Study of interaction between polyethylene glycol and chitosan by viscosity method

The covalent binding of proteins with polyethylene glycol (PEG) molecules is a valuable tool to extend the half-life of many biotherapeutics, including factor VIII (FVIII) products to treat patients with haemophilia A. Although PEG has low toxicity, accumulation of large PEG molecules (>20–30 kDa) with long-term exposure is a potential concern. Thus, it is important to determine whether sufficient excretion processes exist for PEG molecules used in biotherapeutics. BAY 94-9027 is an extended–half-life FVIII product modified through addition of a 60-kDa (branched: dual 30-kDa) PEG molecule. BAY 1025662 is the 60-kDa PEG moiety used for PEGylation of BAY 94-9027. This study investigated the pharmacokinetic (PK) properties, distribution, and excretion of BAY 1025662 in rats in order to predict estimated 60-kDa PEG PK properties in patients. Plasma concentrations in male rats after a single 11-mg/kg intravenous dose of BAY 1025662 (approximating the cumulative PEG-60 exposure in patients during 30 years of BAY 94-9027 treatment) decreased with an initial half-life of 119 h (5 days) in the interval of 114–336 h post administration. Single-dose mass balance studies using radiolabeled BAY 1025662 ([prop-14C]BAY 1025662) showed that 30.4% of radioactivity was excreted within 1 week and 79.1% by Day 168 (primarily in urine). The terminal half-life of radioactivity elimination was approximately 24 days in blood and plasma and was 31–68 days in the majority of other organs up to Day 168. Elimination was nearly complete at the end of the experiment on Day 168; only ~4% of residual radioactivity was present in the animal body. There was no irreversible binding of radioactivity to any tissues and no penetration of the blood-brain barrier. Based on these results, very low steady-state concentrations of 60-kDa PEG were predicted in patients treated with BAY 94-9027, and the validity of these predictions was supported by clinical studies in which almost all 179 patients receiving BAY 94-9027 for prophylaxis had undetectable PEG in plasma for up to >5 years; those with detectable PEG levels demonstrated concentrations within the predicted range. These combined preclinical and clinical observations suggest that excretion processes are in place for high-molecular-weight PEGs such as the PEG-60 moiety used in BAY 94-9027.

Preferential hydration and solubility of proteins in aqueous solutions of polyethylene glycol

Physiology of soybean as affected by PEG-induced drought stress

The study aimed to develop stable single-walled carbon nanotube (SWCNT) dispersions in water that exhibit low protein adsorption in biological media, entrap Memantine,and release the drug in a controlled manner. Specifically, SWCNTs were functionalized, initially oxidized, and then non-covalently conjugated with pyrene methoxy polyethylene glycols (PEG). Dynamic light scattering, Raman spectroscopy, and Fourier-transform infrared spectroscopy were used to evaluate various physicochemical properties of PEG functionalized SWCNTs (PEGSWCNTs). A D-optimal design, utilizing JMP Pro 16, was employed to design the experiment and investigate the effects of oxidation time and PEG concentration on the physicochemical properties of SWCNT dispersions. The optimal dispersions exhibited hydrodynamic particle sizes, polydispersity indices, and zeta potentials ranging from 157.5 to 204.4nm, 0.231 to 0.255, and -27.8 to -18.8mV, respectively. The interaction between serum proteins and PEGSWCNTs was evaluated using dynamic light scattering, bicinchoninic acid, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The serum protein-SWCNT interaction was significantly reduced due to the presence of PEGs, depending on PEG concentrations, the ratio of long-chain PEG molecules to short-chain PEG molecules, and the physicochemical properties of PEGSWCNT dispersions. Finally, Memantine was incorporated into the optimal PEGSWCNT dispersions. The entrapmentefficiency, drugloading, and drugrelease from the dispersions were evaluated using gas chromatography with flame ionization detection (GC/FID). The results indicated that PEGSWCNT particles could entrap Memantine. The in vitrodrug release profile exhibited an extended release over 3 to 7h, with a significant burst release occurring in the first hour (more than 50%). Higher PEG density and a higher PEG20K/2K ratio exhibited slower drug release rates. The release profiles of the formulations using 40% PEG were fitted to the Weibull model, indicating that Memantine release from the SWCNT dispersions followed a Fickian diffusion mechanism.

Polymer-protein interactions are crucial for determining the activity of both polymer and protein for many bio-related applications. Poly(ethylene glycol) (PEG) as a well-known antifouling material is often coated on surfaces to form highly solvated brushes, which exhibit excellent protein-repellent properties. However, unlike surface-induced antifouling effects, little is known about the intrinsic PEG-protein interactions in aqueous solution, which is an important yet neglected problem. Here, we investigate the interactions between PEG and proteins in aqueous solution using fluorescence spectroscopy, atomic force microscopy (AFM), and nuclear magnetic resonance (NMR). Two important characteristics, molecular weight of PEG and mass ratio of PEG : protein, are examined to determine the effect of each on PEG-protein interactions as well as binding characteristics between PEG and proteins. In contrast to too long and too short PEG chains, collective results have shown that PEG with optimal molecular weight (MW) is more capable of interacting with proteins, which induces the conformational change of proteins through more stable binding sites and stronger interactions with long chain PEG. Enhanced PEG-protein interactions are likely due to the change of hydrophilicity to amphiphilicity of PEG with increasing MWPEG. In contrast to almost none or weak interactions of PEG surfaces with proteins, this work provides new evidence to demonstrate the existence of interactions between PEG and proteins in aqueous solution, which is important not only for better understanding of the structure-activity relationship of PEG both in solution and on surfaces, but also for the rational design of new PEG-based materials for specific applications.

This study reports for the first time the usage of polyethylene glycol (PEG) as the capping agent to control mesoporous shell thickness of hollow mesoporous silica nanoparticles (HMSN)—a promising nanocarrier. HMSN was synthesized with hard template method and PEG with different molecular weights and concentrations would be added at the mesoporous coating. The samples dSiO 2 @MSN synthesized with and without PEG were analyzed DLS, field‐emission scanning electron microscopy, Brunauer–Emmett–Teller and Barrett–Joyner–Halenda to characterize their mesoporous shells. Meanwhile transmission electron microscope, Zeta potential, energy dispersive X‐ray spectroscopy, Fourier‐transform infrared, loading capacity, release profile and cytotoxicity analysis was conducted to characterize HSMNs. As PEG's molecular weight or concentration increased, the mesoporous shell thickness gradually raised. Particles synthesized in the presence of 2% PEG 6000 retained the monodispersed spherical morphology with a particle diameter of 95.40 nm and a mesoporous shell thickness of 14.40 nm, which was about 7.0 nm thicker. dSiO 2 @MSN‐P owned equal mesopore diameter and higher surface area compared to dSiO 2 @MSN‐0. HMSN‐P showed similar loading capacity but better sustained release profile than HMSN‐0. Moreover, both HMSN‐0 and HMSN‐P performed as biocompatible materials. This study would contribute a simple and effective method to control the shell thickness of HMSN with PEG for drug delivery applications.

The adsorption kinetics of polyethylene glycol (PEG) during Cu electroless deposition was investigated in real-time by measuring the open-circuit potential (OCP) and mass change of a Cu electrode. The addition of PEG during the deposition caused an OCP decrease with a reduction in the deposition rate. It was found that the adsorption of PEG blocked active sites for the adsorption of formaldehyde, a reducing agent, resulting in the suppression effect. The adsorption kinetics of PEG was strongly dependent on the concentration and diffusion coefficient which is directly related to the molecular weight of PEG. The diffusion-controlled adsorption was observed when PEG concentration was low. At high PEG concentrations, the adsorption kinetics was adsorption-controlled when the PEG molecular weight was low and diffusion-controlled when the PEG had a high molecular weight. The strength of the suppression effect was also affected by the molecular weight of PEG: increasing the molecular weight enhanced the suppression effect.

Influence of magnetic field on aqueous two-phase extraction of horse ferritin in the polyethylene glycol/hydroxyethyl starch system

BackgroundType-1 Interferons (IFN) are known to elicit both direct antitumor effects as well as modulate tumor microenvironment (TME) to induce antitumor immune responses. Combination of IFNa with PD-1 blockade has...

Aqueous two-phase extraction of wedelolactone from Eclipta alba was studied using the polymer-salt system. The system consisted of polyethylene glycol (PEG) as a top phase (polymer) and sodium citrate as a bottom phase (salt). Process parameters such as PEG concentration, PEG molecular weight, salt concentration, and pH have been optimized using response surface methodology (RSM) with the help of central composite design (CCD). The optimized conditions for aqueous two-phase system (ATPS), in the case of one factor at a time approach, were found as PEG 6000, PEG concentration 18% (w/v), salt concentration 16% (w/v), and pH 7; with maximum extraction yield of 6.52 mg/g. While, RSM studies showed maximum extraction yield of 6.73 mg/g with the optimized parameters as PEG 6000, PEG concentration 18% (w/v), salt concentration 17.96% (w/v), and pH 7. ATPS was found to give a 1.3 fold increase in the extraction yield of wedelolactone as compared to other conventional extraction methods.

Viscoelastic signature of physisorbed macromolecules at the solid–liquid interface

The purpose of this study was to explore the cryoprotection mechanisms of high molecular weight polyethylene glycols (PEGs) (eg, PEG 4000 and PEG 8000) on lactate dehydrogenase (LDH). Ultraviolet activity assays, circular dichroism (CD) spectroscopy, gel filtration, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), (14)C-PEG 4000 labeling and binding, and cryostage microscopic study were conducted. Different molecular weights and concentrations of PEGs in LDH formulations were treated by freeze-thawing. Higher molecular weights and concentrations of PEGs in LDH-PEG formulations obtained better activity and secondary structure recoveries of LDH after freeze-thawing. Insoluble aggregation of LDH was not observed in gel filtration studies. SDS-PAGE results suggested surface characteristic modifications of LDH by the larger molecular weight PEGs. The 14C-PEG 4000 labeling and binding study showed extensive nonspecific interactions between the PEG 4000 and LDH molecules in a concentration-dependent manner. The bound LDH-PEG 4000/free PEG 4000 ratio increased when LDH or PEG 4000 concentrations increased. Cryostage microscopic study showed that PEG 8000 delayed the ice crystallization and eutectic transition of LDH formulation. It appeared that multiple mechanisms were at work during PEGs' cryoprotection of LDH. It was unclear whether the delayed eutectic characteristics of PEGs contributed to LDH cryoprotection. The favorable interaction, rather than preferential exclusion, between LDH and PEGs (eg, 4000) cryoprotected LDH.

Green, recyclable and high latent heat form-stable phase change composites supported by cellulose nanofibers for thermal energy management

Optimization of thaumatin extraction by aqueous two-phase system (ATPS) using response surface methodology (RSM)

The aim of this study was to develop fluconazole in an ultrapure polyvinyl alcohol (PVA) hydrogel able to deliver the drug in a sustained release pattern for local treatment of skin fungal infections. The topical fluconazole hydrogels were prepared using PVA hydrogels physically cross-linked by freeze–thaw technique. Polyethylene glycol (PEG) was added as a hydrophilic excipient as a release enhancer of fluconazole. The effects of PVA molecular weight, PEG molecular weight, and PEG concentration were studied using a 2 × 4 × 2 factorially designed experiment. The selected fluconazole hydrogel proved to be physically stable over a period of 6 months and to be effective in the topical treatment of cutaneous candidiasis. Therefore, it could be concluded that the formula composed of 10% PVA 205000 and 1.5% PEG 4000 and 2% fluconazole and prepared by three cycles of freezing, and thawing is very promising in the local treatment of skin fungal infection as an alternative to the systemic use of fluconazole.