High Molecular Weight Polyethylene Glycol Research Articles

Polyethylene glycol hypersensitivity, patient outcomes in a 7-year retrospective study

BackgroundImmediate IgE-mediated hypersensitivity reactions to polyethylene glycol (PEG) are rare. Our understanding of PEG hypersensitivity is limited. ObjectiveTo evaluate the clinical characteristics and investigation outcomes of the largest cohort of patients with PEG allergy reported. MethodsA total of 44 patients investigated for suspected PEG allergy across 4 United Kingdom tertiary allergy centers between October 2013 and December 2020 were studied. Clinical characteristics, index reaction, and approaches to and outcomes of allergy investigations were analyzed. ResultsPEG hypersensitivity was confirmed in 42 of 44 cases. Macrogol laxatives were the most common index drugs reported (23%), followed by depo-medroxyprogesterone (19%), oral penicillin V (10%), and depo-methylprednisolone (10%). In general, 61% experienced grade III anaphylaxis. Intradermal testing (IDT) increased the diagnostic sensitivity from 51% to 85%. Five patients experienced systemic reactions during IDT. Of the 5 patients, 2 were skin prick test positive to a high molecular weight PEG. Three patients with negative skin test results had positive drug provocation test results. Seven patients with PEG allergy reported tolerance to H1-antihistamines containing PEG. Administration of messenger RNA COVID-19 or Oxford/AstraZeneca COVID-19 vaccines was tolerated in all 16 patients to whom they were administered. ConclusionPEG hypersensitivity is an uncommon cause of drug-induced anaphylaxis. Four index drugs accounted for two-thirds of the cases, and reactions to these drugs should prompt PEG hypersensitivity investigations. PEG IDT increases diagnostic yield. The role of skin prick test with higher molecular weight PEGs requires further attention. Further studies are required to understand PEG thresholds and PEG equivalent doses of various administration routes. COVID-19 vaccines were tolerated by all exposed.

PETR: A novel peristaltic mixed tubular bioreactor simulating human colonic conditions.

A novel bioreactor simulating human colonic conditions for in vitro cultivation of intestinal microbiota is presented. The PEristaltic mixed Tubular bioReactor (PETR) is modular designed and periodically kneaded to simulate intestinal peristalsis. The reactor is introduced, characterized from a bioprocess engineer's perspective and discussed in its ability to mimic colon conditions. PETR provides physiological temperature and appropriate anaerobic conditions, simulates intestinal peristalsis, and has a mean residence time of 32.8 ± 0.8 h comparable to the adult human colon. The single-tube design enables a time-constant and longitudinally progressive pH gradient from 5.5 to 7.0. Using a dialysis liquid containing high molecular weight polyethylene glycol, the integrated dialysis system efficiently absorbs short chain fatty acids (up to 60%) and water (on average 850 mL d-1 ). Cultivation of a typical gut bacterium (Bifidobacterium animalis) was performed to demonstrate the applicability for controlled microbiota cultivation. PETR is unique in combining simulation of the entire colon, peristaltic mixing, dialytic water and metabolite absorption, and a progressive pH gradient in a single-tube design. PETR is a further step to precise replication of colonic conditions in vitro for reliable and reproducible microbiota research, such as studying the effect of food compounds, prebiotics or probiotics, or the development and treatment of infections with enteric pathogens, but also for further medical applications such as drug delivery studies or to study the effect of drugs on and their degradation by the microbiota.

Unraveling the cytotoxicity and cellular uptake of low, medium and high molecular weight polyethylene glycol polymers in MCF-7 cells by green UPLC-MS/MS methods

Unraveling the cytotoxicity and cellular uptake of low, medium and high molecular weight polyethylene glycol (PEG) in cells is important for evaluation of therapeutic efficacy and toxicity of PEGylated drug delivery systems. In this study, cellular uptake of PEG600, PEG2K, PEG4K and PEG10K in MCF-7 cells was first studied by an UPLC-MS/MS assay coupled with collision induced dissociation (CID) in source technique. The CID of PEG in source with high values of declustering potentials generates numerous PEG-related product ions. These PEG-related fragment ions can be further broken into specific product ions in the collision cell as alternative ions for detection of PEG. The quantification of PEG was finally performed with the MRM transition (m/z 221.0 → 89.0). The experimental results indicated that the toxicity of PEG600, PEG2K, PEG4K and PEG10K was not significant at concentrations of 5–1200 μg/mL and the amounts of PEG polymers entry into MCF-7 cells at was small. The greenness of the developed analytical methods was also assessed by Analytical Eco-Scale, Analytical Greenness calculator (AGREE) and Green Analytical Procedure Index (GAPI) in this study.

Chain entanglement-driven tough, fatigue-resistant PEG-based injectable hydrogel adhesive for joint skin wound healing

The development of effective wound dressings that can withstand the frequent movement and stretching of joint skin wounds remains a significant challenge. Traditional wound dressings are prone to damage or shedding, which increases the risk of bacterial infection and delays wound healing. To address this issue, a new type of injectable, stretchable, low hysteresis, and fatigue-resistant hydrogel (LZM/PEG) adhesive has been designed for wound healing in movable parts. The hydrogel is formed through the flexible chain entanglement of high molecular weight polyethylene glycol functionalized by Succinimide Carbonate (SC-PEG-SC) and Amidation crosslinking between LZM-NH2 and SC-PEG-SC. The long-chain of SC-PEG-SC enables the hydrogel to penetrate the surface of the target tissue, generating physical entanglements and covalent bonds with functional groups in the matrix, enabling close fitting of joint skin and wound healing without the need of secondary fixation. In a neck trauma model of full-thickness skin defect in vivo, the hydrogel dressing significantly promoted wound healing with milder inflammation, higher granulation tissue thickness and collagen disposition, demonstrating its potential for joint skin wound treatment in clinics. Overall, the LZM/PEG hydrogel is capable of adapting to the frequent movement of joint, promoting healing of joint skin wounds, which makes it a promising approach for joint skin wound treatment.

Continuous Monitoring of the Hydration Behavior of Hydrophilic Matrix Tablets Using Time-Domain NMR.

Time-domain NMR (TD-NMR) was used for continuous monitoring of the hydration behavior of hydrophilic matrix tablets. The model matrix tablets comprised high molecular weight polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC), and polyethylene glycol (PEG). The model tablets were immersed in water. Their T2 relaxation curves were acquired by TD-NMR with solid-echo sequence. A curve-fitting analysis was conducted on the acquired T2 relaxation curves to identify the NMR signals corresponding to the nongelated core remaining in the samples. The amount of nongelated core was estimated from the NMR signal intensity. The estimated values were consistent with the experiment measurement values. Next, the model tablets immersed in water were monitored continuously using TD-NMR. The difference in hydration behaviors of the HPMC and PEO matrix tablets was then characterized fully. The nongelated core of the HPMC matrix tablets disappeared more slowly than that of the PEO matrix tablets. The behavior of HPMC was significantly affected by the PEG content in the tablets. It is suggested that the TD-NMR method has potential to be utilized to evaluate the gel layer properties, upon replacement of the immersion medium: purified (nondeuterated) water is replaced with heavy (deuterated) water. Finally, drug-containing matrix tablets were tested. Diltiazem hydrochloride (a highly water-soluble drug) was employed for this experiment. Reasonable in vitro drug dissolution profiles, which were in accordance with the results from TD-NMR experiments, were observed. We concluded that TD-NMR is a powerful tool to evaluate the hydration properties of hydrophilic matrix tablets.

Low and High Molecular Weight Polyethylene Glycol as A Treating and Coupling Agent in High Density Polyethylene/Date Palm Tree Fiber Composites

nical properties and water absorption (WA) behavior of high density polyethylene/date palm tree fiber (HDPE/DPTF) composites were investigated. Two different parts of the date palm tree (mesh and leaflets) were used. The focus was on studding the combination effect of using both low and/or high molecular weight polyethylene glycol (PEG) as a treatment and coupling agent, respectively on shore D hardness, impact strength and water absorption behavior of the composites. Morphological properties of the prepared composites were also investigated. Results showed that treating the fibers with low molecular weight PEG had a significant effect, which resulted in composites with better shore D hardness and impact strength compared to pure HDPE and composites made with untreated fibers. Furthermore, the use of high molecular weight PEG as a coupling agent resulted in better impact strength and shore D hardness, indicating the presence of a strong interaction between the fibers and the HDPE matrix. Morphological observations of composites made with untreated fibers by scanning electron microscope (SEM) revealed the formation of some fiber aggregation, fiber debonding and fiber pullout in composites made with untreated fibers. Contrary, the composites made with PEG as a treatment and/or coupling agent showed no fiber aggregation or fiber debonding.

Polyethylene glycol alleviates THP-1 cell adhesion to polyurethane, a common biomaterial

Biomaterial rejection has been a topic closely studied due to the development of implants and other medical devices. The goal of biomaterial research is to increase overall biocompatibility which refers to the ability of a biomaterial to work in harmony with surrounding cells. Biomaterial surface properties play an important role in biomaterial rejection which involves the attachment of proteins and cells. Polyethylene glycol (PEG) contains a certain level of hydrophobicity to deter cell adhesion while still maintaining the ability to chemically bind to surfaces. The hypothesis that PEG bound to polyurethane (PU) films can decrease THP-1 cell adhesion was tested. High molecular weight PEG was attached to the surfaces of polyurethane films via an evaporative method in three concentrations (1, 4, and 10%). THP-1 cells were seeded onto polyurethane films, incubated for 2 days, fixed, stained with DAPI, and imaged. An ANOVA with Tukey post-hoc testing showed statistical significance in the number of adhered cells between both 4%, 10% and the control. It was concluded that both 4% and 10% PEG-coated polyurethane films decreased THP-1 adhesion. This preliminary study supports the claim that PEG could be a useful bioinert material to prevent THP-1 macrophage cell adherence, an initial step in the rejection of biomaterials.

Thermally assisted 3D printing of bio-polymer with high solute loading with improved mechanical properties

In this study, a stereolithography process with thermal assistance is presented to address the tradeoff between the flowability and the high concentration of solute loadings at room temperature, by which the improved performance of polymers prepared by stereolithography 3D printing can be achieved. As a demonstration, an easily available polymer of polyethylene glycol diacrylate (PEGDA) with the solute loading of Polyethylene glycol (PEG) was designed for the potential biomedical applications. The maximum soluble concentration of PEG in PEGDA is less than 10 wt% at room temperature while the concentration reaches to 30 % with the temperature of 70 ℃. The comparative experiments proved that the concentration of high molecular weight PEG had a positive effect on the mechanical property of the PEGDA resin. The hardness of the sample printed by the PEGDA resin with PEG by the concentration of 30 wt% is three times higher than that of the PEGDA resin without solute. As the concentration of PEG increases from 15 wt% to 30 wt%, the Young’s modulus has been enhanced from 67.9 MPa to 131.4 MPa while the Young’s modulus for the PEGDA resin without solute is 39.6 MPa. The compression tests with 3D printed lattice structure illustrated that the compressive modulus of the PGEDA resin has been improved by nearly 600 % with the 30 wt% of PEG. The cell proliferation experiments showed that the PEGDA resin with the loading of PEG led to the higher cell activity comparing to the PEGDA resin without solute. The results indicate that the thermally assisted 3D printed PEGDA resin with the high loading of PEG has excellent mechanical properties for the potential biomedical application. This study is expected to demonstrate the thermally assisted stereolithography 3D printing process for the polymer with high solute loading, which contributes to explore the printable materials with improved performance.

MRNA-1273 but not BNT162b2 induces antibodies against polyethylene glycol (PEG) contained in mRNA-based vaccine formulations

Two messenger RNA (mRNA)-based vaccines are widely used globally to prevent coronavirus disease 2019 (COVID-19). Both vaccine formulations contain PEGylated lipids in their composition, in the form of polyethylene glycol [PEG] 2000 dimyristoyl glycerol for mRNA-1273, and 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide for BNT162b2. It is known that some PEGylated drugs and products for human use which contain PEG are capable of eliciting immune responses that lead to to detectable PEG-specific antibodies in serum. In this study, we determined if any of the components of mRNA-1273 or BNT162b2 formulations elicited PEG-specific antibody responses in serum by enzyme linked immunosorbent assay (ELISA). We detected an increase in the reactivity to mRNA vaccine formulations in mRNA-1273 but not BNT162b2 vaccinees’ sera in a prime-boost dependent manner. Furthermore, we observed the same pattern of reactivity against irrelevant lipid nanoparticles from an influenza virus mRNA formulation and found that the reactivity of such antibodies correlated well with antibody levels against high and low molecular weight PEG. Using sera from participants selected based on the vaccine-associated side effects experienced after vaccination, including delayed onset, injection site or severe allergic reactions, we found no obvious association between PEG antibodies and adverse reactions. Overall, our data shows a differential induction of anti-PEG antibodies by mRNA-1273 and BNT162b2. The clinical relevance of PEG reactive antibodies induced by administration of the mRNA-1273 vaccine, and the potential interaction of these antibodies with other PEGylated drugs remains to be explored.

Tolerance of the mRNA COVID-19 vaccines in patients with reported taxane reactions

Tolerance of the mRNA COVID-19 vaccines in patients with reported taxane reactions

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

Safety of COVID-19 vaccination in patients with polyethylene glycol allergy: A case series

A ready-to-use, thermoresponsive, and extended-release delivery system for the paranasal sinuses.

A drug delivery system for the paranasal sinuses consisting of a freeze-dried thermoresponsive hydrogel with degradable microspheres, called FD-TEMPS (Freeze Dried-Thermogel, Extended-release Microsphere-based delivery to the Paranasal Sinuses), was developed. Glass transition temperatures (Tg') of the maximally freeze concentrated solutions consisting of poly(N-isopropylacrylamide) (pNIPAAm) and polyethylene glycol (PEG) were determined by differential scanning calorimetry, which informed optimization of the thermogel formulation. By replacing low molecular weight (MW) PEG (200Da) with a higher MW PEG (2000Da), the resulting freeze-dried gel exhibited a brittle texture, porous structure, and low residual moisture (< 3% measured by thermal gravimetric analysis). When combined with poly(lactic-co-glycolic acid) microspheres (PLGA MSs) and freeze dried, the complete system (FD-TEMPS) exhibited enhanced shelf-stability. Specifically, the smooth, spherical morphology of the MSs and initial release kinetics were maintained following 6weeks of storage under ambient conditions. Furthermore, FD-TEMPS remained in place after application to a simulated mucosal surface, suggesting that it could be more uniformly distributed along the sinonasal mucosa in vivo. Freeze drying enables this delivery system to be stored as a ready-to-use product for better ease of clinical translation without compromising the thermoresponsive or sustained release characteristics that would enable local delivery of therapeutics to the sinonasal mucosa.

Patient with constipation syndrome at the ambulatory-polyclinic reception: actual aspects of differential diagnosis and treatment

Constipation is a serious medical and social problem due to the widespread prevalence of this condition, a decrease in the quality of life and social activity of patients. For the successful treatment of constipation, it is necessary to establish the causes leading to the violation of the stool in the patient. And this task is a priority for the doctor at the outpatient stage.The clinical features of constipation largely depend on their cause, duration, severity and characteristics of intestinal damage. Constipation is often accompanied by general somatic and other gastroenterological symptoms.Within the framework of the review article, the main conditions and diseases are considered, in the clinical picture of which there is constipation syndrome, which must be considered by the doctor at the outpatient stage when conducting differential diagnosis and prescribing appropriate treatment, which also presupposes impact on causal factors. Currently, drugs based on high molecular weight polyethylene glycol 4000 are widely used to treat chronic constipation in adults and children in most countries of the world. Preparations based on polyethylene glycol 4000 are affordable and easy to use, they can be used both on an outpatient basis and in a hospital. Polyethylene glycol 4000 preparations act quickly, are highly effective and well tolerated, have a high safety profile (practically does not affect homeostasis) both for adult patients and in pediatric practice. International clinical trials have shown the possibility of long-term use of polyethylene glycol 4000 preparations.Current international clinical guidelines and domestic clinical guidelines for the treatment of constipation recommend the use of polyethylene glycol 4000 preparations instead of lactulose and volume-forming laxatives in the symptomatic treatment of constipation in children and adults. In the second part of the review, the possibilities of polyethylene glycol 4000 and the first domestic drug polyethylene glycol 4000 in the treatment of chronic constipation are considered.

Tunable temperature-responsive permeable composite films using polyethylene glycol as a phase change material

Poly(ether-block-amide) (PEBAX)/polyethylene glycol (PEG) (PEBAX/PEG) composite films were successfully prepared, via solution casting methods, for use as temperature-responsive permeable composite films. Their morphologies, thermal properties, and permeabilities were investigated as a function of PEG content. The introduction of high molecular weight PEG into PEBAX results in enhancement of thermal stability in the composite films. As the PEG content was increased, water vapor uptake increased, but the vapor diffusion rate decreased because of effects related to chemical affinity and crystallinity. All PEBAX/PEG composite films exhibited a jump in permeability at temperatures near the PEG phase transition temperature, and this depends on PEG content. This indicates that considerable gas passed through the composite films at temperatures near the PEG phase transition temperature, and this can be controlled by introducing different amounts of PEG. Our result can provide the insights into the further development of self-venting materials using temperature-responsive permeable materials for food, agricultural, and biomedical packaging.

Breaking Polymer Chains with Self‐Propelled Light‐Controlled Navigable Hematite Microrobots

AbstractThe increasing use of polymers has led to an uncontrollable accumulation of polymer waste in the environment, evidencing the urgent need for effective and definitive strategies to degrade them. Here, self‐propelled light‐powered magnetic field‐navigable hematite/metal Janus microrobots that can actively move, capture, and degrade polymers are presented. Janus microrobots are fabricated by asymmetrically depositing different metals on hematite microspheres prepared by low‐cost and large‐scale chemical synthesis. All microrobots exhibit fuel‐free motion capability, with light‐controlled on/off switching of motion and magnetic field‐controlled directionality. Higher speeds are observed for bimetallic coatings with respect to single metals. This is due to their larger mixed potential difference with hematite as indicated by Tafel measurements. As a model for polymers, the total degradation of high molecular weight polyethylene glycol is demonstrated by matrix‐assisted laser desorption/ionization mass spectrometry. This result is attributed to the active motion of microrobots, enhanced electrostatic capture of polymer chains, improved charge separation at the hematite/metal interface, and catalyzed photo‐Fenton reaction. This work opens the route toward the degradation of polymers and plastics in water using light.

Tuning the micro-phase separation of the PES-g-PEG comb-like copolymer membrane for efficient CO2 separation

As a common CO2 separation membrane material, polyethylene glycol (PEG) with ether oxygen groups shows high dissolution selectivity to CO2. However, high molecular weight PEG has strong crystallinity, resulting in low gas flux, while the low molecular weight PEG has poor mechanical properties. Block copolymers containing PEG segments can address this challenge but are difficult to synthesize. In this work, a series of polyether sulfone (PES) comb-like copolymer with PEG side chains were prepared by the polycondensation followed by the thiol-ene click chemistry. By manipulating the density and length of PEG side chains (Mn = 550, 1000, 2000) to adjust the fine structure of the micro-phase separation, the gas separation performance of the PES-g-PEG membrane was optimized. The PES-g-PEG polymers have two glass transition temperatures (Tg), which are attributed to the PES main chain and PEG side chains. The Tg-PEG and Tg-PES difference (ΔTg) is highly correlated with the PEG side chain density and can be used to interpret the phase separation degree. The copolymer membrane with shorter PEG side chains achieved higher chain density and more developed micro-phase separation, which was facilitated by thermal annealing. As a result, PES A-g-PEG550 membrane shows the best gas separation performance with the CO2 permeability of 26.8 Barrer and the CO2/N2 selectivity of 27.6. The permeability variation with the microstructure of PES-g-PEG mostly relies on the side chain density rather than volume fraction or side chain molecular weight. We believe this study of the gas separation performance of the comb-like copolymer material is meaningful for the further application of membrane technology in CO2 capture and separation.

Fouling in ocular devices: implications for drug delivery, bioactive surface immobilization, and biomaterial design.

The last 30years has seen a proliferation of research on protein-resistant biomaterials targeted at designing bio-inert surfaces, which are prerequisite for optimal performance of implantable devices that contact biological fluids and tissues. These efforts have only been able to yield minimal results, and hence, the ideal anti-fouling biomaterial has remained elusive. Some studies have yielded biomaterials with a reduced fouling index among which high molecular weight polyethylene glycols have remained dominant. Interestingly, the field of implantable ocular devices has not experienced an outflow of research in this area, possibly due to the assumption that biomaterials tested in other body fluids can be translated for application in the ocular space. Unfortunately, progression in the molecular understanding of many ocular conditions has brought to the fore the need for treatment options that necessitates the use of anti-fouling biomaterials. From the earliest implanted horsehair and silk seton for glaucoma drainage to the recent mini telescopes for sight recovery, this review provides a concise incursion into the gradual evolution of biomaterials for the design of implantable ocular devices as well as approaches used to overcome the challenges with fouling. The implication of fouling for drug delivery, the design of immune-responsive biomaterials, as well as advanced surface immobilization approaches to support the overall performance of implantable ocular devices are also reviewed.

PEGylation of recombinant human deoxyribonuclease I decreases its transport across lung epithelial cells and uptake by macrophages.

Conjugation to high molecular weight (MW ≥ 20 kDa) polyethylene glycol (PEG) was previously shown to largely prolong the lung residence time of recombinant human deoxyribonuclease I (rhDNase) and improve its therapeutic efficacy following pulmonary delivery in mice. In this paper, we investigated the mechanisms promoting the extended lung retention of PEG-rhDNase conjugates using cell culture models and lung biological media. Uptake by alveolar macrophages was also assessed in vivo. Transport experiments showed that PEGylation reduced the uptake and transport of rhDNase across monolayers of Calu-3 cells cultured at an air-liquid interface. PEGylation also decreased the uptake of rhDNase by macrophages in vitro whatever the PEG size as well as in vivo 4h following intratracheal instillation in mice. However, the reverse was observed in vivo at 24h due to the higher availability of PEGylated rhDNase in lung airways at 24 h compared with rhDNase, which is cleared faster. The uptake of rhDNase by macrophages was dependent on energy, time, and concentration and occurred at rates indicative of adsorptive endocytosis. The diffusion of PEGylated rhDNase in porcine tracheal mucus and cystic fibrosis sputa was slower compared with that of rhDNase. Nevertheless, no significant binding of PEGylated rhDNase to both media was observed. In conclusion, decreased transport across lung epithelial cells and uptake by macrophages appear to contribute to the longer retention of PEGylated rhDNase in the lungs.

PEG-containing siloxane materials by metal-free click-chemistry for ocular drug delivery applications

Metal-free click-chemistry can be used to create silicone hydrogels for ocular drug delivery applications, imparting the benefits of silicones without catalyst contamination. Previous work has demonstrated the capacity for these materials to significantly reduce protein adsorption. Building upon this success, the current work examines and optimizes different materials in terms of their protein adsorption and drug release capabilities. Specifically, incorporating lower molecular weight poly-ethylene glycol (PEG) is better able to reduce protein adsorption. However, with higher molecular weight PEG, the materials exhibit excellent water content and better drug release profiles. The lower molecular weight PEG is also able to deliver the drug over a period in excess of four months, with the amount of crosslinking having the greatest impact on the amount of drug release. Overall, these materials show great promise for ocular applications.

Modulating the rheological response of shear thickening fluids by variation in molecular weight of carrier fluid and its correlation with impact resistance of treated p-aramid fabrics

The present study deals with the effect of molecular weight of carrier fluid on the rheological behaviour of shear thickening fluid (STF) and impact energy absorption by treated p-aramid fabrics. High molecular weight polyethylene glycols (HMW-PEG: 1000, 3000 and 6000 g mol−1) were individually added to a mixture of PEG 200 and PEG 600 to prepare ternary mixtures of carrier fluids. Increase in average molecular weight of the carrier fluid via addition of PEG 1000 and PEG 3000 enhanced the dilatant behaviour of STF. On the other hand, addition of PEG 6000 led to a rheological response inferior to that obtained via addition of PEG 3000 owing to solidification of the former at room temperature resulting in fusion of silica particles. However, an inverse relation was observed between the rheological behaviour of HMW-PEG based STFs and impact resistance of p-aramid fabrics treated with them. The diminution in impact energy absorption occurred due to lubrication effect caused by long polymer chains of HMW-PEG. On the other hand, fusion of solidified PEG 6000 and silica particles created rough microstructures over the yarn surface, which enhanced inter-yarn friction, resulting in improved impact energy absorption.