Poly(Ethylene glycol)-based backbones with high peptide loading capacities.
Ontology highlight
ABSTRACT:
SUBMITTER: O'Connor A
PROVIDER: S-EPMC6270934 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Nanotubes were prepared by self-assembly of the copolymer using co-solvent evaporation method. The biocompatibility of the nanotubes was assessed in comparison with spherical micelles and filomicelles prepared from poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PEG-PLGA) and poly(ethylene glycol)-poly(L-lactide) (PEG-PLA), respectively. Several aspects of biocompatibility of the aggregates were considered, including agar diffusion and MTT assay, release of cytokines, hemolysis, protein adsorption, dynamic clotting in vitro, and Zebrafish embryonic compatibility in vivo. The nanotubes present good cell compatibility and blood compatibility in vitro, and almost no toxicity towards Zebrafish embryos development in vivo. Furthermore, dual-loading of hydrophilic cisplatin and hydrophobic paclitaxel was achieved in the nanotubes with high loading content and loading efficiency. The release of both drugs was slower from dual-loaded nanotubes than from single-loaded ones, but the total amount of released drugs in higher for dual-loaded nanotubes than from single-loaded ones. Cellular uptake and inhibition tests showed that the nanotubes were successfully taken up by tumor cells and effectively inhibited cell growth. It is thus concluded that PEG-PLA-PEG nanotubes with outstanding biocompatibility could be promising for co-delivery of hydrophilic and hydrophobic agents in combination cancer therapy.
| S-EPMC6978636 | biostudies-literature
Project description:Poly(ethylene glycol) (PEG) hydrogels functionalized with peptide moieties have been widely used in regenerative medicine applications. While many studies have suggested the importance of affinity binding within PEG hydrogels, the relationships between the structures of the peptide motifs and their binding to protein therapeutics remain largely unexplored, especially in the recently developed thiol-acrylate photopolymerization systems. Herein, we employ Förster resonance energy transfer (FRET) and thiol-acrylate photopolymerizations to investigate how the architectures of affinity peptides in crosslinked hydrogels affect their binding to diffusible proteins. The binding between diffusible streptavidin and biotinylated peptide immobilized to PEG hydrogel network was used as a model system to reveal the interplay between affinity binding and peptide sequences/architectures. In addition, we design peptides with different structures to enhance affinity binding within PEG hydrogels and to provide tunable affinity-based controlled delivery of basic fibroblast growth factor (bFGF). This study demonstrates the importance of affinity binding in controlling the availability of hydrogel-encapsulated proteins and provides strategies for enhancing affinity binding of protein therapeutics to bound peptide moieties in thiol-acrylate photopolymerized PEG hydrogels. The results presented herein should find useful on the design and fabrication of hydrogels to retain and sustained release of growth factors for promoting tissue regeneration.
| S-EPMC2818180 | biostudies-literature
Project description:Clickable poly(ethylene glycol) (PEG) derivatives are used with two sequential aqueous two-phase systems to produce microsphere-based scaffolds for cell encapsulation. In the first step, sodium sulfate causes phase separation of the clickable PEG precursors and is followed by rapid geleation to form microspheres in the absence of organic solvent or surfactant. The microspheres are washed and then deswollen in dextran solutions in the presence of cells, producing tightly packed scaffolds that can be easily handled while also maintaining porosity. Endothelial cells included during microsphere scaffold formation show high viability. The clickable PEG-microsphere-based cell scaffolds open up new avenues for manipulating scaffold architecture as compared with simple bulk hydrogels.
| S-EPMC3774304 | biostudies-literature
Project description:Transdermal delivery of therapeutic biomolecules (including peptides) can avoid enzymatic digestion that occurs in the oral route. (Polyethylene glycol) diacrylate (PEGDA)-based microneedles, with good biocompatibility, are easily fabricated through photo-polymerization with a precisely controlled structure. It has successfully been used for the transdermal delivery of small molecule drugs such as 5-fluorouracil. However, the delivery of peptide-based therapeutics using this platform is seldom reported. This is because of the potential damage to the peptide during the photo-polymerization process of PEGDA. Herein, we introduce a method to load PEGDA microneedles with peptides without compromising peptide potency. Using gap junction inhibitor (Gap 26) as an example, the peptide was loaded into PEGDA microneedles through the swelling effect of PEGDA in the aqueous solution. The peptide-loaded microneedles were applied to a keloid scar model and exhibited inhibition expression of collagen I, a predominant marker of keloid scar, demonstrating its potential therapeutic effects.
| S-EPMC5689501 | biostudies-literature
Project description:Amphiphilic polymers can be used to form micelles to deliver water-insoluble drugs. A biodegradable poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)-PEG triblock copolymer was developed that is useful for drug delivery. It was shown to successfully encapsulate and pH-dependently release a water-insoluble, small molecule anticancer drug, verteporfin. PEG-PBAE-PEG micelle morphology was also controlled through variations to the hydrophobicity of the central PBAE block of the copolymer in order to evade macrophage uptake. Spherical micelles were 50 nm in diameter, while filamentous micelles were 31 nm in width with an average aspect ratio of 20. When delivered to RAW 264.7 mouse macrophages, filamentous micelles exhibited a 89% drop in cellular uptake percentage and a 5.6-fold drop in normalized geometric mean cellular uptake compared to spherical micelles. This demonstrates the potential of high-aspect-ratio, anisotropically shaped PEG-PBAE-PEG micelles to evade macrophage-mediated clearance. Both spherical and filamentous micelles also showed therapeutic efficacy in human triple-negative breast cancer and small cell lung cancer cells without requiring photodynamic therapy to achieve an anticancer effect. Both spherical and filamentous micelles were more effective in killing lung cancer cells than breast cancer cells at equivalent verteporfin concentrations, while spherical micelles were shown to be more effective than filamentous micelles against both cancer cells. Spherical and filamentous micelles at 5 and 10 ?M respective verteporfin concentration resulted in 100% cell killing of lung cancer cells, but both micelles required a higher verteporfin concentration of 20 ?M to kill breast cancer cells at the levels of 80% and 50% respectively. This work demonstrates the potential of PEG-PBAE-PEG as a biodegradable, anisotropic drug delivery system as well as the in vitro use of verteporfin-loaded micelles for cancer therapy.
| S-EPMC6249031 | biostudies-literature
Project description:Polyethylene glycol (PEG) is one of the most common polymer contaminations in MS samples. At present, the detection of PEG and other polymers relies largely on manual inspection of raw data which is laborious and frequently difficult due to sample complexity and retention characteristics of polymer species in reversed phase chromatography. We developed a new strategy for the automated identification of PEG molecules from MSMS data using protein identification algorithms in combination with a database containing “PEG-proteins”. Through definition of variable modifications, we extend the approach for the identification of commonly used PEG-based detergents. We exemplify the identification of different types of polymers by static nanoESI-MSMS analysis of pure detergent solutions and data analysis using Mascot. Analysis of LC-MSMS runs of a PEG contaminated sample by Mascot identified 806 PEG-spectra originating from four PEG species using a defined set of modifications covering PEG and common PEG-based detergents. Further characterization of the sample for unidentified PEG species using error tolerant and mass tolerant searches resulted in identification of 3409 and 3187 PEG related MSMS spectra, respectively. We further demonstrate the applicability of the strategy for Protein Pilot and MaxQuant.
2018-05-28 | PXD009376 | Pride
Project description:A novel pH-sensitive polymeric micellar system composed of poly(L-histidine)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) block copolymers was studied by dynamic/static light scattering, spectrofluorimetry and differential scanning calorimetry. The mixed micelles displayed ultra Ph Sensitivity Which Could Be Tuned By Varying The Mixing Ratio Of The Two Polymers. In Particular, Mixed Micelles Composed Of 25 Wt.% Poly(L-lactide)-b-poly(ethylene glycol) exhibited desirable pH dependency which could be used as a drug delivery system that selectively targeted the extracellular pH of acidic solid tumors. Micelles were quite stable from pH 7.4 to 7.0 but underwent a two-stage destabilization as pH decreased further. A significant increase in size and aggregation number was observed when pH dropped to 6.8. Further disruption of the micelle core eventually caused phase separation in the micelle core and dissociation of ionized poly(L-histidine)-b-poly(ethylene glycol) molecules from the micelles as pH decreased to 6.0. Increased electrostatic repulsions which arise from the progressive protonation of imidazole rings overwhelming the hydrophobic interactions among uncharged neutral blocks is considered to be the mechanism for destabilization of the micelle core.
| S-EPMC2276666 | biostudies-literature
Project description:Defects in a polymer network complicate an accurate calculation of structural parameters such as the molar mass between cross-links M c, typically obtained from experimental swelling data. In this paper the formation and structure of poly(ethylene glycol) (PEG)-based polyurethane networks containing PEG-mono methyl ether dangling chains are studied. The phantom network model can describe the swelling behavior of these networks only when a composition-dependent interaction parameter is used and the formation of allophanates is accounted for. A clear transition in the network formation is found at the PEG network precursor molar mass at which entanglements are formed in the melt. Correction factors based on structure calculations using the Miller-Macosko-Vallés probability approach are proposed and validated for an accurate calculation of the M c of these defect-containing networks. This provides a new approach for studies that requires an accurate estimate of the M c, only based on experimentally straightforward swelling experiments.
| S-EPMC7017371 | biostudies-literature
Project description:The elastic modulus of the extracellular matrix is a dynamic property that changes during various biological processes, such as disease progression or wound healing. Most cell culture platforms, however, have traditionally exhibited static properties, making it necessary to replate cells to study the effects of different elastic moduli on cell phenotype. Recently, much progress has been made in the development of substrates with mechanisms for either increasing or decreasing stiffness in situ, but there are fewer examples of substrates that can both stiffen and soften, which may be important for simulating the effects of repeated ECM injury and resolution. In the work presented here, poly(ethylene glycol)-based hydrogels reversibly stiffen and soften with multiple light stimuli via photoisomerization of an azobenzene-containing cross-linker. Upon irradiation with cytocompatible doses of 365 nm light (10 mW/cm(2), 5 min), isomerization to the azobenzene cis configuration leads to a softening of the hydrogel up to 100-200 Pa (shear storage modulus, G'). This change in gel properties is maintained over a time scale of several hours due to the long half-life of the cis isomer. The initial modulus of the gel can be recovered upon irradiation with similar doses of visible light. With applications in mechanobiology in mind, cytocompatibility with a mechanoresponsive primary cell type is demonstrated. Porcine aortic valvular interstitial cells were encapsulated in the developed hydrogels and shown to exhibit high levels of survival, as well as a spread morphology. The developed hydrogels enable a route to the noninvasive control of substrate modulus independent of changes in the chemical composition or network connectivity, allowing for investigations of the effect of dynamic matrix stiffness on adhered cell behavior.
| S-EPMC4547937 | biostudies-literature
Project description:Hydrogel nanoparticles (also known as nanogels) have been utilized for a wide range of applications including analytics, sensors, drug delivery, immune engineering, and biotechnology. While these types of nanoparticles can be characterized using standard colloidal characterization techniques, degradation profiles typically must be inferred from those of bulk gels with the same formulation, typically by applying swelling ratios and rheological measurements that tend to severely underestimate nanoparticle degradation rates. Herein, we present an analysis of the degradation via ester hydrolysis of poly(ethylene glycol) diacrylate (PEGDA)-based hydrogel nanoparticles in water, varied pH conditions, and redox environments. We perform this characterization using thermogravimetric analysis and mass spectrometry to analyze rates of degradation and products released, respectively, and compare results to those for equivalent bulk gel formulations. Our findings show that PEGDA-based nanoparticles display significant mass loss over time accompanied by negligible changes in hydrodynamic diameter, indicating a bulk mode of degradation. Nanoparticle mass loss occurs at a much higher rate than for bulk gels under comparable incubation conditions, confirming that bulk gel degradation serves as a poor surrogate for nanoparticle degradation. We further demonstrate that the incorporation of other diacrylate-based co-monomers drastically accelerates nanoparticle degradation rates. Through formulation considerations of co-monomer content and weight percent of PEGDA, we demonstrate the ability to tune the degradation rates of PEGDA-based nanoparticles on a range of hours to weeks. These findings highlight critical design considerations for enhancing the tunability and utility of PEGDA hydrogel nanoparticles and introduce a rigorous framework for the characterization of nanogel degradation.
| S-EPMC7678750 | biostudies-literature