Chapter

Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications

January 1992

In book: Poly(Ethylene Glycol) Chemistry (pp.1-14)

Authors:

At first glance, the polymer known as poly(ethylene glycol) or PEG appears to be a simple molecule. It is a linear or branched, neutral polyether, available in a variety of MWs, and soluble in water and most organic solvents. Despite its apparent simplicity, $${HO - {{\left( {C{H_2}C{H_2}O} \right)}_n} - C{H_2}C{H_2}OH} \hfill \\ {poly(ethylene\,glycol)}$$ this molecule is the focus of much interest in the biotechnical and biomedical communities. Primarily this is because PEG is unusually effective at excluding other polymers from its presence when in an aqueous environment. This property translates into protein rejection, formation of two-phase systems with other polymers, nonimmunogenicity, and nonantigenicity. In addition, the polymer is nontoxic and does not harm active proteins or cells although it interacts with cell membranes. It is subject to ready chemical modification and attachment to other molecules and surfaces, and when attached to other molecules it has little effect on their chemistry but controls their solubility and increases their size. These properties, which are described in more detail below, have led to a variety of important biotechnical and biomedical applications, a summary of which is also presented below.

PEG: Will It Come Back to You? Polyethelyne Glycol Immunogenicity, COVID Vaccines, and the Case for New PEG Derivatives and Alternatives

Article

Full-text available

Apr 2022

Élaboration de vecteurs d'ADN, substrats de gélatinases

Thesis

Jun 2005

Yves Lelièvre

Un peptide synthétique, substrat de gélatinases A (MMP2) et B (MMP9 a été introduit par synthèses chimiques diverses entre deux polymères : une poly(éthyleneimine), (L-PEI) et un poly(éthylène glycol)5000, (mPEG5000). La conception des produits est basée sur l’inhibition de la transfection cellulaire d’ADN lié au L-PEI, par le mPEG, lorsque le peptide incorporé n’est pas clivé par ces enzymes. Un taux plus important de transfection du gène de la luciférase, transporté par ces substrats, est obtenu avec les cellules HT1080 qu’avec les cellules B16 et 3T3, alors que pas ou peu de transfection est obtenue avec les molécules-témoins. Ces résultats sont en rapport avec les activités gélatinases des surnageants de ces cellules, permettant l’élimination du mPEG. Ils laissent envisager un ciblage de gènes thérapeutiques de cellules cancéreuses avec un vecteur synthétique.

Hydrophilic polymer‐coated PVC surface for reduced cell and bacterial adhesions

Article

Full-text available

Feb 2022

Abstract Hydrophilic polymers are very useful in biomedical applications. In this study, biocompatible polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) polymers end‐capped with succinimidyl groups were either modified or synthesised and attached to polyvinylchloride surfaces. The modified surfaces were evaluated with cell adhesion and bacterial adhesion. 3T3 mouse fibroblast cells and three bacteria species were used to evaluate surface adhesion activity. Results showed that the modified surface exhibited significantly reduced 3T3 cell adhesion with a 50%–69% decrease for PEG and a 64%–81% for PVP, as compared to unmodified polyvinylchloride. The modified surface also showed significantly reduced bacterial attachment with 22%–78%, 18%–76% and 20%–75% decrease for PEG and 22%–76%, 18%–76% and 20%–73% for PVP to Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, respectively, as compared to unmodified polyvinylchloride. It seems that an appropriate chain length or molecular weight (neither the longest nor the shortest chain length) determines the lowest cell and bacterial adhesion in terms of PEG. On the other hand, a mixture of polymers with different chain lengths exhibited the lowest cell and bacterial adhesion in terms of PVP.

Probing Protein Nanopores with Poly(ethylene glycol)s

Article

Full-text available

Jan 2022

Neutral water-soluble poly(ethylene glycol)s (PEGs) have been extensively explored in protein nanopore research for the past several decades. The principal use of PEGs is to investigate the membrane protein ion channel physical characteristics and transport properties. In addition, protein nanopores are used to study polymer-protein interactions and polymer physicochemical properties. In this review, we focus on the biophysical studies on probing protein ion channels with PEGs, specifically on nanopore sizing by PEG partitioning. We discuss the fluctuation analysis of ion channel currents in response to the PEGs moving within their confined geometries. The advantages, limitations, and recent developments of the approach are also addressed. This article is protected by copyright. All rights reserved.

Développement de supports d’immobilisation biosourcés pour la dégradation enzymatique de micropolluants dans un réacteur à lit fluidisé

Thesis

Nov 2020

Marine Harguindeguy

Ce travail de thèse a pour objectif l’élaboration de supports d’immobilisation d’enzymes bio sourcés en vue de la dégradation de micropolluants dans l’eau. Des billes de gélatine de diamètre moyen 1,9 mm ont été formées dans ce but par un procédé de goutte à goutte n’employant aucun solvant organique. La réticulation des billes par le glutaraldéhyde permet d’une part de limiter le gonflement de ce polymère dans l’eau et d’améliorer sa tenue mécanique en immersion, et d’autre part de créer des liaisons covalentes entre la gélatine et la laccase. Un plan d’expérience 2^4 a été réalisé afin d’identifier les paramètres influant sur l’efficacité du greffage.La dégradation de deux micropolluants par les billes activées a été étudiée en réacteur agité et dans un réacteur à lit fluidisé conçu pour ce projet. La tétracycline s’est montrée sensible à l’oxydation par les laccases greffées à la surface des billes. Divers paramètres ont été étudiés comme le pH de la solution, le débit de recirculation, ou l’addition d’oxygène dans le système. Le glyphosate s’est montré plus récalcitrant à l’action de la laccase seule à cause d’une structure plus complexe. L’ajout d’un médiateur d’oxydoréduction, l’ABTS, a néanmoins permis de faciliter son oxydation. La co-immobilisation du médiateur et du biocatalyseur sur les supports à base de gélatine a été étudiée, afin de limiter l’impact économique et environnemental du projet.

Hydration Numbers of Polyethylene Glycols Based on a New Viscosity Model

Article

Jun 2023

Hakim Fikret Abbasov

Due to the high solubility in water and the structural compatibility of polyethylene glycol with water molecules, it is a good model system for studying the mechanisms of interaction between water and biopolymers. The behavior of biopolymers in living organisms strongly depends on the hydration of macromolecules in the aquatic environment. In this work the effective hydration numbers of polyethylene glycols are determined using a new viscosity model developed for electrolytes and experimental data on the viscosity of dilute aqueous solutions of polyethylene glycols (300–35000). The calculated hydration numbers are in good agreement with the literature data and increase with increasing molecular mass of polyethylene glycol: as the molecular mass increases, starting from a molecular mass of 1000, the chain begins to fold in on itself, forming segment-segment interactions, trapping additional, more loosely bound water between the segments. Based on the dependence of the intrinsic viscosity on the molecular mass according to the Mark-Houwink equation, it is shown that PEGs are the flexible polymers and highly soluble in water.

3D Printing as a Technological Strategy for the Personalized Treatment of Wound Healing

Article

Jan 2023
AAPS PHARMSCITECH

Wound healing is a dynamic process which involves stages of hemostasis, inflammation, proliferation and remodeling. Any error in this process results in abnormal wound healing, generating financial burdens for health systems and even affecting the physical and mental health of the patient. Traditional dressings do not meet the complexities of ideal treatment in all types of wounds. For this reason, in the last decades, different materials for drug delivery and for the treatment of wounds have been proposed reaching novel level of standards, such as 3D printing techniques. The use of natural or synthetic polymers, and the correct design of these printed products loaded with cells and/or combined with active compounds, can generate an effective system for the treatment of wounds, improving the healing process and generating customized dressings according to the patient needs. This manuscript provides a comprehensive review of different types of 3D printing techniques, as well as its use in wound healing and its different stages, including the advantages and limitations of additive manufacturing and future perspectives.Graphical abstract

Amphiphilic nonionic block and gradient copoly(2-oxazoline)s based on 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline as efficient stabilizers for the formulation of tailor-made emulsions

Article

Nov 2022
J COLLOID INTERF SCI

Hypothesis Poly(2-alkyl/aryl-oxazoline)s (PAOx) have seen a resurgence of interest in the new millennium due to their biocompatibility, low toxicity, and higher tunability compared to poly(ethylene glycol) (PEG). Due to the straightforward access to hydrophilic and hydrophobic PAOx, it was hypothesized that amphiphilic PAOx should be capable of stabilizing oil/water (O/W) interfaces. Furthermore, the control of their composition, chain length, and monomer distribution could suggest the formulation of tunable emulsions. Special emphasis was given to evaluate whether spontaneously formed amphiphilic gradient copolymer could stabilize O/W emulsions. Experiments We prepared a series of amphiphilic block and gradient copolymers based on 2-methyl-2-oxazoline and 2-phenyl-2-oxazoline with variable hydrophilic/lipophilic balance, degree of polymerization, and monomer distribution as basis to explore their ability to stabilize emulsions. Systematic granulometry, stability, and rheology studies were performed to characterize the final emulsions. Findings Remarkably, stable O/W emulsions are obtained with only 0.5 wt.% of copolymers. The finer emulsions stabilized by the most hydrophilic copoly(2-oxazoline)s allow an adjustment of their texture, as well as the concentration increase and oil content. Importantly, emulsion properties prepared with gradient copolymers show similar behavior compared with their block counterparts offering easy access to new biocompatible emulsifiers as these gradient copolymers are spontaneously formed by statistical copolymerization.

Bio-inspired special wettability in oral antibacterial applications

Article

Full-text available

Aug 2022

Most oral diseases originate from biofilms whose formation is originated from the adhesion of salivary proteins and pioneer bacteria. Therefore, antimicrobial materials are mainly based on bactericidal methods, most of which have drug resistance and toxicity. Natural antifouling surfaces inspire new antibacterial strategies. The super wettable surfaces of lotus leaves and fish scales prompt design of biomimetic oral materials covered or mixed with super wettable materials to prevent adhesion. Bioinspired slippery surfaces come from pitcher plants, whose porous surfaces are infiltrated with lubricating liquid to form superhydrophobic surfaces to reduce the contact with liquids. It is believed that these new methods could provide promising directions for oral antimicrobial practice, improving antimicrobial efficacy.

A Transient Initiator for Polypeptoids Post‐Polymerization α‐Functionalization via Activation of a Thioester Group

Article

Full-text available

Dec 2021

Here we introduce a post-polymerization modification method of an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine. We utilized 4-(methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity and high end-group fidelity, as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectroscopy. The introduced method could be of great interest for bioconjugation, but requires optimization, especially for protein conjugation. This article is protected by copyright. All rights reserved

A transient initiator for polypeptoids post-polymerization α-functionalization via activation of thioester group

Preprint

Full-text available

Sep 2021

Conception et élaboration de matériaux à biodégradabilité contrôlée pour la médecine régénérative

Thesis

Full-text available

Dec 2017

Mathieu Goczkowski

Fibrin gels are of interest in regenerative medicine, as they mimic the provisory matrix synthesized during wound healing process. However, when prepared at physiologic concentration, these gels cannot be handled, nor stocked in dry state. To face these drawbacks, they can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN). This strategy was used to associate to a fibrin network, a semi-synthetic conetwork composed of bovine serum albumin (BSA) and poly(ethylene oxide) (PEO), obtained by photopolymerization of methacrylate-modified BSA and PEG. It was demonstrated through ex vivo and in in vitro experiments that these materials have numerous potential applications, as they support on their surface, the culture of numerous cell types. Moreover, it was observed that they may be used as drug carrier for drug release applications. Moreover, the technology was optimized by modifying the methacrylate functions on the precursors for acrylate functions. This modification allowed to reduce the toxicity of the process, while preserving materials performances. It was also demonstrated that these optimized materials have different degradation mechanisms, which are controllable by their initial formulation. Finally, 2 new groups of fibrin-based IPNs were developed, by associating to a fibrin network, another protein network, the silk fibroin. Perfectly manipulable IPNs were obtained, which support on their surface the culture of fibroblasts. These materials are then very promising for skin tissue engineering, and most likely other applications.

Bioactive peptides for boosting stem cell culture platform: Methods and applications

Article

Full-text available

Feb 2023

Peptides, short protein fragments, can emulate the functions of their full-length native counterparts. Peptides are considered potent recombinant protein alternatives due to their specificity, high stability, low production cost, and ability to be easily tailored and immobilized. Stem cell proliferation and differentiation processes are orchestrated by an intricate interaction between numerous growth factors and proteins and their target receptors and ligands. Various growth factors, functional proteins, and cellular matrix-derived peptides efficiently enhance stem cell adhesion, proliferation, and directed differentiation. For that, peptides can be immobilized on a culture plate or conjugated to scaffolds, such as hydrogels or synthetic matrices. In this review, we assess the applications of a variety of peptides in stem cell adhesion, culture, organoid assembly, proliferation, and differentiation, describing the shortcomings of recombinant proteins and their full-length counterparts. Furthermore, we discuss the challenges of peptide applications in stem cell culture and materials design, as well as provide a brief outlook on future directions to advance peptide applications in boosting stem cell quality and scalability for clinical applications in tissue regeneration.

Advances in the development and optimization strategies of the hemostatic biomaterials

Article

Full-text available

Jan 2023

Most injuries are accompanied by acute bleeding. Hemostasis is necessary to relieve pain and reduce mortality in these accidents. In recent years, the traditional hemostatic materials, including inorganic, protein-based, polysaccharide-based and synthetic materials have been widely used in the clinic. The most prominent of these are biodegradable collagen sponges (Helistat®, United States), gelatin sponges (Ethicon®, SURGIFOAM®, United States), chitosan (AllaQuixTM, ChitoSAMTM, United States), cellulose (Tabotamp®, SURGICEL®, United States), and the newly investigated extracellular matrix gels, etc. Although these materials have excellent hemostatic properties, they also have their advantages and disadvantages. In this review, the performance characteristics, hemostatic effects, applications and hemostatic mechanisms of various biomaterials mentioned above are presented, followed by several strategies to improve hemostasis, including modification of single materials, blending of multiple materials, design of self-assembled peptides and their hybrid materials. Finally, the exploration of more novel hemostatic biomaterials and relative coagulation mechanisms will be essential for future research on hemostatic methods.

Fluctuations in channel transport across multiple lengthscales

Thesis

Jul 2022

Stuart Knowles

Channel transport is an important physical process, with relevance to diverse fields from cell biology to single molecule sensors, catalysts and filters. Given the ubiquitous nature of channel transport phenomena, achieving a deep understanding of their governing dynamics is ever more desirable. Experimental model systems provide powerful platforms to probe these dynamics. This thesis presents experimental investigations into the fundamental phenomena governing transport through confining channels, in particular the role of fluctuations in such processes. In sensing fields, fluctuations, or noise, are considered undesirable, however careful study of their spectral composition can yield deep insight into underlying physical mechanisms. To achieve a broad understanding over multiple length scales, two experimental models are exploited: the first centred on probing currents of ions through nanoscale glass pores and the second, the flow of colloidal particles through a microfluidic channel. Studies in nanopores begin with an investigation into the intrinsic fluctuations in the ionic current flowing through the pore. A careful study of the 1/f noise present at low frequencies shows that this regime is dominated by fluctuations in the surface current rather than bulk current. Building on this, fluctuations associated with polymer adsorption in the pores are considered. It is found that adsorption generates a characteristic change in current fluctuations which depends sensitively on experimental conditions. Careful analysis of the change in fluctuations yields information on the underlying shape of the adsorption potential on the scale of a single polymer. Next, to probe fluctuations in observable currents of particles, colloidal flow through microfluidic channels is studied using optical microscopy. By using colloids which sediment into a quasi-2D monolayer, the entire transport process can be visualised in detail. To characterise the system, the capture dynamics in two different microfluidic geometries is probed. The importance of long range behaviour to the capture process is demonstrated by showing that drastically different capture rates can be achieved even when conditions within the channel itself are held constant. Fluctuations in the colloidal currents through microchannels are then studied. We start with a model from classical electronics for shot noise in a system with a single characteristic transit time, which is then modified to account for a distribution of transit times, arising from the distribution of particle speeds within the channel. Excellent agreement is found between the spectra of fluctuations for measured currents and those predicted by the modified model, with the particle speed distribution representing the key input into the model. By presenting a series of studies in multiple experimental model systems, this work represents an advancement in the understanding of channel transport fluctuations, and demonstrates the untapped potential of fluctuations analysis as a method of probing physical processes at the micro- and nano-scale. Characterising these systems lays the groundwork for further studies of fluctuating transport in the future, opening the door to more detailed models of molecular transport, cellular processes, and all confined motion on the sub-micrometre scale.

Influence of the Molecular Weight of Poly (Ethylene Glycol) on the Aqueous Dispersion State of Magnetic Nanoparticles: Experiments and Monte Carlo Simulation

Article

Full-text available

Oct 2022
J CLUST SCI

Here, we used experiments and Monte Carlo simulations (MC) to identify appropriate poly (ethylene) glycol (PEG) polymer molecular weight (Mw) as the coating agent for iron oxide nanoparticles (IONPs) resulting in individual particles in water. IONPs coated with PEG Mw’s ranging from 1500 to 6000 Da showed highly stable dispersions for more than a year. Transmission electron microscopy (TEM) results of the dispersions revealed that particles coated with lower PEG Mw were aggregated, which shifted to individual form with increasing PEG Mw used for coating. We find that this transformation is due to increased PEG layer shell thickness (from 1.47 to 6.46 nm) with increasing PEG Mw (from 1500 to 6000 Da), which imparted sufficient repulsive steric forces to overcome the attractive van der Waals and magnetic forces. To predict appropriate PEG Mw resulting individual IONPs in water, the number density distribution of different PEG Mw coated particles was determined using MC simulation which employs interparticle potentials between the interacting particles as a function of their interparticle distance. The predictions gave very good agreement with our’s and others’ experimental data. Thus, the study helps to identify a suitable polymer Mw as a coating agent, resulting in individual nanoparticle dispersion.

Immunomodulatory properties of D-sorbitol/D-mannitol incorporated linear step-growth Co -polymers

Article

Mar 2022

A range of D-sorbitol/D-mannitol incorporated co-polymers were synthesized via solvent free enzyme catalyzed polycondensation with adipic acid and polyethylene glycol. In-vitro cytotoxic studies on breast cancer and fibroblast cell lines showed that the co-polymers are biocompatible up to 500 and 250 µg/mL, respectively. However, THP-1 and RAW 264.7 cell lines showed a dose dependent cytotoxicity. Furthermore, these co-polymers did not produce excessive cytokines (TNFα/IL-6) and chemokines (CXCL-5/CXCL-10) when interacting with THP-1 cells, thereby, not causing any inflammation. Whilst, the expression of IL-1b, CXCL-1 and IFNβ were upregulated. The results suggest that these co-polymers could be promising vaccine adjuvants.

Gold nanoprobe exploring the novel ice structure in the aqueous dispersion of poly(ethylene glycol)-gold hybrid nanoparticle

Article

Feb 2022
LANGMUIR

Controlled delivery of quantum dots using microelectrophoresis technique: Intracellular behavior and preservation of cell viability

Article

Dec 2021
BIOELECTROCHEMISTRY

The use of synthetic nanomaterials as contrast agents, sensors, and drug delivery vehicles in biological research primarily requires effective approaches for intracellular delivery. Recently, the well-accepted microelectrophoresis technique has been reported to exhibit the ability to deliver nanomaterials, quantum dots (QDs) as an example, into live cells, but information about cell viability and intracellular fate of delivered nanomaterials is yet to be provided. Here we show that cell viability following microelectrophoresis of QDs is strongly correlated with the amount of delivered QDs, which can be finely controlled by tuning the ejection duration to maintain long-term cell survival. We reveal that microelectrophoretic delivered QDs distribute homogeneously and present pure Brownian diffusion inside the cytoplasm without endosomal entrapment, having great potential for the study of dynamic intracellular events. We validate that microelectrophoresis is a powerful technique for the effective intracellular delivery of QDs and potentially various functional nanomaterials in biological research.

Preventing Pseudomonas aeruginosa Biofilms on Indwelling Catheters by Surface-Bound Enzymes

Article

Nov 2021

Mechanism of shales stabilization by hydrophobized poly(ethylene glycol)/K+ in water-base drilling fluids

Article

Full-text available

Jun 2021

The mechanism of the hydrophobized poly(ethylene glycol) (PEG)/K⁺ system inhibiting shale hydration was studied by laboratory experiment. The inhibition performance was evaluated through cuttings hot-rolling dispersion, bentonite inhibition and contact angle tests. The inhibition became stronger as contact angle and PEG concentration increased. A modified cuttings hot-rolling dispersion experiment suggested that these molecular systems did not act through the thermally activated mud emulsion (TAME) mechanism. The interaction of the PEG/K⁺ with clay samples was investigated through adsorption studies and by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The adsorption isotherms showed that the presence of K⁺ increased the PEG affinity for the clay surface. This inhibition effect was accompanied by a reduction of the bentonite hydration with PEG adsorption, evidenced by FT-IR, TGA and differential thermogravimetric (DTG) curves. XRD patterns were conclusive in showing that the presence of K⁺ ions limited the expansion of the clay interlamellar region to only one PEG layer, and the terminal hydrophobic segments of the PEG chains turned out to be determinant in enhancement of the inhibitory efficiency. The cuttings hot-rolling dispersion was carried out on water-base drilling fluid with PEG/K⁺, which proved the inhibition performance of PEG/K⁺ in oil field drilling.

Water decontamination using bio-based, chemically functionalized, doped, and ionic liquid-enhanced adsorbents: review

Article

Mar 2021

The access to clean water is a critical issue in the context of climate change and worldwide pollution, calling for advanced methods of purification. Recent advances in materials science, nanoscience, and analytical chemistry have led to the design of novel nanoadsorbents having a unique properties, structure, and adsorption performances. In particular, research has focused on all-inclusive adsorbents which can remove different contaminants simultaneously. Here, we review the adsorption dynamics of doped, ionic liquid-enhanced, bio-based, and chemically functionalized materials. We examine their characteristics, underlying principles of adsorption, and their potential limitations in adsorbing various metal ions and xenobiotics. We found that chemical functionalization with specific organic moieties is a preferred approach for enhancing the adsorption capacities and selectivity of raw materials. Moreover, doping can also modulate the morphology, electronic structure, and surface chemistry for higher performance. Ionic liquids are promising solvents for the synthesis of stable adsorbents, owing to ionic liquid ability to pull other molecules through hydrogen bonds or electrostatic forces.

Accepted Manuscript Title: Comparative Molecular Dynamic Simulation Study on the Use of Chitosan for Temperature Stabilization of Interferon II

Article

Dec 2020
CARBOHYD POLYM

There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways.

Investigating noise signatures of polymer adsorption using nanopores

Preprint

Dec 2020

The modification of surface properties by polymer adsorption is a widely used technique to tune interactions in molecular experiments, such as resistive pulse sensing with nanopores. Here, we investigate how variation of the ionic current noise through glass nanopores reflects the passive adsorption of short, neutral polymers to the pore surface. We find that the power spectral density of the noise shows a characteristic change upon adsorption of polymer, however the magnitude of this increase is strongly dependent on both polymer length and salt concentration. In particular, for short polymers at low salt concentrations no change in noise is observed, despite verification of comparable adsorption in these systems using quartz crystal microbalance with dissipation monitoring measurements. We propose that the characteristic noise is generated by small current changes associated with the movement of polymers on and off the nanopore surface and perform simple simulations to assess the feasibility of this model. Excellent agreement is obtained with experimental data using physically motivated parameters for the adsorption strength and range, supporting our molecular interpretation of the observed noise signatures in our data. This highlights the value of analysing system fluctuations as a method of elucidating molecular processes, and paves the way to using noise spectral analysis for in situ characterisation of functionalised nanopores.

SPRINGER BRIEFS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY Biomedical Applications of Natural Proteins An Emerging Era in Biomedical Sciences

Chapter

Nov 2020

Sayed Iqbal Ahamad

Abstract Silk sericin is the gum-like protein surrounding the fibroin in silk fibers, and generally it is removed during the fiber processing to produce fabrics. Like other silk proteins, the silk of tasar silkworms is also composed of sericin and fibroin. In this study tasar silk sericin was extracted and was confirmed to be a 70 KDa protein by SDS PAGE. The use of sericin in the field of biomedical applications has increased their use for various purposes, the extracted silk sericin was pegylated with activated PEG (MW 5000) and the conjugated product was characterized by FT-IR, 1H NMR, CD, DSC, XRD, and AF TEM and self-assembled nanoparticles were prepared.

Research progress of biomimetic materials in oral medicine

Article

Full-text available

Nov 2023
J Biol Eng

Biomimetic materials are able to mimic the structure and functional properties of native tissues especially natural oral tissues. They have attracted growing attention for their potential to achieve configurable and functional reconstruction in oral medicine. Though tremendous progress has been made regarding biomimetic materials, significant challenges still remain in terms of controversy on the mechanism of tooth tissue regeneration, lack of options for manufacturing such materials and insufficiency of in vivo experimental tests in related fields. In this review, the biomimetic materials used in oral medicine are summarized systematically, including tooth defect, tooth loss, periodontal diseases and maxillofacial bone defect. Various theoretical foundations of biomimetic materials research are reviewed, introducing the current and pertinent results. The benefits and limitations of these materials are summed up at the same time. Finally, challenges and potential of this field are discussed. This review provides the framework and support for further research in addition to giving a generally novel and fundamental basis for the utilization of biomimetic materials in the future.

Treatment-induced and Pre-existing Anti-peg Antibodies: Prevalence, Clinical Implications, and Future Perspectives

Article

Nov 2023
J PHARM SCI-US

Supplementary material A: Commentaries

Chapter

Mar 2020

Sean Ainsworth

Neonatal Formulary bridges a gap between a standard formulary (stating doses, indications, etc.) and a standard neonatal textbook by expanding information about the conditions for which each drug is used. Much of drug use during pregnancy, lactation, and in neonates and young infants is ‘off license’ (i.e. using licensed drugs but for an indication that is outside the licensed use—in many cases simply because the studies and the licensing application did not include data about neonatal use). The book offers information to allow practitioners to make informed choices whether to use such a drug or not by presenting data from published studies to support such a use. Part 1 concentrates on drug prescribing and drug administration, presenting general information on drug storage, drug licensing, and drug prescribing. It also explains to the reader why the metabolism of drugs differs in premature and sick infants and why the practice of extrapolating doses from adult studies is wrong. Patient safety, excipients, and therapies that affect drug metabolism (such as therapeutic hypothermia) are also covered. Part 2 consists of drug monographs for over 250 drugs that may find use in the neonatal population but which nonetheless may also find use outside the neonatal unit. Each monograph is divided into sections covering use, pharmacology, treatment, drug interactions, or other administration information, supply, and administration, and references. The monographs also contain links to Cochrane Database of Systematic Reviews and national guidelines supported by bodies such as the National Institute for Health and Care Excellence or the Royal Colleges. Part 3 contains brief notes on a range of additional drugs and groups of drugs that are often taken by mothers during pregnancy, labour, or during breast feeding where effects on either the fetus or infant can be seen. This information will help to provide safe and effective prescribing of drugs to all mothers and their babies.

Polymeric Nanoparticles as Theranostics for Targeting Solid Tumors

Chapter

Nov 2022

Nanotechnology allows to develop new approaches for the diagnosis and treatment of cancer. In particular, formulations are developed specifically for the diagnosis purpose. This chapter reviews the development of polymeric theranostic formulations such as polymeric gold nanoparticles, polymeric superparamagnetic nanoparticles, quantum dots-loaded polymeric nanoparticles, dendrimer-loaded polymeric nanoparticles, polymeric micelles, and carbon nanotubes with polymeric nanoparticles. These systems are effective in the treatment of brain cancer, lung cancer, breast cancer, and ovarian cancer.

Recent Advances and Applications of Hydrogels in Medicine

Chapter

Oct 2022

Hossein Hosseinkhani

This chapter discusses current developments concerning recent advances and applications of biomolecule‐responsive hydrogels in medicine via emphasizing this research area with novel literature studies. The discussion is categorized into three main types, namely, glucose‐responsive hydrogels, protein‐responsive hydrogel, and nucleic acid‐responsive hydrogels. The chapter describes their potential applications in drug delivery, cell and cancer research, regenerative medicine and biosensor, and presents some problems as well as the new directions on future developments. Enzyme‐responsive hydrogels are used in the fabrication of degradable biomaterials and native extracellular matrices. Although the ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and the natural nucleic acid‐responsive hydrogels provide the advantages of biocompatibility, they are not stable against temperature and enzymatic cleavage. Peptide nucleic acid, serving as a synthetic nucleic acid not only solved these issues but also indicated stronger binding properties than RNA and DNA.

EIS Technique for Corrosion Study and Analysis

Chapter

Jan 2022

One of the important electrochemical techniques used to investigate corrosion is electrochemical impedance spectroscopy (EIS). It complements the potentiodynamic polarization (PDP) and linear polarization (LP) techniques used in corrosion studies and is nondestructive. EIS can be used to determine the appropriate potential scan rate to be used in PDP and LP and validate the results. After a brief introduction to EIS, experimental aspects and analysis, specifically to characterize corrosion, are described. Applications of EIS in metal corrosion in a variety of environments are illustrated. Coatings are often employed to protect a surface from corrosion. The effectiveness of coating in enhancing the corrosion resistance is frequently evaluated using EIS. Several circuits used to model the impedance data using equivalent electrical circuits are described. The identification of the circuit elements with the physical components or the processes is also explained. The future scope of the application of EIS to corrosion is outlined, and the main advantages and limitations of this technique are summarized.KeywordsElectrochemical impedance spectroscopyEquivalent electrical circuitPolarization resistance

Graphene Oxide Hybrid Coatings on Implant Alloys for Biomedical Applications

Chapter

Jan 2022

Graphene oxide (GO), the oxygenated counterpart of one atom thick graphene sheets, has been applied in various biotechnologies such as biosensor, cellular imaging nano-probe, drug delivery, and so on, due to its extremely large surface area, ease of chemical functionalization, good biocompatibility, and biostability. The use of GO brings outs its dispersion behavior along with its ideal mechanical properties. Nano-hydroxyapatite (n-HAP) is a bioactive calcium phosphate ceramic [Ca10(PO4)6(–OH)2] with chemical and crystallographic similarity to that of apatite phases present in bones. The fragile nature of n-HAP prevents its use as load-bearing implants. On the other hand, polyethylene glycol (PEG) earns its fame because of its high structure flexibility, biocompatibility, amphilicity devoid of any steric hindrances, and high hydration capacity. PEG is electrically neutral at all pH with high active functional terminal and is inert in biological environment. In biomedical applications, PEG confers anti-biofouling effect in-vivo and also improves upon the drug targeting and bioavailability besides anti-biofouling. GO and n-HAP composites were deposited on implant materials along with polymers using various coating techniques. This article focuses on electrophoretic deposition and dip coating techniques which can be used to develop hybrid GO-bioceramic deposits on stainless steels and Ti alloys for orthopedic applications along with study of its corrosion behavior. The obtained hybrid-coated samples have been characterized using atomic force microscopy (AFM), FT-IR, optical microscopy, contact angle, porosity, X-ray diffraction spectroscopy, and electrochemical measurements.Graphical Abstract KeywordsGraphene oxide (GO)Nano-hydroxyapatite (n-HAP)Polyethylene glycol (PEG)Ti alloyElectrophoretic depositionSpin and dip coatingCorrosion resistance

Influence of Extracellular Cues of Hydrogel Biomaterials on Stem Cell Fate

Article

Mar 2022

Tissue engineering is a multidisciplinary field that focuses on creating functional tissue through the combination of biomimetic scaffolds, a cell source, and biochemical/physiochemical cues. Stem cells are often used as the cell source due to their multipotent properties and autologous sourcing; however, the combination of physical and chemical cues that regulate their behavior creates challenges in reproducibly directing them to a specific fate. Hydrogel biomaterials are widely explored as tissue scaffolds due to their innate biomimetic properties and tailorability. For these constructs to be successful, properties such as surface chemistry and spatial configuration, stiffness, and degradability of the biomaterial used for the scaffold framework should be analogous to the natural environment of the tissue they are repairing/replacing. This is imperative, as cues from the surrounding extracellular matrix (ECM) influence stem cell behavior and direct cell differentiation to a specific lineage. Hydrogels offer great promise as tools to control stem cell fate, as researchers can modulate the degradation rates, mechanical properties, swelling behavior, and chemical properties of the biomaterial scaffold to mimic the instructive cues of the native ECM. Discussion of the advantages and challenges of utilizing hydrogel biomaterials as the basis of tissue scaffolds is reviewed herein, as well as specific examples of hydrogels in tissue engineering and advances in hydrogel research to achieve desired cell phenotypes.

Biological applications of green synthesized zinc oxide and nickel oxide nanoparticles mediated poly(glutaric acid-co-ethylene glycol-co-acrylic acid) polymer nanocomposites

Article

Feb 2022
INORG CHEM COMMUN

The metal oxide nanoparticles (NPs), zinc oxide (ZnO) and nickel oxide (NiO) were synthesized using Sterculia foetida (S.foetida) leaf extract by solution combustion method. The Poly(glutaric acid-co-ethylene glycol-co-acrylic acid)(GEA) hydrogel was prepared using three different monomers such as glutaric acid (G), ethylene glycol (E) and acrylic acid (A). The zinc oxide (ZnO) and nickel oxide (NiO) nanoparticles were introduced into GEA hydrogel and the polymer nanocomposites GEA-ZnO and GEA-NiO were obtained. The UV-visible spectroscopy (UV) peak observed at 275 nm and 360 nm for GEA-ZnO and GEA-NiO polymer nanocomposites. The Fourier Transform Infrared (FT-IR) spectral data obtained at 414cm⁻¹ confirmed the presence of nanoparticles in the hydrogel. The size of the nanoparticles were confirmed through Scanning Electron Microscopy (SEM) and Transmission Electron Microscope (TEM) analysis. The size of the zinc oxide nanoparticles (ZnO NPs) introduced in GEA-ZnO polymer nanocomposite was 30 to 35 nm and the size of nickel oxide nanoparticles (NiO NPs) introduced in GEA-NiO nanocomposite was 27 to 33 nm. The percentage of zinc oxide (ZnO) and nickel oxide (NiO) were reported in Energy Dispersive X-ray Analysis (EDAX) spectrum.Where the percentage of zinc (Zn) is 2.22% and nickel (Ni) is 2.7%.The thermal stability of the nanoparticles in the hydrogel was assessed by Thermo gravimetric analysis (TGA). Beyond 450οC there was no change in the Thermo Gravimetric Analysis (TGA) peak of GEA-NiO polymer nanocomposite and found with nil weight loss. The antibacterial activity was performed using Staphylococcus aureus (s.aureus)and Bacillus subtilis (B.subtilis) gram positive bacterial strains and Escherchia coli (E.coli) and Klebsiella pneumoniae (K.pneumoniae) gram negative bacterial strains. The gram positive bacteria showed highest antibacterial activity than gram negative bacteria at highest concentration 100 μg/ml towards polymer nanocomposites.

Structure and pH-Induced Swelling of Polymer Films Prepared from Sequentially Grafted Polyelectrolytes

Article

Full-text available

Jan 2022

We have prepared a series of ampholytic polymer films, using a self-initiated photografting and photopolymerization (SI-PGP) method to sequentially polymerize first anionic (deuterated methacrylic acid (dMAA)) and thereafter cationic (2-aminoethyl methacrylate (AEMA)) monomers to investigate the SI-PGP grafting process. Dry films were investigated by ellipsometry, X-ray, and neutron reflectometry, and their swelling was followed over a pH range from 4.5 to 10.5 with spectroscopic ellipsometry. The deuterated monomer allows us to separate the distributions of the two components by neutron reflectometry. Growth of both polymers proceeds via grafting of solution-polymerized fragments to the surface, and also the second layer is primarily grafted to the substrate and not as a continuation of the existing chains. The polymer films are stratified, with one layer of near 1:1 composition and the other layer enriched in one component and located either above or below the former layer. The ellipsometry results show swelling transitions at low and high pH but with no systematic variation in the pH values where these transitions occur. The results suggest that grafting density in SI-PGP-prepared homopolymers could be increased via repeated polymerization steps, but that this process does not necessarily increase the average chain length.

Syntheses and aggregation properties of new squalene receptors bearing open chain ligands

Article

Dec 2021

New squalene receptors bearing open-chain polyether ligands (SQ-diEG, SQ-triEG, SQ-tetraEG) were synthesised. The stoichiometries and association constants (Ka) for the interactions between these squalene receptors and representative alkaline earth metal ions (Mg²⁺, Ca²⁺, and Ba²⁺) were determined in solution. Fluorescence spectral studies revealed that the squalene receptors self-associate with critical vesicle concentrations at 25 °C of 2.2 × 10⁻⁵ M for SQ-diEG, 2.3 × 10⁻⁵ M for SQ-triEG, and 2.5 × 10⁻⁵ M for SQ-tetraEG. The self-assembly behaviour was probed using laser diffraction particle size-based analyses and scanning electron microscopy. A decrease in the SQ-tetraEG vesicle size was readily induced by the addition of alkaline earth metal ions, confirmed by cryogenic transmission electron microscopy.

Refining of Particulates at Stimuli‐Responsive Interfaces: Label‐Free Sorting and Isolation

Article

Nov 2021

The mechanism of separation methods, e.g. liquid chromatography, is realized through rapid multiple adsorption-desorption steps leading to the dynamic equilibrium state in a mixture of molecules with different partition coefficients. Sorting of colloidal particles, including protein complexes, cells, and viruses, is limited due to a high energy barrier, up to millions kT , required to detach particles from the interface, which is in dramatic contrast to a few kT for small molecules. Such a strong interaction renders particle adsorption quasi-irreversible. The dynamic adsorption-desorption equilibrium is approached very slowly, if ever attainable. This limitation is alleviated with a local oscillating repulsive mechanical force generated at the microstructured stimuli-responsive polymer interface to switch between adsorption and mechanical-force-facilitated desorption of the particles. Such a dynamic regime enables the separation of colloidal mixtures based on the particle-polymer interface affinity, and it could find use in research, diagnostics, and industrial-scale label-free sorting of highly asymmetric mixtures of colloids and cells.

Refining of Particulates at Stimuli‐Responsive Interfaces: Label‐Free Sorting and Isolation

Article

Nov 2021

Insulin smart drug delivery nanoparticles of aminophenylboronic acid–POSS molecule at neutral pH

Article

Full-text available

Nov 2021

Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.

Biodegradable Self-assembled polymeric Micelles based on Poly (ethylene oxide)-block-Polylactide block copolymer for sustained delivery of dapsone

Article

Oct 2021
J DRUG DELIV SCI TEC

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal

Adsorption characteristics and conformational transition of polyethylene glycol–maleated rosin polyesters on the water–air surface

Article

Full-text available

Jun 2022

In this study, three PEG-maleated rosin polyesters were produced by reacting between maleated rosin and PEG with different molecular weights and served as surfactants. The surface characteristics of these PEG-maleated rosin polyesters were detected. The conformational transition and adsorption characteristics of these polyesters were analyzed with the reorientation theory on the water–air surface. The surfactant mole fraction at the water–air surface increased as surfactant concentration increased, while the solvent mole fraction was decreased. The amount of surfactant on the water–air surface at state 1 with a maximal molar area appeared one unimodal in distribution and that at state 2 occupying a minimal molar area appeared a sigmoid distribution with П growth. The calculated adsorption free energy from CMC value is lower than calculated micellization energy obtained from molecular area at state 2 indicates the polyethylene glycol-maleated rosin polyesters firstly spread on the water–air surface and then aggregated into micelles. The results lay a foundation for better understand the adsorption and self-assembly processes. Graphical abstract The adsorption characteristics and conformational transition of three PEG-maleated rosin polyesters were investigated. Paper title: Adsorption Characteristics and Conformational Transition of Polyethylene Glycol-maleated Rosin Polyesters on the Water–Air Surface

Modifying Polydiacetylene Vesicle Compositions to Reduce Non-Specific Interactions

Article

Jul 2021

Polydiacetylene (PDA) vesicles provide useful stimuli-responsive behavior as well as by the modular structure afford a means for the design of sensing and delivery systems with tunable target specificity. To reduce inherent non-specific interaction with either anionic or cationic formulations of polydiacetylene vesicles, we explored the use of various lengths of poly(ethylene glycol) (PEG) amphiphiles for integration and polymerization within PDA vesicles. Our results established that as little as 1% of polyethylene glycol amphiphile integration into anionic vesicles was sufficient to significantly reduce non-specific association with mammalian cells. Similarly integrating a low percent of PEG amphiphile content within cationic vesicles could also significantly reduce non-specific cell association, and moreover reduced cytotoxicity. These results may be prove useful in augmenting PDA vesicles formulations for reduced non-specific interaction which is of particularly interest to enhancing selectivity in vesicles designed with integrated targeting moieties for sensing and drug delivery applications.

Protein Engineering Strategies for Improved Pharmacokinetics

Article

Full-text available

Jun 2021
ADV FUNCT MATER

Protein therapeutics have gained momentum in recent years and become a pillar in treating many diseases and the only choice in several ailments. Protein therapeutics are highly specific, tunable, and less toxic than conventional small drug molecules. However, reaping the full benefits of therapeutic proteins in the clinics is often hindered by issues of immunogenicity and short half‐life due essentially to fast renal clearance and enzymatic degradation. Advances in polymer chemistry and protein engineering allowed overcoming some of these limitations. Strategies to prolong the half‐life of proteins rely on increasing their size and stability and/or fusing them to endogenous proteins (albumin, Fc fragment of antibody) to hijack physiological pathways involved in protein recycling. On the downside, these modifications might alter therapeutic proteins structure and function. Therefore, a compromise between half‐life and activity is sought. This review covers half‐life extension strategies using natural and synthetic polymers as well as fusion to other proteins and sheds light on genetic engineering strategies and chemical and enzymatic reactions to achieve this goal. Promising strategies and successful applications in the clinics are highlighted. In the past decades, breakthroughs in protein engineering strategies have revolutionized the development of long‐acting medicines. Conjugation of polymers, polypeptides, Fc antibody fragments or human serum albumin to a parent therapeutic protein increases its half‐life and modulates protein biological activity.

Synthesis, characterization and surfactant properties of cholic acid containing linear and star polymers

Article

Jul 2021

Surface-active linear and star-shaped miktoarm polymers containing cholic acid as a bile acid derivative are prepared by esterification of poly(ethylene glycol methyl ether) and subsequent ring-opening polymerization of epsilon caprolactone, respectively. The chemical structures, molecular characteristics and thermal properties of obtained polymers are clearly confirmed by FT-IR, 1H-NMR, GPC, DSC and TGA analysis. The presence of characteristic bands of cholic acid, ether and ester groups in FT-IR and 1H-NMR spectroscopies is proof of the successful synthesis of linear and star-shaped polymers. The melting point of star-shaped polymer is slightly lower than the linear polymer. Additionally, their surface activity properties have been investigated by AFM, SEM and contact angle studies and it is found that they can be self-assembled into micelles. Furthermore, the size of the micelles and contact angle properties has been changed with the addition of both hydrophilic (poly(ethylene glycol)) and hydrophobic (poly(epsilon caprolactone)) blocks on the cholic acid head. It is also clearly seen the effect of hydrophobic poly(epsilon caprolactone) functions increased contact angle and surface tension values after the formation of star-shaped polymer.

Enhancing wound healing dressing development through interdisciplinary collaboration

Article

Full-text available

May 2021
J BIOMED MATER RES B

The process of wound healing includes four phases: Hemostasis, inflammation, proliferation, and remodeling. Many wound dressings and technologies have been developed to enhance the body's ability to close wounds and restore the function of damaged tissues. Several advancements in wound healing technology have resulted from innovative experiments by individual scientists or physicians working independently. The interplay between the medical and scientific research fields is vital to translating new discoveries in the lab to treatments at the bedside. Tracing the history of wound dressing development reveals that there is an opportunity for deeper collaboration between multiple disciplines to accelerate the advancement of novel wound healing technologies. In this review, we explore the different types of wound dressings and biomaterials used to treat wounds, and we investigate the role of multidisciplinary collaboration in the development of various wound management technologies to illustrate the benefit of direct collaboration between physicians and scientists.

Analysis of Atomistic Potentials for Poly(ethylene glycol) Ethers

Article

Dec 2020

Two different potentials, the modified TraPPE-UA model of Fischer, J. [ J. Phys. Chem. B 2008, 112, 2388-2398] and the modified general AMBER force-field (GAFF) model of Barbosa, N. S. V. [ J. Mol. Model. 2017, 23, 194]are tested for a variety of temperature-dependent properties for neat and aqueous solutions for small poly(oxyethylene) (PEO) oligomers and larger polymers. A set of charges for PEO of arbitrary size is adapted for the modified GAFF model. Both models accurately reproduce experimental properties, but we find that the modified TraPPE-UA model is more accurate.

Use of Nanoparticulate Systems for Tackling Neurological Aging

Chapter

Oct 2020

In the last chapter, Das and Das have presented the advantages of biodegradable polymeric nanoparticles in biomedical use, and have also provided an overview of general methods of fabricating and designing nanoparticles. In this chapter, we will continue to talk about nanoparticles as carriers of therapeutics, but will narrow down the focus of the discussions to the context of neurological aging. In fact, neurological disorders such as Parkinson’s disease, Alzheimer’s diseases, neuropathic pain, and cerebrovascular accidents affect approximately 1.5 billion people globally. Over the years, an array of bioactive molecules have been found to be effective for the treatment of neurological conditions but not to be clinically effective due to the presence of the blood–brain barrier (BBB). The BBB is primarily responsible for the separation of extracellular fluid and blood within the CNS, generating a selectively permeable barrier restricting the passage of an array of substances, such as drugs, biomolecules, and potentially pathogenic substances. Nanomedicine is an attractive non-invasive technology that can be employed to circumvent this barrier. In this chapter, we will review the current advancements and limitations for the employment of nanomedicine to treat neurological diseases, and will also delineate the clinical and regulatory requirement for market entry of these products.

Construction of His6-Protein A/PEG Co-Immobilized Surface for High-Performance Protein Sensing

Article

Full-text available

Jan 2007

Development of the biointerface for high performance immuno-sensing methods is one of the current research topics in analytical chemistry and biochemistry. We developed histidine-tagged protein A (His6-protein A)/poly(ethylene glycol) (PEG) co-immobilized gold surface as a new class of immuno-sensor chip, where both protein A and PEG are directly immobilized on the surface by the histidine-tag and the thiol group, respectively. In this study, the resulting surface was applied to sandwich assay for specific protein detection based on surface plasmon resonance measurements. Despite the similar content of immobilized antibodies, the amount of secondary antibody on His6-protein A/PEG surface was about eight times higher than that of physically adsorbed antibody/PEG surface. In addition, nonspecific protein absorption was extremely suppressed on His6-protein A/PEG surface, compared with Ni2+ -nitrilotriacetic acid (NTA) surface, which was generally used for the immobilization of histidine-tagged proteins. These results clearly indicate that effective orientation of the immobilized antibody with the prevention of non-specific adsorption was achieved on the His6-protein A/PEG surface.

Using Humidity to Control the Morphology and Properties of Electrospun BioPEGylated Polyhydroxybutyrate Scaffolds

Article

Full-text available

Oct 2020

Electrospinning produces nanofibrous scaffolds with potential for tissue engineering and wound repair. Spinning parameters control scaffold morphology and properties. BioPEGylation of polyhydroxybutyrate (PHB) introduces terminal hydrophilic groups into the hydrophobic chain, making this natural−synthetic hybrid copolymer more susceptible to humidity. Varying the humidity from 10 to 50% RH during electrospinning had a relatively little effect on polyhydroxybutyrate (PHB) average fiber and pore diameters, which remained around 3.0 and 8.7 μm, respectively. In contrast, fiber and pore diameters for electrospun bioPEGylated PHB scaffolds varied significantly with humidity, peaking at 30% RH (5.5 and 14.1 μm, respectively). While scaffolds showed little change, hydrophobicity decreased linearly with humidity during electrospinning. Compared to solvent-cast films, electrospun scaffolds showed significantly greater average cell spread. A 108% increase for olfactory ensheathing cells (OECs) cultivated on bioPEGylated PHB scaffolds was proportionally greater than their counterparts on electrospun PHB scaffolds, (70%). OECS grown on BioPEGylated PHB scaffolds were over twice the size, 260 ± 20 μm diameter, than those on PHB electrospun scaffolds, 110 ± 18 μm diameter. Electrospun scaffolds also promoted cell health compared to their solvent-cast counterparts, with increases in the mitochondrial activity of 165 ± 13 and 196 ± 13% for PHB and bioPEGylated PHB, respectively. OECS cultivated on electrospun scaffolds of bioPEGylated PHB had significantly better membrane integrities compared to their counterparts on solvent-cast films, 47 ± 5% reducing to 17 ± 6%. The combination of bioPEGylation and humidity during electrospinning permitted significant controllable changes to scaffold morphology and properties. These changes resulted in the significantly greater promotion of cell growth on electrospun bioPEGylated PHB scaffolds compared to their solvent-cast counterparts and electrospun PHB.

Eigenschaften von Kunststoffen in Bauteilen

Chapter

Oct 2020

Peter Eyerer

Kap. 3 Band 1 ist, neben Kap. 1 Band 2, das umfangreichste Kapitel dieser 3 Bände. Es beginnt mit dem chemischen, gefolgt vom physikalischen Aufbau der Kunststoffe. Die Bindungsarten leiten das Kapitel ein. Der Zusammenhang zwischen Bindekräften und der mechanischen Festigkeit von Polyethylen schließt die Einführung ab. Die chemische Struktur von Kunststoffen wird ingenieurmäßig erläutert bis hin zum Einbau von Fremdatomen (Copolymerisation) und innere/äußere Weichmachung. Die physikalischen Ordnungszustände (amorph, teilkristallin) sowie die anwendungstechnischen Auswirkungen (Schwindung, Dichte) werden beschrieben. Vernetzte Zustände schließen an. Abschn. 3.2 befasst sich mit der Charakterisierung von Zustandsbereichen in Kunststoffen. Es folgen die Abschn. 3.3 „Mechanische Eigenschaften“, 3.4 „Weitere physikalische Eigenschaften“ und 3.5 „Chemische Eigenschaften“. Abschn. 3.6 dürfte für den Leser wertvoll sein, weil hier Kurzcharakterisierungen von 33 Polymeren abgedruckt sind. Abschn. 3.7 behandelt Zusatzstoffe für Kunststoffe. Abschn. 3.9 behandelt die thermoplastischen Elastomere TPE), gefolgt von den Elastomeren in Abschn. 3.10. Abschn. 3.11 widmet sich den Polysiloxanen. Polymere und Faserverbunde aus natürlichen und synthetischen Rohstoffen (Abschn. 3.15) sowie Duroplaste (Abschn. 3.13) schließen Kap. 3 ab. Kap. 3 wurde umfangreich überarbeitet.

Superoxide dismutase and catalase conjugated to polyethylene glycol increases endothelial enzyme activity and oxidant resistance.

Article

Full-text available

May 1988

Covalent conjugation of superoxide dismutase and catalase with polyethylene glycol (PEG) increases the circulatory half-lives of these enzymes from less than 10 min to 40 h, reduces immunogenicity, and decreases sensitivity to proteolysis. Because PEG has surface active properties and can induce cell fusion, we hypothesized that PEG conjugation could enhance cell binding and association of normally membrane-impermeable enzymes. Incubation of cultured porcine aortic endothelial cells with 125I-PEG-catalase or 125I-PEG-superoxide dismutase produced a linear, concentration-dependent increase in cellular enzyme activity and radioactivity. Fluorescently labeled PEG-superoxide dismutase incubated with endothelial cells showed a vesicular localization. Mechanical injury to cell monolayers, which is known to stimulate endocytosis, further increased the uptake of fluorescent PEG-superoxide dismutase. Endothelial cell cultures incubated with PEG-superoxide dismutase and PEG-catalase for 24 h and then extensively washed were protected from the damaging effects of reactive oxygen species derived from exogenous xanthine oxidase as judged by two criteria: decreased release of intracellular 51Cr-labeled proteins and free radical-induced changes in membrane fluidity, measured by electron paramagnetic resonance spectroscopy of endothelial membrane proteins covalently labeled with 4-maleimido-2,2,6,6-tetramethylpiperidinooxyl. Addition of PEG and PEG-conjugated enzymes perturbed the spin-label binding environment, indicative of producing an increase in plasma membrane fluidity. Thus, PEG conjugation to superoxide dismutase and catalase enhances cell association of these enzymes in a manner which increases cellular enzyme activities and provides prolonged protection from partially reduced oxygen species.

Proton NMR characteristics of polyethylene glycol and derivatives

Article

Full-text available

Aug 1990

Derivatives of poly(ethylene glycol) (PEG) are of importance in a variety of applications. Often it is difficult to determine the identity of the end groups and the purity of these derivatives. In the present work we show that proton NMR spectra of PEGs dissolved in deuterated dimethyl sulfoxide (but not other solvents) reveal a hydroxyl peak at 4.56 (±0.02) ppm, which does not shift or broaden with variation in concentration of the PEG, water, or impurities and which is well separated from the large backbone resonance. The hydroxyl resonance in other solvents does not show this independence, and thus it is difficult to locate and utilize. The PEG hydroxyl resonance for samples in dimethyl sulfoxide is, therefore, well suited for quantifying percent substitution and molecular weight of PEG and derivatives. Use of this method is illustrated.

Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol

Article

Full-text available

Jul 1977

Methoxypolyethylene glycols of 1900 and 5000 daltons have been attached covalently to bovine serum albumin using cyanuric chloride as the coupling agent. When sufficient polymer is attached, the modified bovine serum albumin appears to lose its immunogenicity in the rabbit and, on intramuscular or intravenous injection, elicits antibodies neither to itself nor to native bovine serum albumin. It does not react with antibodies raised against native bovine serum albumin. Bovine serum albumin to which methoxypolyethylene glycol has been attached exhibits a blood circulating life in the rabbit rather similar to native bovine serum albumin, except that it is not removed from circulation by the eventual development of antibodies. Modified bovine serum albumins which had been iodinated with 125I, or prepared with [14C]cyanuric chloride, were injected intravenously in rabbits. Both labels appeared almost quantitatively in the urine after 30 days. The modified bovine serum albumins showed substantial changes in properties, such as solubility, electrophoretic mobility in acrylamide gel, ion exchange chromatography, and sedimentation, as compared with the unmodified protein.

HELP (High Efficiency Liquid Phase) new oligonucleotide synthesis on soluble polymeric support

Article

Full-text available

Jul 1990

A simple, rapid and high-yielding method for the synthesis of oligonucleotides by the phosphotriesters approach Is described. The use of polyethylene glycol (PEG) as soluble polymeric support preserves some convenient features of the solid-phase synthesis with new interesting advantages.Short oligonucleotides in hundred milligrams scale can be obtained from few grams of functionalised PEG.

Chemical modification of recombinant II-2 by polyethylene glycol increases its potency in the murine Meth A sarcoma model

Article

Full-text available

Apr 1987

Recombinant human interleukin 2 purified from Escherichia coli has limited solubility at neutral pH and a short circulatory half-life. This recombinant interleukin 2 was chemically modified by an active ester of polyethylene glycol. The modified interleukin 2 was purified by hydrophobic interaction chromatography and characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and isoelectric focusing. This conjugate was compared to unmodified recombinant interleukin 2 in vitro and in vivo. Covalent attachment of the hydrophilic polymer polyethylene glycol enhanced the solubility of interleukin 2, decreased its plasma clearance, and increased its antitumor potency in the Meth A murine sarcoma model.

Alkylene Oxides and Their Polymers

Book

Jul 2020

Partitioning in Aqueous Two-Phase Systems

Article

Jan 1985

Poly(Ethylene Glycol)s as Phase-Transfer Catalysts Synthesis of Derivatives

Chapter

Jan 1984

Polyethylene glycols (PEG’s) and their derivatives are finding a rapidly expanding range of chemical, biomedical, and industrial applications resulting from their low cost and useful properties such as solubility in aqueous and organic solvents, metal complexing ability, biological compatibility, and ease of chemical modification. The linear polymers have been employed as soluble matrices for liquid-phase peptide synthesis,2 ligands for water-soluble transition metal complexes,3 drug carriers,4 water-soluble cell fusion agents.5 Other reasons for the current interest in PEG’s include their reduction of enzyme immunogenicity,6 and their utility in aqueous two-phase polymer cell separations (phase partitioning).7

Effects of Polyethylene Glycol Substitution on Enzyme Activity

Article

Jan 1987

The effects of polyethylene-glycol (PEG) substitution on protein activity, us ing alkaline phosphatase as a model, have been studied. Such variables as PEG molecular weight, degree of substitution, and PEG mono- and di-functionality have been examined. Modification with the monomethyl ether of PEG 1900 (M- PEG-1900) does not alter enzyme activity until greater than 40% of the protein lysine groups are substituted, at which point increasing the degree of modifica tion gives increasing deactivation. Substitution with M-PEG-5000 gives more deactivation than does substitution with M-PEG-1900. Interestingly, modifica tion with PEG itself gives active protein conjugates in which there is little de pendence on molecular weight or degree of substitution.

Partition of Cell Particles and Macromolecules, Wiley, New York

Book

Jan 1986
TRENDS BIOCHEM SCI

P. Ä. Albertsson

Plant protoplast fusion and growth of intergeneric hybrid cells

Article

Jan 1974
PLANTA

Interspecific and intergeneric fusions of plant protoplasts were induced by polyethylene glycol (PEG) 1540 or 4000. The frequency of heterokaryocyte formation (or rate of fusion) was much higher when PEG was eluted with a high pH-high Ca2+ solution or a salt solution than when it was eluted with a protoplast culture medium. The frequency of heterokaryocyte formation was also affected by the types of enzymes used for wall degradation, duration of enzyme incubation and molality of the PEG solutions. The maximum frequency of heterokaryocyte formation was 23% for V. hajastana Grossh.-soybean (Glycine max L.) and barley (Hordeum vulgare L.)-soybean, 35% for pea (Pisum sativum L.)-soybean, 20% for pea-V. hajastana, 14% for corn (Zea mays L.)-soybean and 10% for V. villosa Roth-V. hajastana. 40% of the barley-soybean, corn-soybean and pea-soybean heterokaryocytes divided at least once. Some divided many times and formed clusters of up to 100 cells in 2 weeks. The heterokaryocytes of soybean-V. hajastana, V. villosa-V. hajastana also divided. Of the PEG-treated protoplasts of N. langsdorffii and N. glauca 13.5% developed into tumor-like calli. The morphology of these calli was very much like that of the tumors produced on amphidiploid plants of N. langsdorffii x glauca. Nuclear staining indicated that heterokaryocytes of V. hajastana-soybean, pea-soybean, corn-soybean and barley-soybean could undergo mitosis. Nuclear divisions in a heterokaryocyte were usually synchronized or almost synchronized. Nuclear fusion and true hybrid formation usually occurred during the first mitotic division after protoplast fusion. A hybrid of barley-soybean in third cell division was observed. The frequency of heterokaryocytes which underwent nuclear fusion has not been determined. Multipole formation and chimeral cell colonies were also observed.

Gel chromatography in eluents containing polymers

Article

Dec 1968
J CHROMATOGR A

Krister Hellsing

In gel chromatographic experiments using Sephadex G-200, human serum albumin has been chromatographed in eluents containing neutral polymers. Each of the four types of polymers studied; dextran, polyethyleneglycol, polyvinylalcohol, and Ficoll, was tested at several concentrations. Albumin is eluted later as the polymer concentration in the eluent is increased. This is ascribed to an activity increase of the protein in the mobile polymer phase that is due mainly to steric exclusion. When the exclusion properties of the gel phase are known one can calculate the exclusion of the test substance from the liquid polymer phase. Measurements made by this method agree well with data derived from solubility studies of the exclusion of albumin from dextran solutions. They agree exactly with the exclusion measurements on dextran gels. The method should be useful in studies of the exclusion properties and the molecular parameters of polymer solutions.

Biochemical Applications of Poly(Ethylene Glycol)

Article

Mar 1980

Irina N. Topchieva

The literature data on the use of poly(ethylene glycol) (PEG) in biochemistry and molecular biology are analysed from the standpoint of the physical chemistry of polymers. The exclusion properties of PEG, used as a factor influencing the rate of enzymatic reactions, the intra- and intermolecular transitions in polymers, and biopolymer precipitation and crystallisation processes are examined. The suitability of three-component PEG–dextran–water mixtures for the purification and separation of mixtures of biopolymers and for analytical purposes as well as the possibility of using functional derivatives of PEG in immunological research and for the immobilisation of enzymes are discussed. A special section is devoted to the synthesis of PEG derivatives containing different functional groups at the ends of the polymer chain. The surface-active properties of PEG are examined. The bibliography includes 78 references.

The Nature of Phase Separation in Aqueous Two-Phase Polymer Systems

Article

Nov 1986
POLYMER

Aqueous systems with two soluble polymers often phase-separate into two isotropic solutions. We investigate the molecular mechanism leading to this phase separation. It is concluded that the important factor is the direct molecular interaction between the monomeric units of two polymers, which should be effectively repulsive for phase separation to occur. Previously it has also been suggested that the size and shape of the entire polymer molecules are important factors, but our analysis does not support this view.

Responses to conjugated AgE in ragweed hay fever

Article

Jan 1962
J ALLERGY CLIN IMMUN

Review : Polyethylene Glycol(PEG)Protein Conjugates: Application to Biomedical and Biotechnological Processes

Article

Jul 1990

Proteins can be modified chemically by attaching synthetic or natural macromolecules to the surface of the protein molecule. In some cases, this manipulation of protein modification with polymers can eliminate some drawbacks of native proteins and improve thier properties. These are important aspects for future application in the use of protein drugs and catalysts in bioreactors. Poly(ethylene glycol) (PEG) with a history of plasma expander, being nonimmunogenic, amphipathic and nontoxic, has been applied to various enzymes as a superior agent for modification. This report is focused on our recent work with poly(ethylene glycol)-protein conjugates and their potential medical aplications.

Effect of d , α-Tocopheryl Succinate and Polyethylene Glycol on Performance Tests After Fluid Percussion Brain Injury

Article

Feb 1989

One hundred and one rats were administered either D, α-tocopheryl succinate plus polyethylene glycol (PEG), PEG, or saline 30 min prior to or 5 min after moderate fluid percussion brain injury. Mortality rates, performance on beam balance and beam-walking tasks, and body weight were assessed daily for 10 days. With preinjury administration, mortality rate was reduced from 31% with saline to 9% with PEG and 9% with D, α-tocopheryl succinate plus PEG. With postinjury administration, mortality rate was reduced from 36% with saline to 20% with PEG and to 10% with the D, α tocopheryl succinate plus PEG combination. With administration prior to injury, PEG and D, α-tocopheryl succinate plus PEG reduced the deficits seen on beam balance testing on days 1-3 after injury. On beam walking, PEG and D, α tocopheryl succinate plus PEG reduced deficits compared to those in saline-injected animals on days 1 and 2 and on day 1 after injury, respectively. A strongly protective effect of PEG and of D, α-tocopheryl succinate plus PEG was seen with preinjury administration. With postinjury administration, D, α-tocopheryl succinate plus PEG reduced deficits on beam balance testing compared to animals receiving both saline and PEG on days 1-3 after injury. On beam-walking latencies, D, α-tocopheryl succinate plus PEG reduced deficits on days 1 and 2 after injury compared to saline and to PEG. Both PEG and D, α-tocopheryl succinate plus PEG reduced weight loss after injury compared to saline. The protective effects of these agents and their relatively low toxicity and high lipid solubility give them potential for the treatment of human head injury.

Phase-Transfer Catalysis

Conference Paper

Jan 1987

C.M. Starks

This book presents papers given at a symposium of the American Chemical Society. Topics covered include: Aromatic substitution in condensation polymerization catalyzed by solid-liquid phase transfer; Triphase catalysis in organometallic anion chemistry; and Multisite phase-transfer catalysts.

Behaviour of Polyethylene Glycol on Dialysis and Gel-filtration

Article

May 1965

A P RYLE

POLYETHYLENE glycol is now widely used for concentrating protein solutions by dialysis. We have used the material of molecular weight 15,000 (L. Light and Co., Ltd., Colnbrook, England) and have found that it penetrates dialysis sacs to an appreciable extent.

Laboratory Synthesis of Polyethylene Glycol Derivatives

Article

Aug 1985

J. Milton Harris

In recent years, derivatives of polyethylene glycol (PEG) have proven valuable in a variety of diverse chemical and biological endeavors. Such applications include peptide synthesis, phase transfer catalysis, pharmaceutical modification, protein and cell purifications, polymer-bound reagents, and binding assays. Because of the great deal of interest surrounding this subject, this review will describe generally applicable laboratory methods for preparing PEG derivatives from the parent PEG. We have largely restricted discussion to this starting material because most research laboratories interested in applications are not equipped to handle complex ethylene oxide polymerizations used in large-scale industrial preparations and because PEG and some of its ethers and esters are the only commonly available polymeric starting materials. For the purpose of this review, PEG is defined as those polyoxyethylenes having hydroxyl endgroups and a molecular weight of 20,000 daltons or less.

Poly(ethylene glycol) ethers as recoverable phase-transfer agents in permanganate oxidations

Article

Feb 1983

Poly(ethylene glycols) as Soluble, Recoverable, Phase-Transfer Catalysts

Article

Mar 1982

Thermodynamic Properties of Aqueous Polymer Solutions: Poly(ethylene glycol)/Dextran

Article

Jul 1989

Vapor pressures at 25°C are reported for binary aqueous solutions containing 5-40 wt % poly(ethylene glycol) (PEG) 3350 or PEG 8000 or Dextran T-70 or Dextan T-500. 'Effective' osmotic second virial coefficients are calculated from vapor-pressure data at concentrations below 15 wt %. These are somewhat larger than second virial coefficients obtained from low-angle laser-light-scattering (LALLS) measurements at high dilution, indicating contributions from higher order interactions. Vapor-pressure data are used together with osmotic second virial coefficients measured by LALLS to fit an 'effective' third virial coefficient for each binary system. Chemical potentials obtained from vapor-pressure and LALLS data are used to predict liquid-liquid equilibria (LLE) for aqueous ternary systems containing PEG and dextran. Predicted and measured LLE are in good agreement.

Thermodynamics of the Partitioning of Biomaterials in Two-Phase Aqueous Polymer Systems: Comparison of Lattice Model to Experimental Data

Article

Mar 1989

The partitionings of five proteins - lysozyme, chymotrypsinogen, ovalbumin, human serum albumin, and bovine serum albumin - in two phase systems made from poly(vinyl methyl ether) (PVME) and poly(ethylene oxide) (PEO) were examined as functions of the compositions of the systems. Chymotrypsinogen partitioning was also examined as a function of PEO molecular weight. Experimental data for the partition coefficients were compared with values calculated from the lattice model of J.N. Baskir et al. Calculations were in good agreement with the experiments over the range of conditions investigated. Estimated phase polymer concentrations near the proteins were generally lower than those in the bulk, indicating that partitioning is primarily governed by steric repulsion of the protein from the phase polymers.

Control of electroosmosis in coated quartz capillaries

Article

Feb 1987

Analytical particle microelectrophoresis was used to evaluate the effectiveness of various coatings for control of the electroosmotic fluid flow that hinders electrophoretic processes. Mobilities of 2-μm-diameter glass and polystyrene latex spheres, exhibiting both negative and zero effective surface charge, were measured in 2-mm-diameter quartz capillaries filled with NaCl solutions within the pH range of 3.5 to 7.8. Covalent coating of capillary inner surfaces with poly(ethylene glycol) caused a reduction in the degree of electroosmotic flow which was related to the poly(ethylene glycol) molecular weight. Poly(ethylene glycol) coatings of 5000 molecular weight, or higher, greatly reduced electroosmosis within the selected pH range, were stable for long periods of time, and appeared to be more effective than dextran, methylcellulose, or silane coatings. Because of these characteristics, poly(ethylene glycol) coatings should be of considerable use for improving various electrophoretic processes as well as in the production of standard particles exhibiting controlled electrophoretic mobilities.

Attachment of drugs to polyethylene glycols

Article

Dec 1983
EUR POLYM J

Polyethylene glycol (PEG) was used as a carrier polymer for the attachment, via end groups, of drugs such as penicillin V, aspirin, amphetamine, quinidine and atropine. For this purpose, methods were developed for the functionalization of PEG; PEG-NH2, PEG-COOH and PEG-NCO were prepared. Use was made of dicyclohexyl carbodiimide together with 4-dimethylamino pyridine or 1-hydroxybenzotriazole for the coupling reactions.

Mechanisms of cell fusion.Nature 253:194-195

Article

Feb 1975

WE report new findings on the chemically-induced fusion of hen erythrocytes and discuss possible ways in which the lipid and protein/glycoprotein components of membranes may behave during the process of membrane fusion. Our observations are consistent with Poste and Allison's1 idea that the aggregation of intrinsic membrane proteins is important in membrane fusion but we suggest that fusion may occur in regions of perturbed lipid bilayer which are thus denuded of intramembranous particles.

Production of mammalian somatic cell hybrids by means of polyethylene glycol

Article

Nov 1975

G Pontecorvo

Polyethylene glycol (PEG) is known to promote fusion of plant protoplasts. Various adaptations of this treatment to mammalian, including human, cell cultures are reported here. PEG is very effective in producing hybrids capable of indefinite multiplication even in cases, such as early passage human skin fibroblasts and lymphocytes, known to be highly recalcitrant to other treatments.

Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: Studies with poly(ethylene glycol)-coated vesicles

Article

Mar 1991
Biochim Biophys Acta

Well-defined liposome systems have previously established the influence of size, surface charge lipid composition and surface ligands, on in vivo fate and behaviour of model compounds entrapped in liposomes. In the present study, preformed liposomes which quantitatively retain aqueous markers were covalenty coupled via dipalmitoylphosphatidyl-ethanolamine, to the hydrophilic polymer, monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating in the presence of plasma, and appear to adsorb plasma components more slowly than liposomes without the polymer, shown using an aqueous two-phase partitioning technique. MPEG-coupled liposomes were cleared from the blood circulation up to 30% more slowly than liposomes without MPEG after intravenous administration to mice, despite the unmodified liposomes being of a composition and size shown previously to favour achievement of maximum half-life. It is suggested that the polymer acts as a surface barrier to plasma factors which otherwise bind to liposomes in the blood and accelerate vesicle removal.

Activity of amphipathic poly(ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target

Article

Mar 1991
Biochim Biophys Acta

Dioleoyl-N-(monomethoxy polyethyleneglycol succinyl)-phosphatidylethanolamine (PEG-PE) (mol. wt. of PEG = 5000), an amphipathic polymer, can be incorporated into the liposome membrane and significantly prolong the blood circulation time of the liposome. As little as 3.7 mol% of PEG-PE in liposome resulted in maximal enhancement of liposome circulation time. However, this activity of PEG-PE was only seen with relatively small liposomes (d less than or equal to 200 nm); larger liposomes containing PEG-PE showed an unusually high level (approx. 35% injected dose) of accumulation in the spleen. We have tested whether the small, PEG-PE containing liposomes are suitable for immuno targeting by incorporating a lung-specific monoclonal antibody on the liposome surface. While another amphiphile, ganglioside GM1, which is well known for its activity to prolong the liposome circulation time, significantly enhanced the lung binding of the immunoliposomes, PEG-PE incorporation of immunoliposomes resulted in a low level of target binding. To test if the reduced target binding is due to a steric barrier effect of the surface PEG polymer, we have incorporated a small amount of N-biotinaminocaproylphosphatidylethanolamine into the PEG-PE containing liposomes and examined the liposome agglutination induced by the addition of streptavidin. As little as 0.72 mol% PEG-PE in these liposomes completely abolished agglutination. In contrast, incorporation of GM1 in liposomes only reduced the rate, but not the extent, of liposome agglutination. These results strongly support the hypothesis that PEG-PE prolongs liposome circulation time by providing a strong steric barrier which prevents close contact with another liposome or cell. Since GM1 provides only a weak steric barrier effect, its activity to prolong the liposome circulation time must involve another yet unknown mechanism.

Rapid morphological fusion of severed myelinated axons by polyethylene glycol

Article

Mar 1990

We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye between apposed MGA segments fused with PEG, but not between apposed MGA segments in normal or hypotonic saline without PEG application. PEG-induced MGA fusion rates can be as high as 80-100% with an appropriate choice of PEG concentration and molecular mass, tight apposition and careful alignment of the cut ends, and treatment with hypotonic salines containing reduced calcium and increased magnesium. A variant of this technique might produce rapid repair of severed mammalian-myelinated axons.

Deformation and instability in membrane structure of phospholipid vesicles caused by osmophobic association: Mechanical stress model for the mechanism of poly(ethylene glycol)-induced membrane fusion

Article

Feb 1990

The mechanism of poly(ethylene glycol)-induced fusion of phospholipid vesicles was studied based on the "osmophobic association" theory which was recently proposed both theoretically [Ito, T., Yamazaki, M., & Ohnishi, S. (1989) Biochemistry 28, 5626-5630] and also experimentally [Yamazaki, M., Ohnishi, S., & Ito, T. (1989) Biochemistry 28, 3710-3715]. Osmophobic association and fusion were detected by measuring the light scattering of the vesicle suspension; the former was detected from the increase in light scattering induced by the addition of PEG, and the latter was from the irreversibility of the increase in light scattering. Threshold concentrations of PEG were required not only for osmophobic association but also for fusion. The threshold concentration for fusion depended on the molecular weight of PEG and also on the electrostatic repulsive interaction between phospholipid vesicles, which was manipulated by the use of vesicles with negative surface charge; increasing the molecular weight of PEG lowered the threshold concentration, and increasing the electrostatic repulsive interaction raised it. In addition, a transient leakage of internal contents from the vesicles was observed at the concentration that caused fusion. When the surface charge of the vesicle was varied, the threshold for fusion coincided with that for osmophobic association, provided that the latter exceeded 22 wt % of PEG 6000. However, when the threshold for osmophobic association was less than 22 wt %, the threshold for fusion remained approximately 22 wt %, irrespective of the difference in the threshold for osmophobic association.(ABSTRACT TRUNCATED AT 250 WORDS)

New phase supports for liquid-liquid partition chromatography of bio-polymers in aqueous poly(ethyleneglycol)-dextran systems—Synthesis and application for the fractionation of DNA restriction fragments

Article

Mar 1986

Werner MÜLLER

New phase supports for liquid-liquid partition chromatography, using aqueous poly(ethyleneglycol)-dextran systems have been developed by grafting linear polyacrylamide chains on to premanufactured chromatographic supports carrying primary or secondary aliphatic hydroxyl functions on their surface. Columns prepared from such supports have a higher binding capacity for the dextran-rich stationary phase and much higher performances than columns prepared from cellulose, the previously used phase support for this system. Test separations of DNA restriction fragments, ranging from 11 base pairs to 3829 base pairs, document a high resolution for DNA fragments larger than 200 base pairs.

Evaluation of monomethoxypolyethylene glycol derivatized superoxide dismutase in blood and evidence for its binding to blood cells

Article

Jul 1989
Il Farmaco

A method to evaluate in blood free superoxide dismutase (SOD) and SOD covalently bound to monomethoxypolyethylene glycol (MPEG-5000) is reported. The method takes advantage of gel filtration and cationic exchange chromatography to remove substances present in plasma which can interfere with the SOD enzymatic assay. Using this methodology, it was demonstrated that, contrary to free SOD, MPEG-SOD, when added to blood, was not completely recovered in plasma. Binding of MPEG-SOD to blood cell components takes place involving interactions of MPEG chains with cell membranes.

Oxidation of polyethylene glycols by alcohol dehydrogenase

Article

Feb 1989
BIOCHEM PHARMACOL

The present studies were undertaken to investigate the enzymology of a fatal toxic syndrome that resulted from the absorption and subsequent oxidation of polyethylene glycol (PEG). The presence of organic acids of PEG in the blood of poisoned patients and in an animal model suggested that the metabolism of PEG involved sequential oxidations by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. A key question concerned the ability of ADH to initiate this pathway for oxidation of PEG. In the present studies the oxidation of PEG homologues by ADH was characterized. The polymer homologues of ethylene glycol from n = 1 to n = 8 were used as substrates. ADH catalyzed the oxidation of each of these PEGs. The oxidation of PEG was inhibited by the ADH inhibitor 4-methylpyrazole. With the exception of diethylene glycol, the Km decreased as the homologue number increased, and the Vmax decreased progressively through the series. The concentrations of PEG in the blood of poisoned humans and animals were 0.06 to 0.8 Km of ADH for all the PEG homologues above the triethylene glycol. These investigations establish ADH as a candidate enzyme for mammalian metabolism of PEG and thus suggest that specific inhibitors of ADH may prove to be useful as tools to treat PEG poisoning.

The fusogenic substance dimethyl sulfoxide enhances exocytosis in motor nerve endings

Article

Nov 1985
Biochim Biophys Acta

Fusion of synaptic vesicles with the surface membrane of the nerve terminal is a key step in synaptic transmission, which normally requires the entry of calcium ions into the cell. We report that this fusion and the subsequent liberation of transmitter can also be induced by the fusogenic substances DMSO (dimethyl sulfoxide) and PEG (poly(ethylene glycol)). Calcium ions and DMSO exhibit a synergistic effect in the fusion of synaptic vesicles with the axolemma, resembling their action on fusion phenomena in liposomes.

Cell separation by immunoaffinity partitioning with polyethylene glycol-modified protein A in aqueous polymer two-phase systems

Article

Jul 1988
J CHROMATOGR A

Previous work has shown that polyethylene glycol (PEG)-bound antibodies can be used as affinity ligands in PEG-dextran two-phase systems to provide selective partitioning of cells to the PEG-rich phase. In the present work we show that immunoaffinity partitioning can be simplified by use of PEG-modified Protein A which complexes with unmodified antibody and cells and shifts their partitioning into the PEG-rich phase, thus eliminating the need to prepare a PEG-modified antibody for each cell type. In addition, we provide a more rigorous test of the original technique with PEG-bound antibodies by showing that it is effective at shifting the partitioning of either cell type of a mixture of two cell populations.

Reconnection of severed nerve axons with polyethylene glycol

Article

Apr 1986
BRAIN RES

Severed medial giant axons in crayfish can be rejoined in vitro with polyethylene glycol (PEG) to produce axoplasmic continuity and through transmission of action potentials. Severed axon-like processes of a mammalian neuroblastoma/glioma cell line seem to be rejoined to the cell body using PEG in tissue culture. Our data suggest that PEG might be used to rejoin severed axons in vivo in various organisms.

Treatment of Adenosine Deaminase Deficiency with Polyethylene Glycol–Modified Adenosine Deaminase

Article

Apr 1987

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.

Use of Water-Soluble Polymers for the Isolation and Purification of Human Immunoglobulins

Article

Jul 1967

By the use of fractional precipitation with high molecular weight nonionic polymers, immune globulins of marked homogeneity were isolated in high yield from either whole serum or commercial samples of immunoglobulins. The isolated fractions were characterized by immunochemical and ultracentrifugal analyses. When the pH was varied from 4.9 to 8.6 and the ionic strength from 0.1 to 2.0, little effect on the precipitation of the immunoglobulins was noted. The immunochemical studies indicated that this fractionation technique is not effective in separating the γG, γM, and γA activities present in the γ-globulins isolated from whole serum or in commercial immunoglobulin preparations.Preliminary experiments indicate that this technique may be used for the isolation of other serum proteins, especially albumin and the α-globulins. In these instances, however, it is important that ionic strength and pH be controlled.The mechanism for the precipitation of serum proteins by PEG has not been established, but it is suggested that the precipitation involves a local dehydration and consequent change in the dielectric constant of the medium immediately surrounding the protein molecules.It would appear that the high-polymer precipitation technique may be an effective and simple method for the isolation of serum proteins with preservation of much of their native properties.

Clinical Investigation of Intermediate- and High-Purity Antihaemophilic Factor (Factor VIII) Concentrates

Article

Aug 1971

. Intermediate- and high-purity antibaemophilic factor (factor-VIII) concentrates developed by the American National Red Cross (ANRC) have undergone extensive clinical investigation. When administered to severely affected haemophiliacs, the recovery in vivo and the metabolic half-disappearance time were similar to those achieved with plasma.

Antibodies against Polyethylene Glycol Produced in Animals by Immunization with Monomethoxy Polyethylene Glycol Modified Proteins

Article

Feb 1983

Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD), and ragweed pollen extract (Rag), given in Freund's complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c., did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of MW 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of MW 5.9 X 10(6), given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of MW greater than or equal to 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of MW 300 it appears that the antigenic determinant of PEG may be a sequence of 6-7 -CH2CH2O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1-1 microgram/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.

Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates

Article

Jul 1984
Canc Biochem Biophys

The covalent attachment of monomethoxypolyethylene glycol (PEG) to asparaginases from Escherichia coli and Vibrio succinogenes by new coupling methodology produced conjugates that are active, stable, without significant immune response, and with greatly extended plasma half-lives in mice. Therapeutic efficacies were greater for the PEG-asparaginases than for the unmodified asparaginases in mice infected with the L5178Y lymphosarcoma or the 6C3HED tumor. Large single doses of native or modified enzymes were more effective against tumors than the same amount of enzyme given in smaller doses over several days.

Aggregation and fusion of unilamellar vesicles by poly(ethylene glycol)

Article

Oct 1984
Biochim Biophys Acta

Various aspects of the interaction between the fusogen, poly(ethylene glycol) and phospholipids were examined. The aggregation and fusion of small unilamellar vesicles of egg phosphatidylcholine (PC), bovine brain phosphatidylserine (PS) and dimyristoylphosphatidylcholine (DMPC) were studied by dynamic light scattering, electron microscopy and NMR. The fusion efficiency of Dextran, glycerol, sucrose and poly(ethylene glycol) of different molecular weights were compared. Lower molecular weight poly(ethylene glycol) are less efficient with respect to both aggregation and fusion. The purity of poly(ethylene glycol) does not affect its fusion efficiency. Dehydrating agents, such as Dextran, glycerol and sucrose, do not induce fusion. 31P-NMR results revealed a restriction in the phospholipid motion by poly(ethylene glycol) greater than that by glycerol and Dextran of similar viscosity and dehydrating capacity. This may be associated with the binding of poly(ethylene glycol) to egg PC, with a binding capacity of 1 mol of poly(ethylene glycol) to 12 mol of lipid. Fusion is greatly enhanced below the phase transition for DMPC, with extensive fusion occurring below 6% poly(ethylene glycol). Fusion of PS small unilamellar vesicles depends critically on the presence of cations. Large unilamellar vesicles were found to fuse less readily than small unilamellar vesicles. The results suggest that defects in the bilayer plays an important role in membrane fusion, and the 'rigidization' of the phospholipid molecules facilitates fusion possibly through the creation of defects along domain boundaries. Vesicle aggregation caused by dehydration and surface charge neutralization is a necessary but not a sufficient condition for fusion.

Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications

Abstract

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