Meta-Analysis Review

Authors: Miguel Mínguez, Antonio López Higueras, Javier Júdez...

OBJECTIVE

The objective of this study was to evaluate in an analytical and descriptive manner the evidence published so far on the use of polyethylene glycol (PEG), with or without electrolytes, in the management of functional constipation and the treatment of fecal impaction.

METHODOLOGY

Search on MEDLINE, EMBASE and Cochrane databases until May 2016 of all publications adjusted to the following terms: constipation AND/OR fecal impaction AND (PEG OR polyethylene glycol OR macrogol OR movicol OR idralax OR miralax OR transipeg OR forlax OR golytely OR isocolan OR mulytely) NOT colonoscopy. Critical reading of selected articles (English or Spanish), sorting their description according to group age (adult/pediatric age) and within those, in accordance with study features (efficacy evaluation versus placebo, doses query, safety, comparison with other laxatives, observational studies and monographic review articles of polyethylene glycol or meta-analysis).

RESULTS

Fifty-eight publications have been chosen for descriptive analysis; of them, 41 are clinical trials, eight are observational studies and nine are systematic reviews or meta-analysis. Twelve clinical trials evaluate PEG efficacy versus placebo, eight versus lactulose, six are dose studies, five compare polyethylene glycol with and without electrolytes, two compare its efficacy with respect to milk of magnesia, and the rest of the trials evaluate polyethylene glycol with enemas (two), psyllium (one), tegaserod (one), prucalopride (one), paraffin oil (one), fiber combinations (one) and Descurainia sophia (one).

CONCLUSIONS

Polyethylene glycol with or without electrolytes is more efficacious than placebo for the treatment of functional constipation, either in adults or in pediatric patients, with great safety and tolerability. These preparations constitute the most efficacious osmotic laxatives (more than lactulose) and are the first-line treatment for functional constipation in the short and long-term. They are as efficacious as enemas in fecal impaction, avoid the need for hospital admission and are well tolerated by patients (mainly when administered without electrolytes).

Topics: Adult; Child; Constipation; Fecal Impaction; Humans; Laxatives; Polyethylene Glycols

PubMed: 27871178
DOI: 10.17235/reed.2016.4571/2016

Authors: Nerea Guembe-Michel, Adrián Durán, Rafael Sirera...

Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as "molecular necklaces". While the synthesis and reaction mechanisms of these structures in solution have been widely described, their solvent-free production has received little attention, despite the advantages that this route may offer. We propose in this work a kinetic mechanism that describes the PPR formation in the solid phase as a process occurring in two consecutive stages. This mechanism has been used to investigate the spontaneous formation of a PPR that occurs when grinding α-Cyclodextrin (α-CD) with polyethylene glycol (PEG). In the threading stage, the inclusion of the polymer and subsequent release of the water molecules lodged in the cavity of the macrocycle cause vibrational changes that are reflected in the time-dependence of the FTIR-ATR spectra, while the further assembly of PPRs to form crystals produces characteristic reflections in the XRD patterns, due to the channel-like arrangement of CDs, that can be used to track the formation of the adduct in crystalline form. The effects that working variables have on the kinetics of the reaction, such as temperature, feed ratio, molar mass of the polymer and the introduction of an amorphous block in the polymer structure, have been investigated. The rate constants of the threading step increase with the temperature and the activation energy of the process increases at lower proportions of CD to PEG. This is attributed to the lower degree of covering of the polymer chain with CDs that reduces the hydrogen-bonding driven stabilization between adjacent macrocycles. The formation of crystalline PPR, which takes place slowly at room temperature, is markedly promoted at higher temperatures, with lower proportions of CD favoring both the formation and the growth of the crystals. The molar mass of the polymer does not modify the typical channel-like arrangement of packed PPRs but the conversion into crystalline PPR diminishes when using PEG1000 instead of PEG400. At a microscopic level, the crystals arrange into lamellar structures, in the order of hundreds of nm, embedded in an amorphous-like matrix. The introduction of a polypropylene oxide block in the structure of the polymer (Pluronic L62) renders poorer yields and a considerable loss of crystallinity of the product of the reaction. The methodology here proposed can be applied to the general case of inclusion complexes of CDs with drugs in the solid phase, or to multicomponent systems that contain polymers as excipients in pharmaceutical formulations along with CDs.

Topics: Crystallization; Cyclodextrins; Kinetics; Poloxamer; Polyethylene Glycols; Rotaxanes; Solvents; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; alpha-Cyclodextrins

PubMed: 35054867
DOI: 10.3390/ijms23020685

Authors: Zahoor Ahmad Parray, Faizan Ahmad, Mohamed F Alajmi...

One of the significant proteins that have attracted research groups due to virtue of being a potent selective anticancer drug target and property of triggering apoptosis upon release in cytoplasm is cytochrome c (cyt c). The mechanical transformations due to the macromolecular crowding in membrane in the mammalian cell are proposed to be useful inductors of changes in volume. It is very interesting to know that mitochondrial function were observed to be improved by polyethylene glycol (PEG) interaction, which in turn inhibits the cyt c (a pro-apoptotic cell death factor). In this work, the effect of polyethylene glycol of molecular weight 4 kilo Dalton (PEG 4 kDa) was investigated to highlight the structural transformations (tertiary and secondary structure) in cyt c using a choice of spectroscopic techniques (including UV-Vis absorption, near-UV, far-UV and Soret circular dichroism and fluorescence spectroscopy), which shows noteworthy shifts in the secondary and tertiary structures at higher concentrations of PEG 4 kDa with small changes in the heme-globular interactions. The size distribution changes of native protein treated with various concentrations of the crowder were observed and analyzed by dynamic light scattering (DLS). The interaction studies of the crowder with the protein was observed and analyzed by FTIR, isothermal titration calorimetry, time resolved fluorescence and molecular docking. The investigations suggested that the structural changes in the protein occurred due to soft interactions of PEG 4 kDa, which usually destabilizes proteins. The experimental evidence in this study proposed that crowding could be another approach to mechanical super-competition and free of certain markers that could aid in the identification and control of various diseases. This study suggests that crowders at specific concentrations, which softly interact with proteins, can be exploited as remedy for various diseases.

Topics: Animals; Cytochromes c; Horses; Molecular Docking Simulation; Polyethylene Glycols; Protein Conformation; Protein Stability

PubMed: 33742055
DOI: 10.1038/s41598-021-85792-4

Comparative Study Meta-Analysis Review

Authors: Peter Katelaris, Vasi Naganathan, Ken Liu...

BACKGROUND

Polyethylene glycol is commonly used to manage constipation and is available with or without electrolytes. The addition of electrolytes dates back to its initial development as lavage solutions in preparation for gastrointestinal interventions. The clinical utility of the addition of electrolytes to polyethylene glycol for the management of constipation is not established. The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of functional constipation in adults.

METHODS

A systematic review was conducted to identify randomised controlled clinical trials that assessed the use of polyethylene glycol in functional constipation. The primary outcome was the mean number of bowel movements per week.

RESULTS

Nineteen studies were included in the NMA (PEG N = 9, PEG + E N = 8, PEG versus PEG + E N = 2; involving 2247 patients). PEG and PEG + E are both effective, increasing the number of bowel movements per week by 1.8 (95 % Crl 1.0, 2.8) and 1.9 (95 % Crl 0.9, 3.0) respectively versus placebo and by 1.8 (95 % Crl 0.0, 3.5) and 1.9 (95 % Crl 0.2, 3.6) respectively versus lactulose. There was no efficacy difference between PEG + E and PEG (0.1, 95 % Crl -1.1, 1.2) and there were no differences in safety or tolerability.

CONCLUSIONS

Polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. The addition of electrolytes to polyethylene glycol does not appear to offer any clinical benefits over polyethylene glycol alone in the management of constipation.

Topics: Constipation; Electrolytes; Humans; Polyethylene Glycols; Surface-Active Agents; Treatment Outcome

PubMed: 27029340
DOI: 10.1186/s12876-016-0457-9

Randomized Controlled Trial

Authors: Jawad Abou Zeid, Souheil Hallit, Bassem Akiki...

BACKGROUND

Different split regimens of polyethylene glycol are routinely used and no guidelines are available to select an optimal protocol of ingestion. This study aims to compare the efficacy and side effect profile of two different regimens of polyethylene glycol bowel preparation solution: PEG (3 + 1) vs. PEG (2 + 2).

METHODS

240 patients above the age of 18 years were included in the study between June 1st and November 31 2023. Patients were randomly assigned either to Group A, consisting of 115 patients receiving a 3 L of PEG the night before the colonoscopy, and 1 L the same morning of the procedure. Or to group B, where 125 patients ingested 2 L the night before the procedure, and the remaining 2 L the same morning. The cleansing efficacy was evaluated by the attending endoscopist using the Boston Bowel Preparation Scale, through a score assigned for each segment of the colon (0-3). Side effects, tolerability, and willingness to retake the same preparation were listed by an independent investigator using a questionnaire administered before the procedure.

RESULTS

A higher percentage of patients had gastric fullness with the 3 + 1 vs. 2 + 2 preparation (58.3% vs. 31.2%; p <.001). A higher Boston bowel preparation score was seen in patients who took the 2 + 2 vs. 3 + 1 preparation (7.87 vs. 7.23). Using the 2 + 2 preparation was significantly associated with higher Boston bowel preparation scores vs. the 3 + 1 preparation (OR = 1.37, p =.001, 95% CI 1.14, 1.64). After adjustment over other variables (age, gender, comorbidities, previous abdominal surgeries, presence of adenoma, and time between last dose and colonoscopy), results remained the same (aOR = 1.34, p =.003, 95% CI 1.10, 1.62).

CONCLUSION

While both (2 + 2) and (3 + 1) regimens of polyethylene glycol are a good choice for a successful colonoscopy, we recommend the use of (2 + 2) regimen for its superior efficacy in bowel cleansing.

Topics: Humans; Adolescent; Prospective Studies; Colonoscopy; Clinical Protocols; Polyethylene Glycols; Stomach

PubMed: 38609900
DOI: 10.1186/s12876-024-03212-z

Authors: Maurits G L Olthof, Marianna A Tryfonidou, Xifeng Liu...

Off-the-shelf availability in large quantities, drug delivery functionality, and modifiable chemistry and mechanical properties make synthetic polymers highly suitable candidates for bone grafting. However, most synthetic polymers lack the ability to support cell attachment, proliferation, migration, and differentiation, and ultimately tissue formation. Incorporating anionic peptides into the polymer that mimics acidic proteins, which contribute to biomineralization and cellular attachment, could enhance bone formation. Therefore, this study investigates the effect of a phosphate functional group on osteoconductivity and BMP-2-induced bone formation in an injectable and biodegradable oligo[(polyethylene glycol) fumarate] (OPF) hydrogel. Three types of OPF hydrogels were fabricated using 0%, 20%, or 40% Bis(2-(methacryloyloxy)ethyl) phosphate creating unmodified OPF-noBP and phosphate-modified OPF-BP20 and OPF-BP40, respectively. To account for the osteoinductive effect of various BMP-2 release profiles, two different release profiles (i.e., different ratios of burst and sustained release) were obtained by varying the BMP-2 loading method. To investigate the osteoconductive effect of phosphate modification, unloaded OPF composites were assessed for bone formation in a bone defect model after 3, 6, and 9 weeks. To determine the effect of the hydrogel phosphate modification on BMP-2-induced bone formation, BMP-2 loaded OPF composites with differential BMP-2 release were analyzed after 9 weeks of subcutaneous implantation in rats. The phosphate-modified OPF hydrogels (OPF-BP20 and OPF-BP40) generated significantly more bone in an orthotopic defect compared to the unmodified hydrogel (OPF-noBP). Furthermore, the phosphate functionalized surface-enhanced BMP-2-induced ectopic bone formation regardless of the BMP-2 release profile. In conclusion, this study clearly shows that phosphate functional groups improve the osteoconductive properties of OPF and enhanced BMP-2-induced bone formation. Therefore, functionalizing hydrogels with phosphate groups by crosslinking monomers into the hydrogel matrix could provide a valuable method for improving polymer characteristics and holds great promise for bone tissue engineering.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Regeneration; Microscopy, Electron, Scanning; Microspheres; Osteogenesis; Phosphates; Polyethylene Glycols; Rats

PubMed: 29065776
DOI: 10.1089/ten.TEA.2017.0229

Authors: László Almásy, Oleksandr P Artykulnyi, Viktor I Petrenko...

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

Authors: Hafida Zerigui, Radia Labied, Redouane Chebout...

BACKGROUND

Antioxidant polyphenols like gallic acid (GA) and its esters called "gallates", which have health advantages for humans, have grown in significance in maintaining a healthy lifestyle and eating a significant amount of secondary plant phytochemicals. Here, for the first time, we suggest a green synthesis of a brand-new, all-natural diester based on gallic acid and polyethylene glycol.

METHODS

This di-gallate is created in a single step without the use of a solvent (solid-solid reaction). This reaction has a potential yield of up to 90%. The bathochromic shift of the absorption bands from 277 nm to 295 nm in the UV-VIS spectra was caused by the addition of PEG to gallic acid. To confirm the structure of this di-gallate; Fourier-transform infrared (FTIR) spectroscopy, proton and carbon nuclear magnetic resonance ( H and C NMR), the thermal stability identified by thermogravimetric analysis (TGA), X-ray diffraction (XRD), and scanning electron microscopy (SEM) were all used to thoroughly analyze the manufactured product.

RESULTS AND CONCLUSIONS

The acquired results, when compared to the literature spectrums, supported the establishment of the di-ester structure and created new opportunities for a large number of applications.

Topics: Gallic Acid; Polyethylene Glycols; Green Chemistry Technology; Esters; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction

PubMed: 39296352
DOI: 10.12688/f1000research.139861.1

Authors: Simona Serrati, Chiara Martinelli, Antonio Palazzo...

Reproducibility of results is essential for a well-designed and conducted experiment. Several reasons may originate failure in reproducing data, such as selective reporting, low statistical power, or poor analysis. In this study, we used PEG6000 samples from different distributors and tested their capability inducing spheroid formation upon surface coating. MALDI-MS, NMR, FTIR, and Triple SEC analysis of the different PEG60000s showed nearly identical physicochemical properties different, with only minor differences in mass and hydrodynamic radius, and AFM analysis showed no significant differences in the surface coatings obtained with the available PEG6000s. Despite these similarities, just one showed a highly reproducible formation of spheroids with different cell lines, such as HT-29, HeLa, Caco2, and PANC-1. Using the peculiar PEG6000 sample and a reference PEG6000 chosen amongst the others as control, we tested the effect of the cell/PEG interaction by incubating cells in the PEG solution prior to cell plating. These experiments indicate that the spheroid formation is due to direct interaction of the polymer with the cells rather than by interaction of cells with the coated surfaces. The experiments point out that for biological entities, such as cells or tissues, even very small differences in impurities or minimal variations in the starting product can have a very strong impact on the reproducibility of data.

Topics: Caco-2 Cells; Calorimetry, Differential Scanning; Cell Culture Techniques; Chromatography, Gel; HT29 Cells; HeLa Cells; Humans; Magnetic Resonance Spectroscopy; Microscopy, Atomic Force; Polyethylene Glycols; Reproducibility of Results; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy, Fourier Transform Infrared; Spheroids, Cellular; Surface Properties

PubMed: 32191706
DOI: 10.1371/journal.pone.0224002

Authors: Maria Czarnobilska, Małgorzata Bulanda, Magdalena Kurnik-Łucka...

The need for mass population vaccination against Covid-19 poses a public health problem. Allergic symptoms occurring after the 1st dose of the vaccine may result in resignation from the administration of the 2nd dose. However, the majority of patients with mild and/or non-immediate symptoms may be safely vaccinated. The only absolute contraindication to administration of the vaccine is an anaphylactic reaction to any of its ingredients. Polyethylene glycol (PEG), widely used as an excipient in various vaccines, is considered the primary cause of allergic reactions associated with administration of Comirnaty (Pfizer/BioNTech) and Covid-19 Vaccine (Moderna) vaccines. However, hypersensitivity to PEG reported to date seems very rare, considering its widespread use in multiple everyday products, including medicines and cosmetics. In the paper, current literature data describing mechanisms of hypersensitivity reactions to PEG, their clinical symptoms and diagnostic capabilities are presented. Undoubtedly, the issue of hypersensitivity to PEG warrants further research, while patients with the diagnosis require individual diagnostic and therapeutic approach.

Topics: Anaphylaxis; COVID-19; COVID-19 Vaccines; Humans; Hypersensitivity; Polyethylene Glycols; SARS-CoV-2

PubMed: 35180202
DOI: 10.24425/fmc.2021.140004