxyethyl methacrylate (HEMA), and acrylamide (AAm) was prepared via a controlled route through the reversible addition–fragmentation chain-transfer (RAFT) polymerization process. Poly(ethyleneglycol) dimethacrylate (PEG-DMA) was used as a long-chain hydrophilic and biocompatible crosslinking agent. The hydrogel structure was confirmed by different characteristic techniques such as ¹H NMR, FT-IR, and SEC, and the morphology and particle diameters were checked via the scanning electron microscopy (SEM) and dynamic light scattering (DLS) methods. Afterward, the as-prepared hydrogel, poly(NIPAM-co-HEMA-co-AAm), was loaded with doxorubicin (DOX) to be used as a temperature- and pH-triggered delivery carrier. The prepared system released DOX slowly at 37 °C and neutral pH, but increased DOX release significantly at 42 °C and acidic pH. The anti-cancer efficiencies of free DOX, hydrogel, and the DOX–hydrogel conjugate were tested in vitro using human colorectal adenocarcinoma HT-29 cell lines. Cytotoxicity evaluation of free DOX compared with the DOX–hydrogel conjugate revealed that more cancer cells were killed with increasing concentration. Moreover, the DOX-mediated apoptosis and ROS levels showed the beneficial effects of poly(NIPAM-co-HEMA-co-AAm) hydrogel for cancer drug delivery. Generally, the results suggest that this system can be a potential candidate for designing drug delivery systems. Full article

Herein, a sensitive electrochemiluminescence (ECL) immunosensor is designed by immobilizing ruthenium-tagged immune complexes at flexible poly-ethylene-glycol (PEG) chains on the electrode surface, which offers more freedom for the collision of the ruthenium complex at the electrode during the initial ECL reaction. The electrochemical characterizations confirm the loose structure of the assembled layer with the immune complex, providing an increase in the current and the resultant enhanced ECL emissions. Comparing the sensors with the rigid structure, a 34-fold increase in the maximal ECL emission is recorded when PEG3400 is used as a linker. Using the optimized protocol, the prepared immunosensor exhibits a wide-ranging linear response to the model antibody (glutamate decarboxylase antibody) ranging from 10 pg/mL to 10 ng/mL. The detection limit is almost two orders lower than the value using the classic enzyme-linked immunosorbent assay, which offers a new design to enhance ECL emissions and the resultant analytical performance. Full article

Controlling protein crystallization processes is essential for improving downstream processing in biotechnology. This study investigates the combination of machine learning-based image analysis and in situ microscopy for real-time monitoring of protein crystallization kinetics. The experimental research is focused on the batch crystallization of an alcohol dehydrogenase from Lactobacillus brevis (LbADH) and two selected rational crystal contact mutants. Technical protein crystallization experiments were performed in a 1 L stirred crystallizer by adding polyethyleneglycol 550 monomethyl ether (PEG 550 MME). The estimated crystal volumes from online microscopy correlated well with the offline measured protein concentrations in solution. In addition, in situ microscopy was superior to offline data if amorphous protein precipitation occurred. Real-time image analysis provides the data basis for online estimation of important batch crystallization performance indicators like yield, crystallization kinetics, crystal size distributions, and number of protein crystals. Surprisingly, one of the LbADH mutants, which should theoretically crystallize more slowly than the wild type based on molecular dynamics (MD) simulations, showed better crystallization performance except for the yield. Thus, online monitoring of scalable protein crystallization processes with in situ microscopy and real-time image analysis improves the precision of crystallization studies for industrial settings by providing comprehensive data, reducing the limitations of traditional analytical techniques, and enabling new insights into protein crystallization process dynamics. Full article

The Turkevich method was optimized to prepare gold nanoparticles (AuNP) stabilized by polyethyleneglycol (PEG) for µCT. Using various independent modalities, we thoroughly characterized the optimized PEG-AuNPs. Here, we show that PEG-AuNPs are retained in the blood and provide a high contrast in the high-resolution µCT imaging of blood vessels and inner organs. The biodistribution is characterized by prolonged circulation in the blood and accumulation in the liver, spleen and skin. The accumulation of AuNP in the skin resulted in the blue discoloration of eyes and the whole skin. In vitro experiments using a leukemic monocyte THP-1 cell line model expressing high levels of NLRP3 demonstrated that the NLRP3inflammasome was not activated by PEG AuNP. Over 9 months, the mice were scanned by µCT and were in good health. Scans in mice using PEG-stabilized AuNPs in this study were sharper, with a higher contrast, when compared to a commercial contrasting agent at the same dose. The PEG-AuNPs were morphologically and chemically stable for at least two years when stored in the refrigerator. Full article

The general requirement of replacing petroleum-derived plastics with renewable resources is particularly challenging for new technologies such as the additive manufacturing of photocurable resins. In this work, the influence of mono- and bifunctional reactive diluents on the printability and performance of resins based on acrylated epoxidized soybean oil (AESO) was explored. Polyethylene glycol di(meth)acrylates of different molecular weights were selected as diluents based on the viscosity and mechanical properties of their binary mixtures with AESO. Ternary mixtures containing 60% AESO, polyethylene glycol diacrylate (PEGDA) and polyethyleneglycol dimethacrylate (PEG200DMA) further improved the mechanical properties, water resistance and printability of the resin. Specifically, the terpolymer AESO/PEG575/PEG200DMA 60/20/20 (wt.%) improved the modulus (16% increase), tensile strength (63% increase) and %deformation at the break (21% increase), with respect to pure AESO. The enhancement of the printability provided by the reactive diluents was proven by Jacobs working curves and the improved accuracy of printed patterns. The proposed formulation, with a biorenewable carbon content of 67%, can be used as the matrix of innovative resins with unrestricted applicability in the electronics and biomedical fields. However, much effort must be done to increase the array of bio-based raw materials. Full article

Additive manufacturing (AM) has become one of the most promising manufacturing techniques in recent years due to the geometric design freedom that this technology offers. The main objective of this study is to explore Composite Extrusion Modelling (CEM) with aluminium as an alternative processing route for aluminium alloys. This process allows for working with pellets that are deposited directly, layer by layer. The aim of the technique is to obtain aluminium alloy samples for industrial applications with high precision, without defects, and which are processed in an environmentally friendly manner. For this purpose, an initial and preliminary study using powder injection moulding (PIM), necessary for the production of samples, has been carried out. The first challenge was the design of a sustainable aluminium-based feedstock. The powder injection moulding technique was used as a first approach to optimise the properties of the feedstock through a combination of water-soluble polymer, polyethyleneglycol (PEG), and cellulose acetate butyrate (CAB) wich produces low CO₂ emissions. To do this, a microstructural characterisation was carried out and the critical solid loading and rheological properties of the feedstocks were studied. Furthermore, the debinding conditions and sintering parameters were adjusted in order to obtain samples with the required density for the following processes and with high geometrical accuracy. In the same way, the printing parameters were optimised for proper material deposition. Full article

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile. Full article

Adipose-derived stem cells (ADSCs) have incredible potential as an avenue to better understand and treat neurological disorders. While they have been successfully differentiated into neural stem cells and neurons, most such protocols involve 2D environments, which are not representative of in vivo physiology. In this study, human ADSCs were cultured in 1.1 kPa polyethylene-glycol 3D hydrogels for 10 days with B27, CultureOne (C1), and N2 neural supplements to examine the neural differentiation potential of ADSCs using both chemical and mechanical cues. Following treatment, cell viability, proliferation, morphology, and proteome changes were assessed. Results showed that cell viability was maintained during treatments, and while cells continued to proliferate over time, proliferation slowed down. Morphological changes between 3D untreated cells and treated cells were not observed. However, they were observed among 2D treatments, which exhibited cellular elongation and co-alignment. Proteome analysis showed changes consistent with early neural differentiation for B27 and C1 but not N2. No significant changes were detected using immunocytochemistry, potentially indicating a greater differentiation period was required. In conclusion, treatment of 3D-cultured ADSCs in PEG-based hydrogels with B27 and C1 further enhances neural marker expression, however, this was not observed using supplementation with N2. Full article

Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (~170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30–35 mV. Notably, Gelucire again produced the smallest particle size (211.1 ± 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (~235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity. Full article

Polymeric microparticles of polyethyleneglycol-polylactic acid-co-glycolic acid (PEG-PLGA) are widely used as drug carriers for a variety of applications due to their unique characteristics. Although existing techniques for producing polymeric drug carriers offer the possibility of achieving greater production yield across a wide range of sizes, these methods are improbable to precisely tune particle size while upholding uniformity of particle size and morphology, ensuring consistent production yield, maintaining batch-to-batch reproducibility, and improving drug loading capacity. Herein, we developed a novel scalable method for the synthesis of tunable-sized microparticles with improved monodispersity and batch-to-batch reproducibility via the coaxial flow-phase separation technique. The study evaluated the effect of various process parameters on microparticle size and polydispersity, including polymer concentration, stirring rate, surfactant concentration, and the organic/aqueous phase flow rate and volume ratio. The results demonstrated that stirring rate and polymer concentration had the most significant impact on the mean particle size and distribution, whereas surfactant concentration had the most substantial impact on the morphology of particles. In addition to synthesizing microparticles of spherical morphology yielding particle sizes in the range of 5–50 µm across different formulations, we were able to also synthesize several microparticles exhibiting different morphologies and particle concentrations as a demonstration of the tunability and scalability of this method. Notably, by adjusting key determining process parameters, it was possible to achieve microparticle sizes in a comparable range (5–7 µm) for different formulations despite varying the concentration of polymer and volume of polymer solution in the organic phase by an order of magnitude. Finally, by the incorporation of fluorescent dyes as model hydrophilic and hydrophobic drugs, we further demonstrated how polymer amount influences drug loading capacity, encapsulation efficiency, and release kinetics of these microparticles of comparable sizes. Our study provides a framework for fabricating both hydrophobic and hydrophilic drug-loaded microparticles and elucidates the interplay between fabrication parameters and the physicochemical properties of microparticles, thereby offering an itinerary for expanding the applicability of this method for producing polymeric microparticles with desirable characteristics for specific drug delivery applications. Full article

Morquio A disease is a genetic disorder resulting in N-acetylgalactosamine-6-sulfate sulfatase (GALNS) deficiency, and patients are currently treated with enzyme replacement therapy via weekly intravenous enzyme infusions. A means of sustained enzyme delivery could improve patient quality of life by reducing the administration time, frequency of hospital visits, and treatment cost. In this study, we investigated poly(ethylene-glycol) (PEG) hydrogels as a tunable, hydrolytically degradable drug delivery system for the encapsulation and sustained release of recombinant human GALNS (rhGALNS). We evaluated hydrogel formulations that optimized hydrogel gelation and degradation time while retaining rhGALNS activity and sustaining rhGALNS release. We observed the release of active rhGALNS for up to 28 days in vitro from the optimized formulation. rhGALNS activity was preserved in the hydrogel relative to buffer over the release window, and encapsulation was found to have no impact on the rhGALNS structure when measured by intrinsic fluorescence, circular dichroism, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In vivo, we monitored the retention of fluorescently labeled rhGALNS in C57BL/6 albino mice when administered via subcutaneous injection and observed rhGALNS present for up to 20 days when delivered in a hydrogel versus 7 days in the buffer control. These results indicate that PEG hydrogels are suitable for the encapsulation, preservation, and sustained release of recombinant enzymes and may present an alternative method of delivering enzyme replacement therapies that improve patient quality of life. Full article

Seed germination is a critical stage for survival during the life cycle of an individual plant. Genetic and environmental cues are integrated by individual seeds to determine germination, mainly achieved through regulation of the metabolism and signaling of gibberellins (GA) and abscisic acid (ABA), two phytohormones with antagonistic roles. Saline and drought conditions can arrest the germination of seeds and limit the seedling emergence and homogeneity of crops. This work aimed to study the function of BBX24, a B-Box transcription factor, in the control of germination of Arabidopsis thaliana seeds imbibed in saline and osmotic conditions. Seeds of mutant and reporter GUS lines of BBX24 were incubated at different doses of NaCl and polyethylene-glycol (PEG) solutions and with ABA, GA and their inhibitors to evaluate the rate of germination. We found that BBX24 promotes seed germination under moderated stresses. The expression of BBX24 is inhibited by NaCl and PEG. In addition, ABA suppresses BBX24-induced seed germination. Additional experiments suggest that BBX24 reduces ABA sensitivity, improving NaCl tolerance, and increases GA sensitivity in seeds imbibed in ABA. In addition, BBX24 inhibits the expression of ABI3 and ABI5 and genetically interacts upstream of HY5 and ABI5. This study demonstrates the relevance of BBX24 to induce drought and salinity tolerance in seed germination to ensure seedling emergence in sub-optimal environments. Full article

Drought is one of the most detrimental factors that causes significant effects on crop development and yield. However, the negative effects of drought stress may be alleviated with the aid of exogenous melatonin (MET) and the use of plant-growth-promoting bacteria (PGPB). The present investigation aimed to validate the effects of co-inoculation of MET and Lysinibacillus fusiformis on hormonal, antioxidant, and physio-molecular regulation in soybean plants to reduce the effects of drought stress. Therefore, ten randomly selected isolates were subjected to various plant-growth-promoting rhizobacteria (PGPR) traits and a polyethylene-glycol (PEG)-resistance test. Among these, PLT16 tested positive for the production of exopolysaccharide (EPS), siderophore, and indole-3-acetic acid (IAA), along with higher PEG tolerance, in vitro IAA, and organic-acid production. Therefore, PLT16 was further used in combination with MET to visualize the role in drought-stress mitigation in soybean plant. Furthermore, drought stress significantly damages photosynthesis, enhances ROS production, and reduces water stats, hormonal signaling and antioxidant enzymes, and plant growth and development. However, the co-application of MET and PLT16 enhanced plant growth and development and improved photosynthesis pigments (chlorophyll a and b and carotenoids) under both normal conditions and drought stress. This may be because hydrogen-peroxide (H₂O₂), superoxide-anion (O²⁻), and malondialdehyde (MDA) levels were reduced and antioxidant activities were enhanced to maintain redox homeostasis and reduce the abscisic-acid (ABA) level and its biosynthesis gene NCED3 while improving the synthesis of jasmonic acid (JA) and salicylic acid (SA) to mitigate drought stress and balance the stomata activity to maintain the relative water states. This may be possible due to a significant increase in endo-melatonin content, regulation of organic acids, and enhancement of nutrient uptake (calcium, potassium, and magnesium) by co-inoculated PLT16 and MET under normal conditions and drought stress. In addition, co-inoculated PLT16 and MET modulated the relative expression of DREB2 and TFs bZIP while enhancing the expression level of ERD1 under drought stress. In conclusion, the current study found that the combined application of melatonin and Lysinibacillus fusiformis inoculation increased plant growth and could be used to regulate plant function during drought stress as an eco-friendly and low-cost approach. Full article

The restoration of cartilage damage is a slow and not always successful process. Kartogenin (KGN) has significant potential in this space—it is able to induce the chondrogenic differentiation of stem cells and protect articular chondrocytes. In this work, a series of poly(lactic-co-glycolic acid) (PLGA)-based particles loaded with KGN were successfully electrosprayed. In this family of materials, PLGA was blended with a hydrophilic polymer (either polyethyleneglycol (PEG) or polyvinylpyrrolidone (PVP)) to control the release rate. Spherical particles with sizes in the range of 2.4–4.1 µm were fabricated. They were found to comprise amorphous solid dispersions, with high entrapment efficiencies of >93%. The various blends of polymers had a range of release profiles. The PLGA-KGN particles displayed the slowest release rate, and blending with PVP or PEG led to faster release profiles, with most systems giving a high burst release in the first 24 h. The range of release profiles observed offers the potential to provide a precisely tailored profile via preparing physical mixtures of the materials. The formulations are highly cytocompatible with primary human osteoblasts. Full article