Polyethylene Glycol Polymers Research Articles

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Insights from Pivotal and Extension Studies.

The development of enhanced half-life recombinant factor VIII (EHL-rFVIII) concentrates has improved the management of hemophilia. Furthermore, the chance of maintaining higher trough levels has allowed higher protection from bleeding and, in turn, improved safely performance for certain types of physical activity. The first technology used to improve the pharmacokinetic profile of factor VIII (FVIII) was fusion with the Fc domain of immunoglobulin G. More recently, conjugation to hydrophilic polymers of polyethylene glycol (PEG) has been demonstrated to prolong plasma half-life of FVIII by means of a reduction in clearance of the molecule due to steric hindrance by PEG covering the protein. Here we report results of a systematic review of pivotal studies on EHL-rFVIII concentrates. Significant heterogeneity is observed among different studies on EHL-rFVIII concentrates, and direct comparisons should be avoided. The annualized bleeding rate has ranged between 1.2 and 1.9 in different EHL-rFVIII concentrates, with a progressive further decrease during extension phases of pivotal studies. Zero bleeding was reported by 40 to 45% of patients. Overall, the emerging treatment options seem to be highly effective and safe, associated with a decreased dosing interval to twice weekly or less, which reduces, but does not entirely eliminate, the burden of treatment. Overall, further information is needed from real-life settings to permit differentiation between EHL-FVIII concentrates and for individualizing treatment.

Covalently Immobilized Battacin Lipopeptide Gels with Activity against Bacterial Biofilms.

Novel antibiotic treatments are in increasing demand to tackle life-threatening infections from bacterial pathogens. In this study, we report the use of a potent battacin lipopeptide as an antimicrobial gel to inhibit planktonic and mature biofilms of S. aureus and P. aeruginosa. The antimicrobial gels were made by covalently linking the N-terminal cysteine containing lipopeptide (GZ3.163) onto the polyethylene glycol polymer matrix and initiating gelation using thiol-ene click chemistry. The gels were prepared both in methanol and in water and were characterised using rheology, Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). Antibacterial and antibiofilm analyses revealed that the gels prepared in methanol have better antibacterial and antibiofilm activity. Additionally, a minimum peptide content of 0.5 wt% (relative to polymer content) is required to successfully inhibit the planktonic bacterial growth and disperse mature biofilms of P. aeruginosa and S. aureus. The antibacterial activity of these lipopeptide gels is mediated by a contact kill mechanism of action. The gels are non-haemolytic against mouse red blood cells and are non-cytotoxic against human dermal fibroblasts. Findings from this study show that battacin lipopeptide gels have the potential to be developed as novel topical antibacterial agents to combat skin infections, particularly caused by S. aureus.

A new strategy for the preparation of core-shell MOF/Polymer composite material as the mixed-mode stationary phase for hydrophilic interaction/ reversed-phase chromatography

A facile method for efficient synthesis of core-shell composite material was proposed. In this method, the silica microspheres were co-modified with metal organic framework (MOF-235) and polyethylene glycol polymer (PEG) and used as mixed-mode stationary phase (MOF-235@PEG@silica) for high-performance liquid chromatography. Elemental analysis, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and Brunauer-Emmett-Teller etc. methods were used to investigate the properties of the core-shell composite material. The MOF-235@PEG@silica stationary phase showed flexible selectivity for the separation of both hydrophilic and hydrophobic compounds especially for the separation of nine alkaloids, which showed superior hydrophilic separation performance than previous MOF-based composite stationary phases. Some factors including the pH of buffer salt, the ratio of organic phase and water phase in the mobile phase have been investigated, suggesting that the chromatographic retention mechanism of the column was a mixed mode of hydrophilic and reversed phase. The composite material also showed excellent chromatographic repeatability with the RSDs of the retention time found to be 0.2%–0.6% (n = 10) and the standard addition test in the actual sample proved that it can be used for practical sample analysis. In short, it provided a general way for preparing MOFs-based composites as mixed-mode chromatographic stationary phases, and changed the current status of MOF-based composite materials as single mode chromatographic stationary phases.

Novel Solid Dispersions of Naphthoquinone Using Different Polymers for Improvement of Antichagasic Activity

IVS320 (3a,10b-dihydro-1H-cyclopenta[b]naphtho[2,3-d]furan-5,10-dione) is a naphthoquinone that has low solubility in aqueous medium, a physical behavior that limits its biological activities, considering that compounds from this class have several activities. In this work, solid dispersions (SDs) prepared between IVS320 and polymers hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG), and polyvinylpyrrolidone (PVP) were developed using physical mixture (PM), kneading (KN), and rotary evaporation (RE) methods. Dispersions were investigated using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetry (TG), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). In addition, in vitro antiparasitic activity in Trypanosoma cruzi Y strains was evaluated. Physical-chemical characterization demonstrated the formation of SDs through the interaction of IVS320 with polymeric matrices. SDs of IVS320-polymer presented a significant potentiation of antichagasic activity, with inhibitory growth around 62% (IVS320-HPMC/RE), 55% (IVS320-PEG/RE), and 85% (IVS320-PVP/RE), while pure IVS320 showed a value of 48% for the highest concentrations evaluated (50 µg/mL).

Natural Antibiotic Oregano in Hydroxyapatite-Coated Titanium Reduces Osteoclastic Bone Resorption for Orthopedic and Dental Applications.

Traditional infection prevention and treatment methods include synthetic antibiotics, which can cause severe adverse side effects. Carvacrol and thymol are biologically active monoterpenoid extractants from oregano leaves with antibiotic capabilities; however, little is known regarding their effects on bone tissue engineering. The objective of this work is to understand their effects on osteogenesis, specifically with osteoblast and osteoclast cells, from surface-modified Ti6Al4V with plasma sprayed hydroxyapatite (HA) coatings. This system is an alternative to cemented implants to aid in bone healing. Results reveal that full carvacrol release from the HA matrix is successful in aqueous environments and modulation of release kinetics can also be made using polycaprolactone (PCL) and polyethylene glycol (PEG) polymers. From HA-pressed disc samples in physiological pH, full carvacrol release is achieved in 10 days using PCL/PEG, about 95% release in 50 days using no polymer, and 60% in 50 days when using a PCL coating. Without polymer, full carvacrol release is achieved after 3 days from HA coatings in both physiological pH and acidic pH, mimicking the post-surgery environment. The release is assessed as a diffusion-based mechanism in phosphate-buffered saline but degradation-based mechanism in acetate buffer solution. Carvacrol and thymol show bacterial inhibition of Staphylococcus epidermidis and no cytotoxic effects on osteoblast proliferation in vitro. Carvacrol and thymol also induce a significant 7% reduction in osteoclast tartrate-resistant acid phosphatase (TRAP) activity, caused by poorly attached cellular morphologies, leading to an approximately 65% reduction in osteoclast resorption pit formation. Our goal is to demonstrate a natural medicinal system that can support bone healing while providing infection prevention and reducing costly revision surgeries for orthopedic and dental applications.

Chemical Tuning of Fibers Drawn from Extensible Hyaluronic Acid Networks.

Polymer fibers with specific chemical and mechanical properties are key components of many biomaterials used for regenerative medicine and drug delivery. Here, we develop a bioinspired, low-energy process to produce mechanically tunable biopolymer fibers drawn from aqueous solutions. Hyaluronic acid (HA) forms dynamic cross-links with branched polyethylene glycol polymers end-functionalized with boronic acids of varied structure to produce extensible polymer networks. This dynamic fiber precursor (DFP) is directly drawn by pultrusion into HA fibers that display high aspect ratios, ranging from 4 to 20 μm in diameter and up to ∼10 m in length. Dynamic rheology measurements of the DFP and tensile testing of the resulting fibers reveal design considerations to tune the propensity for fiber formation and fiber mechanical properties, including the effect of polymer structure and concentration on elastic modulus, tensile strength, and ultimate strain. The materials' humidity-responsive contractile behavior, a unique property of spider silks rarely observed in synthetic materials, highlights possibilities for further biomimetic and stimulus-responsive fiber applications. This work demonstrates that chemical modification of dynamic interactions can be used to tune the mechanical properties of pultrusion-based fibers and their precursors.

Experimental study on improving the strength of concrete by using self-curing technic with Poly ethylene glycol and super absorbent polymer

Increase in infrastructural projects demands the need for workable concrete in the 21st century. With the technological advancement there is a need for looking into an alternate solution to the current day problems in the construction sector. Shortage of water is also a concern in some of the places which demands for the utilization of a better substitute to water in concrete. Internal curing agents like Polyethylene Glycol (PEG400), ceramic and Super Absorbent Polymer are used extensively which would be beneficial for engineering and construction applications. Day by day increasing of waste from disposable diapers will give increase the waste generation and requires large space dumping. To overcome this diapers which are primarily worn by infants, and by children who are not yet potty trained or who experience bedwetting are used in the present study as a self-curing agent along with PEG 400. In this present study, influence of PEG and diaper polymer on the workability and compressive strength of the concrete was investigated. M40 grade of concrete has been adopted for the entire study. Compressive strength at 3, 7, 28 and 90 days was calculated for 150mm X 150mm X150mm cubes with the 1%PEG as a control mix and 1% PEG + varying ratios of 1% to 10% of diaper polymer with 5% interval. It was observed that workability increased with the addition of diaper polymer and the strength decreased.

An injectable hydrogel based on phenylboronic acid hyperbranched macromer encapsulating gold nanorods and Astragaloside IV nanodrug for myocardial infarction

Cardiac tissue engineering has a great applicable prospect in the treatment of heart disease. The hyperbranched polymer polyethylene glycol diacrylate/4-vinyl phenylboronic acid (PEGDA-PBA) and thiol hyaluronic acid (HA-SH) form an in situ hydrogel that adsorbs AST NPs to achieve drug targeting and sustained release. In addition, the composite hydrogel has certain properties of electrical stimulation through doping of gold nanorods (GNRs). In vitro studies indicated that this gel system exhibited electrical conductivity similar as a natural heart, and has a good efficacy to release drug. Our present study found that the injectable conductive hydrogel loaded with Astragaloside IV nanoparticles (AST NPs) effectively inhibited left ventricular remodeling and myocardial dysfunction after myocardial infarction (MI) in rats. HB (PEG-PBA)/HA-SH/AST NPs/GNRs also upregulated infarct margin angiogenesis, reduced cell apoptosis, and increased an expression of Connexm43 (Cx43). Thus, this bioactive injectable conductive hydrogel may provide an effective therapeutic strategy for the treatment of MI.

Effect of coating excipients on chemical stability of active coated tablets

The objective of this study was to understand the impact of coating excipients on the chemical stability of active pan coated peliglitazar, which was prone to acid as well as base-catalyzed degradation. Four different coating formulations containing either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) as a coating polymer and triacetin (glycerol triacetate) or polyethylene glycol (PEG) as a plasticizer/detackifier were used for coating of peliglitazar in a perforated pan coater. Tablets of one-milligram strength were manufactured by suspending the drug in the coating suspension and spray coating onto inert core tablets. The active coated tablets were placed on stability (40 °C/75% RH) in high-density polyethylene (HDPE) bottles in closed condition with desiccants or in open condition. Tablet samples were withdrawn and analyzed for degradants using a stability-indicating HPLC method. The overall stability for the film-forming polymer-plasticizer/detackifier combination showed the rank order: HPMC-triacetin > PVA-triacetin > HPMC-PEG > PVA-PEG. Higher stability of triacetin systems over PEG systems was attributed to lower solubility of peliglitazar in triacetin coating systems. For the same plasticizer/detackifier, higher stability of HPMC over PVA-based formulations was attributed to lower solubility and mobility of peliglitazar in HPMC compared with the PVA-based coating.

The effect of bovine serum albumin-glutaraldehyde and polyethylene glycol polymer on neointimal hyperplasia in rabbit carotid artery anastomosis.

Since the systemic drugs have been used to reduce the hyperplasic response in the tunica intima, the periadventitial local drug applications to the vascular wall have gained more popularity. In this study, we investigated the effect of bovine serum albumin-glutaraldehyde and polyethylene glycol polymer on neointimal hyperplasia in rabbit carotid artery anastomosis to explore the effects of these two different agents. 21 New Zealand male rabbits were randomly divided into three groups. The carotid artery transection and anastomosis was performed onthe control group. The bovine serum albumin-glutaraldehyde and the polyethylene glycol polymer were applied locally on the other two groups seperatley after transection and anastomosis of the carotid arteries. At the end of 28-day follow-up, the histological and the immunohistochemical results related to neointimal hyperplasia were compared. The glue residues were detected in the BSA-glutaraldehyde group, but in the PEG polymer group there was no glue residue. The intima thickness and the intima/media thickness ratio in the control group was significantly higher (p<0.05) than the other groups. These values did not differ significantly between the BSA-glutaraldehyde group and the PEG polymer group (p>0.05). The lumen diameter and the area in the control group were significantly higher (p < 0.05) than the BSA-glutaraldehyde group. These values between the control group and the PEG polymer group did not differ significantly (p>0.05). aSMA-positive staining score in the Control group was found to be significantly lower (p < 0.05) than the BSA-glutaraldehyde and PEG polymer group and the VEGF-positive staining score in the control group was found to be significantly higher (p < 0.05) than the BSA-glutaraldehyde and the PEG polymer group. Although the both agents have positive results on neointimal hyperplasia, it would be favorable to use polyethylene glycol polymer, since it does not seem to affect the lumen area and the lumen diameter of the vessel.

Redox/NIR dual-responsive PEG-betulinic acid/pluronic-cypate prodrug micelles for chemophotothermal therapy

Betulinic acid (BA) is a new class of anticancer drug, but its relatively short half-life and poor water solubility limit its therapeutic effect and clinical application. Herein, to tackle the dilemma, BA prodrugs were prepared by conjugating BA onto the polyethylene glycol (PEG) polymer via cleavable disulfide bonds. The prodrugs exhibited high water solubility (270-fold of free BA) and a relatively high drug-loading efficiency of 14.2 %. To further endow the BA prodrugs with a photothermal therapeutic effect, the near-infrared (NIR) agent Cypate was grafted on the Pluronic triblock copolymer. The different PEG polymers and different Pluronic polymers were chosen to obtain the optimal drug loading efficiency and the photothermal generation effect. The P-SS-BA/F68-Cy prodrug micelles integrate the redox-responsive BA prodrugs and the NIR-responsive amphiphilic triblock polymer into one single nanocomposite. The release of BA was less than 20 % in pH 7.4 PBS in the absence of glutathione (GSH), whereas the release of BA was obviously accelerated in pH 5.0 PBS with 10 mM GSH. In addition, the release of BA was further accelerated under the NIR irradiation. The P-SS-BA/F68-Cy micelles showed an excellent photothermal heating effect under NIR irradiation. The prepared P-SS-BA/F68-Cy micelles showed the synergistic thermochemotherapeutic effect on tumors both in vitro and in vivo. Therefore, the present study shows the great potential of dual-triggered drug delivery and thermochemotherapy for combination therapy.

Probing effects of additives on the filterability of oncolytic viruses via a microfiltration process

One major part of therapeutic oncolytic viruses (OV) manufacturing is a membrane-based process with a major challenge of membrane fouling and consequent product loss. A small-scale microfiltration setup was developed, allowing online transmembrane pressure (TMP) measurement through a constant flux filtration using a low volume of a representative OV solution (< 3 mL). Using this setup, the effects of different additives including various proteins (bovine serum albumin and alpha-lactalbumin) and organic polymers (polyethylene glycol and polyvinylpyrrolidone) on microfiltration of the OV solution were screened. Results demonstrated that examined proteins significantly decreased membrane fouling rates and increased the virus recoveries. An addition of 5% bovine serum albumin (BSA) to the virus solution increased the virus recovery about 6-times compared to microfiltration of the virus solution without any additive. In contrast, none of the organic polymers could imitate effects of the protein additives. In a separate set of experiment, to study effect of protein on the membrane surface, the membrane surface was pre-blocked using a BSA protein solution and then subsequently utilized to filter the virus solution. This result also demonstrated a significant increase in virus recovery through the blocked membrane, about 4-times higher virus recovery compared to a non-blocked membrane.

Antimicrobial Polymer-Peptide Conjugates Based on Maximin H5 and PEG to Prevent Biofouling of E. coli and P. aeruginosa.

Many pathogens, such as Pseudomonas aeruginosa and Escherichia coli bacteria can easily attach to surfaces and form stable biofilms. The formation of such biofilms in surfaces presents a problem in environmental, biomedical, and industrial processes, among many others. Aiming to provide a plausible solution to this issue, the anionic and hydrophobic peptide Maximin H5 C-terminally deaminated isoform (MH5C) has been modified with a cysteine in the C-terminal (MH5C-Cys) and coupled to polyethylene glycol (PEG) polymers of varying sizes (i.e., 2 kDa and 5 kDa) to serve as a surface protective coating. Briefly, the MH5C-Cys was bioconjugated to PEG and purified by size exclusion chromatography while the reaction was confirmed via SDS-PAGE and MALDI ToF. Moreover, the preventive antimicrobial activity of the MH5C-Cys-PEG conjugates was performed via the growth curves method, showing inhibition of bacterial growth after 24 h. The efficacy of these peptide-polymer conjugates was extensively characterized via scanning electron microscopy (SEM), minimum inhibition concentration (MIC), minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC) assays to evaluate their ability to eradicate and prevent the biofilms. Interestingly, this work demonstrated a critical PEG polymer weight of 5 kDa as ideal when coupled to the peptide to achieve inhibition and eradication of the biofilm formation in both bacteria strains. According to the MICs (40 μM) and MBICs (300 μM), we can conclude that this conjugate (MH5C-Cys-5 kDa) has an action that prevents/inhibits the formation of biofilms and the eradication of biofilms (MBEC 500 μM). In contrast, the MH5C-Cys peptide with PEG polymer of 2 kDa did not show inhibition or eradication of the biofilms.

Slip transition in dynamic wetting for a generalized Navier boundary condition

HypothesisComputer fluid dynamics simulations of dynamic wetting are often performed using a slip model on the substrate. In previous studies, the generalized Navier boundary condition (GNBC) has shown promising results and could help clear the gap between molecular and continuum scales, but lacks quantitative comparisons to experiments. We seek to investigate the dependence between the contact-line velocity and the slip length in a GNBC, by confronting numerical simulations to experimental data. ExperimentsThe physical properties of a molten polymer (polyethylene glycol) were assessed thoroughly. Its dynamic contact angle on a cellulosic substrate was measured carefully using the Wilhelmy method. The experiment was reproduced in a finite elements model using a GNBC. It was repeated for capillary numbers between 10−6 and 10−1, and slip lengths ranging from 1 μm to 1 mm. FindingsA realistic value of the slip length was selected by matching the dynamic contact angles issued from numerical simulations and their experimental counterparts. The slip length behavior as a function of contact line velocity displayed a clear transition. The model also reproduced a dynamic wetting transition between frictional and viscous dissipations, which seems to be linked to an increasing difference between microscopic and macroscopic contact angles.

Purification of xylanase from Aspergillus niger NRRL3 extract by an integrated strategy based on aqueous two-phase systems followed by ion exchange chromatography

Xylanases are enzymes that degrade the linear polysaccharide xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cell walls. Xylanases are applied in a wide range of industrial processes, such as in the pulp and paper industry, which demands a higher purity degree compared to other industries. Processes for the purification of this enzyme has been widely reported using different techniques. However, cases involving the use of a simple combination of unit operations are not common. The objective of this work was to design an integrated bioseparation strategy for the purification of a fungal cellulase-free xylanase. The design consisted of a liquid-liquid extraction using two-combined aqueous two-phase system (ATPS) with an ion exchange chromatography. The effect of different parameters such as polymer type (ethylene oxide-propylene oxide copolymer (UCON) and polyethylene glycol (PEG)), PEG molecular mass (600, 1450, 2000 and 4600 g/mol), volume ratio and the addition of sodium chloride on the enzymes -from the Aspergillus niger NRRL3 extract- partition coefficient were analyzed. The partition behavior of the target product was affected for the type and molecular mass of the polymer used. Extraction using UCON/Citrate system combined with a second extraction using PEG1450/Citrate system proved to be the most suitable for the extraction of xylanase and natural fungal pigments. The enzymatic activity recovery and purification factor achieved were 80% and 4, respectively. The proposed systems have the ability to recycle the UCON and Citrate salt for their reuse in new ATPS. The phases of the combined extraction by ATPS and the elution obtained from ion exchange chromatography were characterized by nano-LC–MS/MS, providing a complete profile of the proteins present. The combination of ATPS with ion exchange chromatography using a Q-Sepharose XL column reached a total enzymatic activity recovery of 79.9% and a purification factor of 11. This is the first time that high-quality xylanase free of cellulolytic enzymes is reported using an integrated bioprocess strategy with potential for industrial adoption.

Application of poly(2-methyl-2-oxazoline) in protein separation by capillary electrophoresis

Capillary electrophoresis (CE), a commonly used liquid-phase separation technology, has many advantages such as high analysis speed, high separation efficiency, and low sample consumption. Hence, CE has gained popularity in food analysis, medical clinical diagnosis, environmental monitoring, and biological sample separation, especially in the field of protein separation and analysis. However, the fused silica capillaries that are commonly used in CE easily adsorb proteins, resulting in unstable electroosmotic flow and poor reproducibility of the separation results. In addition, due to the short optical path of the typical ultraviolet detectors employed in commercial CE, the detection sensitivity often does not meet the requirements for the direct analysis of low-abundance proteins. Therefore, developing a coating that can prevent protein adsorption and improve detection sensitivity is one of the important challenges in CE separation and analysis of proteins. Poly(2-methyl-2-oxazoline), a peptide-like hydrophilic polymer, not only has hydrophilicity, protein-repellent ability, and biocompatibility similar to the gold standard of the anti-protein adsorption polymer (polyethylene glycol), but also shows better stability than polyethylene glycol due to its peptide-like structure. Therefore, it has been increasingly used in biomass transfer, drug carrier, and impedance protein adsorption in recent years. This article aims to review the recent applications of poly(2-methyl-2-oxazoline) in CE from two standpoints. First, poly(2-methyl-2-oxazoline) was grafted onto the capillary inner wall using polydopamine as an anchor. The resulting coated capillary successfully separated a mixture of proteins (such as lysozyme, cytochrome C, ribonuclease A, and α -pancreas chymosinogen A), in addition to preventing the non-specific adsorption of other proteins during the quantitative analysis of melamine and lactoferrin in milk powder. Thus, the detection efficiency of melamine and lactoferrin in milk powder was improved. Second, poly(2-methyl-2-oxazoline) was used to produce a binary mixed brush coating with a stimulus-responsive polymer (such as polyacrylic acid). The capillary coated with the mixed brushes could adsorb high amounts of the target protein (such as bovine serum albumin and lysozyme) under certain pH and ionic strength conditions, and most of the adsorbed proteins could be desorbed by changing the pH and ionic strength. During the release, poly(2-methyl-2-oxazoline) present on the coating would prevent the adsorption of proteins. Under the dual effects of electroosmotic flow and electrophoresis, the released protein could migrate rapidly, and the instantaneous concentration of the protein reaching the detector could be greatly increased. Therefore, the target proteins could be on-line concentrated and the detection signals could be amplified, resulting in improved detection sensitivity for the protein. Future development trends in the function of poly(2-methyl-2-oxazoline) for the separation of proteins by CE are also discussed.

Structure of an anti-PEG antibody reveals an open ring that captures highly flexible PEG polymers

Polyethylene glycol (PEG) is a polymer routinely used to modify biologics and nanoparticles to prolong blood circulation and reduce immunogenicity of the underlying therapeutic. However, several PEGylated therapeutics induce the development of anti-PEG antibodies (APA), leading to reduced efficacy and increased adverse events. Given the highly flexible structure of PEG, how APA specifically bind PEG remains poorly understood. Here, we report a crystal structure illustrating the structural properties and conformation of the APA 6-3 Fab bound to the backbone of PEG. The structure reveals an open ring-like sub-structure in the Fab paratope, whereby PEG backbone is captured and then stabilized via Van der Waals interactions along the interior and exterior of the ring paratope surface. Our finding illustrates a strategy by which antibodies can bind highly flexible repeated structures that lack fixed conformations, such as polymers. This also substantially advances our understanding of the humoral immune response generated against PEG.

RETRACTED ARTICLE: Understanding mechanical characteristics of pH-responsive PEG 4000-based polymeric network for colorectal carcinoma: its acute oral toxicity study

The major objective of this study is to fabricate a very promising system by loading anticancer agent in it which could be given to the cancer patients by oral administration and additionally that will liberate drugs in large intestine (affected/cancerous area). Minimum or no exposure of chemotherapeutic agents to gastric/small intestine will significantly eliminate the problem of adverse drug reactions. Cancer patients are facing severe problem of side/adverse effects due to intravenous colorectal carcinoma chemotherapy. So, an oral drug delivery system is designed to substitute the intravenous drug therapy. This study reports the synthesis of hybrid polymeric polyethylene glycol hydrogels (PEGA 4000) based on acrylic acid (AA), ammonium peroxodisulfate and ethylene glycol dimethacrylate (EGDMA) by solution polymerization method. PEGA 4000 hydrogels were used for colon targeting of hydrophilic anti-carcinoma drug (oxaliplatin). Development of new structure was confirmed by Fourier transform infrared spectroscopy. Surface morphology of developed hydrogel slabs was examined by scanning electron microscopy. Thermal gravimetric analysis of hydrogels revealed that there was an increase in thermal stability of PEGA 4000 hydrogels. Swelling study was performed in acidic and basic pH medium provided important information on drug release characteristics of hydrogels. The release of oxaliplatin (OXP) was significantly retarded at pH 1.2, while rapid release was observed at pH 7.4. The release rate of OXP increased with increasing concentration of PEG 4000 and AA. However, extent of drug release was significantly reduced on increasing concentration of EGDMA. Mechanism of release has been evaluated by applying various mathematical kinetic models. The tensile mechanical strength and elongation at break were also observed on different formulations based on various ratios of reaction contents. The consequents of our study suggest that fabricated PEGA 4000 hydrogels could serve as suitable target release delivery system and toxicity study endorsed biocompatibility of hydrogels to biological system.

Data on the removal of peroxides from functionalized polyethylene glycol (PEG) and effects on the stability and sensitivity of resulting PEGylated conjugates.

Cyanine-5 (Cy5) is a fluorescent dye active in the far-red region of the visible spectrum (λex = 646 nm, λem = 662 nm) [1]. While Cy5 displays fluorescence in its oxidized form, it can be readily converted to its non-fluorescent hydrocyanine equivalent (H-Cy5) when exposed to reducing agents. H-Cy5 can then be converted back to its fluorescent oxidized form when exposed to reactive oxygen species (ROS), allowing it to act as a highly sensitive, high wavelength fluorescent ROS sensor [2]. However, H-Cy5 is a small, poorly water-soluble molecule, and is rapidly taken up into cells in vivo, preventing its use for sensing extracellular ROS, which are implicated in inflammation, wound healing, and other processes [3], [4], [5], [6]. A solution to this lies in the conjugation of Cy5 to a polyethylene glycol (PEG) polymer, increasing its solubility [7]. This conjugate (Cy5-PEG) can be reduced to H-Cy5-PEG to allow the highly sensitive detection of ROS in an aqueous extracellular environment. However, after PEG conjugation, a significant decrease in stability and sensitivity is observed, likely owing to the presence of ROS contaminants in commercial samples of PEG. It has been reported that these ROS impurities can be removed from PEG through a simple freeze-drying procedure [8]. Here, we demonstrate that a simple, straightforward method for the purification of PEG can allow the synthesis of a highly functional, water-soluble ROS sensor that could be used for extracellular ROS sensing.

On the Influence of Additives of Polymer, Sodium Nitrate, and 1-Methyl-2-Pyrrolidone on the Extraction of Thiophene in an n-Hexan–Water System

The effect of individual and multicomponent additives—water-soluble polymers (polyethylene glycol 400, polypropylene glycol 425, and polyvinylpyrrolidone 3500), sodium nitrate, and 1-methyl-2-pyrrolidone—on the extraction of thiophene in an n-hexane–water system has been studied. It is found that, in most cases, the introduction of small amounts of additives into the extraction system leads to a significant increase in the degree of extraction of thiophene from n-hexane in the aqueous phase in comparison with the individual components.