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Molecules (Basel, Switzerland) Apr 2022Aqueous solutions of polyethylene glycol are studied by small-angle neutron scattering over a broad range of polymer molecular masses and concentrations. The scattering...
Aqueous solutions of polyethylene glycol are studied by small-angle neutron scattering over a broad range of polymer molecular masses and concentrations. The scattering data were modeled by a Gaussian chain form factor combined with random phase approximation, which provided good fits over the whole studied concentration range. The results showed that polyethylene glycol in the molecular mass range 0.4-20 kDa in water at physiological temperature T = 37 °C behaves like a random coil in nearly theta solvent conditions. The obtained results serve as a reference for the description of complex mixtures with PEG used in various applications.
Topics: Micelles; Polyethylene Glycols; Polymers; Solutions; Solvents; Water
PubMed: 35458769
DOI: 10.3390/molecules27082573 -
Advanced Science (Weinheim,... Apr 2022Protein therapeutics, except for antibodies, have a short plasma half-life and poor stability in circulation. Covalent coupling of polyethylene glycol (PEG) to protein...
Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.
Protein therapeutics, except for antibodies, have a short plasma half-life and poor stability in circulation. Covalent coupling of polyethylene glycol (PEG) to protein drugs addresses this limitation. However, unlike previously thought, PEG is immunogenic. In addition to induced PEG antibodies, ≈70% of the US population has pre-existing anti-PEG antibodies. Both induced and preexisting anti-PEG antibodies result in accelerated drug clearance, reduced clinical efficacy, and severe hypersensitivity reactions that have limited the clinical utility of uricase, an enzyme drug for treatment for refractory gout that is decorated with a PEG corona. Here, the authors synthesize a poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) conjugate of uricase that decorates the protein with multiple polymer chains to create a corona to solve these problems. The resulting uricase-POEGMA is well-defined, has high bioactivity, and outperforms its PEG counterparts in its pharmacokinetics (PK). Furthermore, the conjugate does not induce anti-POEGMA antibodies and is not recognized by anti-PEG antibodies. These findings suggest that POEGMA conjugation may provide a solution to the immunogenicity and antigenicity limitations of PEG while improving upon its PK benefits. These results transcend uricase and can be applied to other PEGylated therapeutics and the broader class of biologics with suboptimal PK.
Topics: Antibodies; Antigens; Gout; Humans; Immunity; Polyethylene Glycols; Polymers; Urate Oxidase
PubMed: 35133079
DOI: 10.1002/advs.202103672 -
Molecular Pharmaceutics Aug 2018Nanoparticle delivery systems offer advantages over free drugs, in that they increase solubility and biocompatibility. Nanoparticles can deliver a high payload of... (Review)
Review
Nanoparticle delivery systems offer advantages over free drugs, in that they increase solubility and biocompatibility. Nanoparticles can deliver a high payload of therapeutic molecules while limiting off-target side effects. Therefore, delivery of an existing drug with a nanoparticle frequently results in an increased therapeutic index. Whether of synthetic or biologic origin, nanoparticle surface coatings are often required to reduce immune clearance and thereby increase circulation times allowing the carriers to reach their target site. To this end, polyethylene glycol (PEG) has long been used, with several PEGylated products reaching clinical use. Unfortunately, the growing use of PEG in consumer products has led to an increasing prevalence of PEG-specific antibodies in the human population, which in turn has fueled the search for alternative coating strategies. This review highlights alternative bioinspired nanoparticle shielding strategies, which may be more beneficial moving forward than PEG and other synthetic polymer coatings.
Topics: Biomimetic Materials; Chemical Engineering; Chemistry, Pharmaceutical; Click Chemistry; Clinical Trials as Topic; Drug Carriers; Humans; Immune System; Nanoparticles; Polyethylene Glycols
PubMed: 29733602
DOI: 10.1021/acs.molpharmaceut.8b00292 -
Indian Pediatrics Dec 2021
Topics: Colon; Drug Administration Schedule; Humans; Polyethylene Glycols
PubMed: 34939578
DOI: No ID Found -
Biological & Pharmaceutical Bulletin 2014PEGylation changes the physical and chemical properties of the biomedical molecule, such as its conformation, electrostatic binding, and hydrophobicity, and results in... (Review)
Review
PEGylation changes the physical and chemical properties of the biomedical molecule, such as its conformation, electrostatic binding, and hydrophobicity, and results in an improvement in the pharmacokinetic behavior of the drug, while it also causes some disadvantages of which cannot be neglected. The available data manifests that polyethylene glycol (PEG) itself shows potential risk, such as immunogenicity of the PEG and PEG-containing vacuoles in cells observed with PEGylated biologicals. Decreased activity and heterogeneity are also the negative aspects of PEGylation. The unfavorable impacts which are brought by the PEGylation are described here with examples of modified therapeutic proteins on the market and used in the clinical trials.
Topics: Antibody Formation; Humans; Polyethylene Glycols; Proteins; Vacuoles
PubMed: 24334536
DOI: 10.1248/bpb.b13-00661 -
United European Gastroenterology Journal Oct 2020Few head-to-head comparisons of the different classes of laxatives have been conducted. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Few head-to-head comparisons of the different classes of laxatives have been conducted.
OBJECTIVE
The objective of this work is to compare the efficacy of lactulose plus paraffin vs polyethylene glycol in the treatment of functional constipation (non-inferiority study).
METHODS
This randomised, parallel-group, multicentre phase 4 study recruited patients with functional constipation diagnosed according to Rome III criteria. Patients received lactulose plus paraffin or polyethylene glycol for 28 days. The primary end point was the change from baseline in the Patient Assessment of Constipation-Symptoms (PAC-SYM) score.
RESULTS
A total of 363 patients were randomised to lactulose plus paraffin ( = 179) or polyethylene glycol ( = 184). On day 28, the mean PAC-SYM score decreased significantly vs baseline with both treatments ( < 0.001). The lower boundary of the 95% CI exceeded the pre-specified limit of -0.25, therefore establishing non-inferiority of lactulose plus paraffin vs polyethylene glycol. At least one adverse event occurred in 20 patients (11.2%) in the lactulose plus paraffin group and in 26 patients (14.2%) in the polyethylene glycol group, most of which were of mild or moderate severity and unrelated to study drugs.
CONCLUSION
Lactulose plus paraffin may be used interchangeably with polyethylene glycol for the pharmacological treatment of functional constipation. EudraCT number 2015-003021-34.
Topics: Administration, Oral; Adult; Aged; Constipation; Drug Combinations; Female; Humans; Lactulose; Laxatives; Male; Middle Aged; Paraffin; Polyethylene Glycols; Quality of Life; Severity of Illness Index; Treatment Outcome
PubMed: 32594884
DOI: 10.1177/2050640620937913 -
Biomedicine & Pharmacotherapy =... Aug 2022Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study...
BACKGROUND
Traditionally, vasopressors and crystalloids have been used to stabilize brain dead donors; however, the use of crystalloid is fraught with complications. This study aimed to investigate the effectiveness of a newly developed impermeant solution, polyethylene glycol-20k IV solution (PEG-20k) for resuscitation and support of brain dead organ donors.
METHODS
Brain death was induced in adult beagle dogs and a set volume of PEG-20k or crystalloid solution was given thereafter. The animals were then resuscitated over 16 h with vasopressors and crystalloid as necessary to maintain mean arterial pressure of 80-100 mmHg. The kidneys were procured and cold-stored for 24 h, after which they were analyzed using the isolated perfused kidney model.
RESULTS
The study group required significantly less crystalloid volume and vasopressors while having less urine output and requiring less potassium supplementation than the control group. Though the two groups' mean arterial pressure and lactate levels were comparable, the study group's kidneys showed less preservation injury after short-term reperfusion indexed by decreased lactate dehydrogenase release and higher creatinine clearance than the control group.
CONCLUSIONS
The use of polyethylene glycol-20k IV solution for resuscitating brain dead donors decreases cell swelling and improves intravascular volume, thereby improving end organ oxygen delivery before procurement and so preventing ischemia-reperfusion injury after transplantation.
Topics: Animals; Brain Death; Crystalloid Solutions; Disease Models, Animal; Dogs; Humans; Polyethylene Glycols; Tissue Donors
PubMed: 35714513
DOI: 10.1016/j.biopha.2022.113293 -
Annals of Palliative Medicine Nov 2020Constipation is a common gastrointestinal complication during pregnancy. The prevalence of constipation is higher in pregnant women compared to the general population... (Randomized Controlled Trial)
Randomized Controlled Trial
A comparison of the safety and efficacy of polyethylene glycol 4000 and lactulose for the treatment of constipation in pregnant women: a randomized controlled clinical study.
BACKGROUND
Constipation is a common gastrointestinal complication during pregnancy. The prevalence of constipation is higher in pregnant women compared to the general population owing to the physiological changes that occur throughout pregnancy. Lactulose and polyethylene glycol belong to a class of medications known as osmotic laxatives. The purpose of this study is to compare the safety and efficacy of polyethylene glycol and lactulose in pregnant women with constipation.
METHODS
In this study, we selected 113 pregnant women with constipation who attended the Department of Gastroenterology, Affiliated Hospital of Jiangnan University from May 1, 2017 to April 30, 2020. The included patients were randomly divided into two groups. The observation group used polyethylene glycol 4000 (manufactured by Beau four Ipsen Industry, France, National Medicine Standard: H20130145), 10 g, twice daily. The control group used lactulose (manufactured by Abbott Biologicals BV, Netherlands, National Medicine Standard: H20120387) 15 mL, twice daily. Both groups were given a 3-week course of treatment, and were observed for any adverse drug reactions. The clinical effects were compared every week during the 3-week treatment.
RESULTS
Treatment was found to be effective in both the observation and control groups, as measured by a significant difference in the Wexner constipation scores of patients before and after treatment (P<0.05). Although no significant differences in the final effect of treatment were observed between the two groups (P>0.05), analysis of the Wexner scores at the first and second week of treatment indicated that polyethylene glycol had a faster therapeutic effect than lactulose (P=0.06, P=0.029).
CONCLUSIONS
Compared with lactulose, Polyethylene glycol 4000 can significantly shorten the treatment course for constipation during pregnancy.
Topics: Constipation; Female; France; Humans; Lactulose; Polyethylene Glycols; Pregnancy; Pregnant Women; Treatment Outcome
PubMed: 33302648
DOI: 10.21037/apm-20-1674 -
American Journal of Physiology. Lung... Apr 2021Extracellular vesicles (EVs) in bodily fluids play an essential role in cell-cell cross talk and potentially serve as novel biomarkers in "liquid biopsy." It is crucial...
Extracellular vesicles (EVs) in bodily fluids play an essential role in cell-cell cross talk and potentially serve as novel biomarkers in "liquid biopsy." It is crucial to have a consistent, efficient, and reliable method to separate EVs from bodily fluids. Currently, there is no universally accepted, "best" method to separate EVs. Besides differential ultracentrifugation (UC), polyethylene glycol (PEG) is among the commonly used methods for EV separation from bodily fluids. However, the optimal concentration of PEG to be used remains inadequately addressed. We initially observed that the concentration of PEG has a significant impact on the amount of separated EVs and EV-cargos, which are recovered from bronchoalveolar lavage fluid (BALF). To determine the optimal PEG concentration to be used in EV separation from BALF, we first separated the BALF and serum from wild-type C57BL/6 mice. Next, various concentrations of PEG (5%, 10%, and 15% PEG), a commercial kit, and UC were used to obtain EVs from BALF and serum. EVs were characterized, and EV-cargo protein, RNA, and miRNA levels were determined. We found that high concentration of PEG (10% and 15%) altered various EV parameters that are frequently used in EV studies, including EV yield, purity, and morphology. Using miR-15a, miR-142, and miR-223 as examples, we found that 10% and 15% PEG robustly reduced the detected levels of EV-cargo miRNAs compared with those in the EVs separated using UC or 5% PEG. Collectively, low concentration of PEG facilitates the optimal BALF EV separation.
Topics: Animals; Biomarkers; Bronchoalveolar Lavage Fluid; Cell Separation; Extracellular Vesicles; Mice; Mice, Inbred C57BL; Polyethylene Glycols
PubMed: 33438468
DOI: 10.1152/ajplung.00318.2020 -
Biomolecules Feb 2020The development of anti-icing, anti-frosting transparent plates is important for many reasons, such as poor visibility through the ice-covered windshields of vehicles....
The development of anti-icing, anti-frosting transparent plates is important for many reasons, such as poor visibility through the ice-covered windshields of vehicles. We have fabricated new glass surfaces coated with polypeptides which mimic a part of winter flounder antifreeze protein. We adopted glutaraldehyde and polyethylene glycol as linkers between these polypeptides and silane coupling agents applied to the glass surfaces. We have measured the contact angle, the temperature of water droplets on the cooling surfaces, and the frost weight. In addition, we have conducted surface roughness observation and surface elemental analysis. It was found that peaks in the height profile, obtained with the atomic force microscope for the polypeptide-coated surface with polyethylene glycol, were much higher than those for the surface without the polypeptide. This shows the adhesion of many polypeptide aggregates to the polyethylene glycol locally. The average supercooling temperature of the droplet for the polypeptide-coated surface with the polyethylene glycol was lower than for the polypeptide-coated surface with glutaraldehyde and the polyethylene-glycol-coated surface without the polypeptide. In addition, the average weight of frost cover on the specimen was lowest for the polypeptide-coated surface with the polyethylene glycol. These results argue for the effects of combined polyethylene glycol and polypeptide aggregates on the locations of ice nuclei and condensation droplets. Thus, this polypeptide-coating with the polyethylene glycol is a potential contender to improve the anti-icing and anti-frosting of glasses.
Topics: Antifreeze Proteins; Freezing; Glass; Ice; Microscopy, Atomic Force; Peptides; Polyethylene Glycols; Surface Properties; Temperature; Water
PubMed: 32050479
DOI: 10.3390/biom10020259