Oligo Ethylene Glycol Research Articles

Synthesis and characterization of bile acid‐based polymeric micelle as a drug carrier for doxorubicin

AbstractIn the present study, a polymeric micelle based on amphiphilic block copolymer, namely poly(methacrylated methyl lithocholate)‐block‐poly(oligoethylene glycol methacrylate) (PMML‐b‐POEGMA) bearing bile acid moiety is prepared via sequential photo‐initiated free radical polymerizations, and its drug carrying capacity is investigated using doxorubicin hydrochloride (DOX) as a model drug. For this purpose, two‐step procedure is applied in the presence of phenylbis (2,4,6‐trimethylbenzoyl)phosphine oxide (BAPO) as bifunctional photo initiator. Based on spectroscopic and chromatographic analyses, the desired amphiphilic block copolymer (PMML‐b‐POEGMA) is successfully synthesized by wavelength‐selective free radical photopolymerization under mild conditions. Finally, the DOX drug is loaded into the PMML‐b‐POEGMA micelles and then drug release behavior is investigated at two different pH (5.5 and 7.4) values. It is concluded from the results that PMML‐b‐POEGMA micelles may be used as an efficient nanocarrier to deliver conventional anti‐cancer drugs for combination chemotherapy.

Thermoresponsive Copolymer Nanovectors Improve the Bioavailability of Retrograde Inhibitors in the Treatment of Leishmania Infections

Clinical manifestations of leishmaniasis range from self-healing, cutaneous lesions to fatal infections of the viscera. With no preventative Leishmania vaccine available, the frontline option against leishmaniasis is chemotherapy. Unfortunately, currently available anti-Leishmania drugs face several obstacles, including toxicity that limits dosing and emergent drug resistant strains in endemic regions. It is, therefore, imperative that more effective drug formulations with decreased toxicity profiles are developed. Previous studies had shown that 2-(((5-Methyl-2-thienyl)methylene)amino)-N-phenylbenzamide (also called Retro-2) has efficacy against Leishmania infections. Structure–activity relationship (SAR) analogs of Retro-2, using the dihydroquinazolinone (DHQZ) base structure, were subsequently described that are more efficacious than Retro-2. However, considering the hydrophobic nature of these compounds that limits their solubility and uptake, the current studies were initiated to determine whether the solubility of Retro-2 and its SAR analogs could be enhanced through encapsulation in amphiphilic polymer nanoparticles. We evaluated encapsulation of these compounds in the amphiphilic, thermoresponsive oligo(ethylene glycol) methacrylate-co-pentafluorostyrene (PFG30) copolymer that forms nanoparticle aggregates upon heating past temperatures of 30°C. The hydrophobic tracer, coumarin 6, was used to evaluate uptake of a hydrophobic molecule into PFG30 aggregates. Mass spectrometry analysis showed considerably greater delivery of encapsulated DHQZ analogs into infected cells and more rapid shrinkage of L. amazonensis communal vacuoles. Moreover, encapsulation in PFG30 augmented the efficacy of Retro-2 and its SAR analogs to clear both L. amazonensis and L. donovani infections. These studies demonstrate that encapsulation of compounds in PFG30 is a viable approach to dramatically increase bioavailability and efficacy of anti-Leishmania compounds.

Asymmetric Glycolated Substitution for Enhanced Permittivity and Ecocompatibility of High-Performance Photovoltaic Electron Acceptor.

Traditional organic photovoltaic materials exhibit low dielectric constants (εr) of 3 to 4, restricting the further enhancement of power conversion efficiencies (PCEs) of organic solar cells (OSCs). Herein we design and synthesize a fused-ring electron acceptor named Y6-4O through introducing an asymmetric highly polarizable oligo(ethylene glycol) side chain onto the pyrrole unit of Y6. Compared with alkylated Y6 (εr = 3.36), asymmetric glycolated Y6-4O shows a notably higher εr value of 5.13 and better solubility in nonhalogen solvents. Because of the higher εr value, the devices based on as-cast PM6:Y6-4O processed using toluene exhibit a higher charge separation yield, slower bimolecular recombination kinetics, and less voltage loss relative to the control devices based on PM6:Y6. Consequently, a high PCE of 15.2% is achieved for PM6:Y6-4O-based devices, whereas the PM6:Y6-based devices show PCEs of only 7.38%. 15.2% is the highest PCE for the as-cast nonhalogenated processed OSC devices, and it is also much higher than the values (<8.5%) reported for OSCs based on high-permittivity (εr > 5) organic photovoltaic semiconductors.

Modulating the Thermoresponse of Polymer-Protein Conjugates with Hydrogels for Controlled Release.

Sustained release is being explored to increase plasma and tissue residence times of polymer-protein therapeutics for improved efficacy. Recently, poly(oligo(ethylene glycol) methyl ether methacrylate) (PEGMA) polymers have been established as potential PEG alternatives to further decrease immunogenicity and introduce responsive or sieving properties. We developed a drug delivery system that locally depresses the lower critical solution temperature (LCST) of PEGMA-protein conjugates within zwitterionic hydrogels for controlled release. Inside the hydrogel the conjugates partially aggregate through PEGMA-PEGMA chain interactions to limit their release rates, whereas conjugates outside of the hydrogel are completely solubilized. Release can therefore be tuned by altering hydrogel components and the PEGMA’s temperature sensitivity without the need for traditional controlled release mechanisms such as particle encapsulation or affinity interactions. Combining local LCST depression technology and degradable zwitterionic hydrogels, complete release of the conjugate was achieved over 13 days.

Conformation, Self-Organization and Thermoresponsibility of Polymethacrylate Molecular Brushes with Oligo(ethylene glycol)-block-oligo(propylene glycol) Side Chains.

Polymethacrylic molecular brushes with oligo(ethylene glycol)-block-oligo(propylene glycol) side chains were investigated by static and dynamic light scattering and viscometry. The solvents used were acetonitrile, tetrahydrofuran, chloroform, and water. The grafted copolymers were molecularly dispersed and dissolved in tetrahydrofuran and acetonitrile. In these solvents, the molar masses of copolymers were determined. In thermodynamically good solvents, namely tetrahydrofuran and acetonitrile, investigated copolymers have a high intramolecular density and the shape of their molecules resembles a star-shaped macromolecule. In chloroform and water, the micelle-like aggregates were formed. Critical micelle concentrations decreased with the lengthening of the hydrophobic block. Molecular brushes demonstrated thermosensitive behavior in aqueous solutions. The phase separation temperatures reduced with an increase in the content of the oligo(propylene glycol) block.

Modification and Patterning of Self‐Assembled Monolayers Using Electrogenerated Etchants and Homogeneous Scavenging Reactions in a Scanning Electrochemical Microscope

AbstractSelf‐assembled monolayers (SAMs) of oligoethylene glycol (OEG)‐terminated alkanethiolates on gold, which are used to control protein adsorption and cell adhesion, were patterned by reaction with Br2/HOBr electrogenerated at a microelectrode of a scanning electrochemical microscope (SECM). The spreading of the Br2 diffusion layers was limited by a homogeneous reaction with cystamine or L‐cystine as scavengers. The influence of process parameters on the patterning process was explored by simulation and combinatorial experiments. The experimental determination of pattern sizes from SECM feedback images was verified by scanning force microscopy. The simulation considered the local Br2 formation as well as Br2 consumption in the reaction with the OEG SAM, by reduction at the gold substrate, and by the homogeneous scavenging reaction. It used experimentally determined diffusion coefficients and rate constants of the scavenging reaction. and Experiments and simulation confirmed the existence of regions in the parameter space, in which the patterning process is robust against small variation of the parameters working distance, pulse time and scavenger excess.

Recent Advances in Molecular Design of Organic Thermoelectric Materials

Recent Advances in Molecular Design of Organic Thermoelectric Materials

Vesicle Formation by the Self-Assembly of Gold Nanoparticles Covered with Fluorinated Oligo(ethylene glycol)-Terminated Ligands and Its Stability in Aqueous Solution.

Water-stable gold nanoparticle vesicles (GNVs) with hollow interiors have attracted attention due to their great potential for biological applications; however, their preparation through the self-assembly approaches has been restricted due to the limited understanding of their critical mechanistic issues. In this paper, we demonstrate that a fluorinated tetra (ethylene glycol) (FTEG)-terminated tetra (ethylene glycol) (EG4), namely, FTEG-EG4, ligand can self-assemble with gold nanoparticles (5 and 10 nm) into GNVs with a hollow structure in THF due to the solvophobic feature of the ligand. Time-dependent studies showed that the GNVs with a closely packed surface derived from the incomplete and irregular GNVs, but not through the fusion of the GNV precursors. After dialysis in water, the assemblies retained vesicular structures in water, even though GNVs aggregated together, which was initiated by the hydrophobic interactions between the FTEG heads of the surface ligands on GNVs. This study provides a new insight into the design of novel small surface ligands to produce water-stable GNVs for biological applications.

Homopolymer and ABC Triblock Copolymer Mixtures for Thermoresponsive Gel Formulations.

Our group has recently invented a novel series of thermoresponsive ABC triblock terpolymers based on oligo(ethylene glycol) methyl ether methacrylate with average Mn 300 g mol−1 (OEGMA300, A unit), n-butyl methacrylate (BuMA, B unit) and di(ethylene glycol) methyl ether methacrylate (DEGMA, C unit) with excellent thermogelling properties. In this study, we investigate how the addition of OEGMA300x homopolymers of varying molar mass (MM) affects the gelation characteristics of the best performing ABC triblock terpolymer. Interestingly, the gelation is not disrupted by the addition of the homopolymers, with the gelation temperature (Tgel) remaining stable at around 30 °C, depending on the MM and content in OEGMA300x homopolymer. Moreover, stronger gels are formed when higher MM OEGMA300x homopolymers are added, presumably due to the homopolymer chains acting as bridges between the micelles formed by the triblock terpolymer, thus, favouring gelation. In summary, novel formulations based on mixtures of triblock copolymer and homopolymers are presented, which can provide a cost-effective alternative for use in biomedical applications, compared to the use of the triblock copolymer only.

Switchable [formula omitted]-lactoglobulin (BLG) adsorption on protein resistant oligo (ethylene glycol) (OEG) self-assembled monolayers (SAMs)

HypothesisAlthough protein adsorption at an interface is very common and important in biology and biotechnology, it is still not fully understood – mainly due to the intricate balance of forces that ultimately control it. In food processing (and medicine), controlling and manipulating protein adsorption, as well as avoiding protein adsorption (biofilm formation or membrane fouling) by the production of protein-resistant surfaces is of substantial interest. A major factor conferring resistance towards protein adsorption to a surface is the presence of tightly bound water molecules, as is the case in oligo ethylene glycol (OEG)-terminated self-assembled monolayers (SAMs). Due to strong attractive protein-protein and protein-surface interactions observed in systems containing trivalent salt ions, we hypothesize that these conditions may lead to a breakdown of protein resistance in OEG SAMs. ExperimentsWe studied the adsorption behavior of BLG in the presence of a lanthanum(III) chloride (LaCl3) at concentrations of 0, 0.1, 0.8 and 5.0 mM on normally protein resistant triethylene glycol-termianted (EG3) SAMs on a gold surface. We used quartz-crystal microbalance with dissipation (QCM-D) and neutron reflectivity (NR) to characterize the morphology of the interfacial region of the SAM. FindingsWe demonstrate that the protein resistance of the EG3 SAM breaks down beyond a threshold salt concentration c∗ and mirrors the bulk behaviour of this system, showing reduced adsorption beyond a second critical salt concentration c∗∗. These results demonstrate for the first time the controlled switching of the protein-resistant properties of this type of SAM by the addition of trivalent salt.

Honokiol-Based Nanomedicine Decorated with Ethylene Glycols Derivatives Promotes Antitumor Efficacy.

Honokiol-loaded nanoparticles (HK-loaded NPs) exhibit potential antitumor activity; however, the factors affecting their antitumor efficacy are still unclear and need to be explored. This research was aimed to systematically estimate the influence of feed weight ratio (FWR) and nanocarrier structure on antitumor activity. Accordingly, three types of ethylene glycol derivatives, including linear poly(ethylene glycol) with molar mass of 2000 (PEG45), first and second generation oligo(ethylene glycol) dendrons (G1 and G2) were used as nanocarriers, and a series of HK-loaded NPs with different FWR were prepared successfully using the evaporation-ultrasonication method. These NPs showed similar stability but demonstrated differences with respect to particle size, morphology, cumulative profile, and antitumor efficacy. The influence of the FWR was studied using G1 dendrons as nanocarriers; the results indicated that the particle size and morphology of G1 NPs were significantly affected, and G1 NPs (8/1), with the FWR of 8/1 for HK versus G1 dendron, exhibited the highest antitumor activity among all G1 NPs. Furthermore, the influence of nanocarrier structure was investigated at the FWR of 4/1; the findings revealed reduction in the particle diameter from 280 nm to 109 nm and change in morphology from sphere to flower-like structure with an increase in the branch degree from linear to dendron. Moreover, G2 NPs (4/1), with the FWR of 4/1 for HK versus G2 dendron, carrying the highest branch degree exhibited the greatest antitumor efficacy among all. These results are suggestive of influence of particle size and morphology on antitumor efficacy of HK-loaded NPs. Conclusively, this study demonstrated nanocarrier structure and the FWR significantly affect the antitumor efficacy of NPs, which should be optimized for designing nanoscale delivery systems.

Molecular protectors: Superheroes for nanostructures

Molecular protectors: Superheroes for nanostructures

Guanidinium-Responsive Crown Ether-Based Macrocyclic Amphiphile in Aqueous Medium.

Supramolecular assemblies based on oligo(ethylene glycol) (OEG) building blocks are well-known for their neutral chemical property and thermal-responsive behavior. Here, the cyclic "CLOSED" and linear "OPEN" typologies of OEGs led to dramatic difference in the sensitivity to guanidinium-containing species. From thermodynamic studies, the association constant (Ka) between the "CLOSED" form amphiphile and guanidinium salt was determined to be 28.7 M-1, whereas there was no detectable binding affinity for the "OPEN" form. Therefore, considering ion specificity, the present results establish that crown ether derivatives with "CLOSED" and "OPEN" topologies provide an easy-to-access model pair with designed ion-recognition sites and special functional moieties and geometries (like the binding pockets of enzymes or ion channels in cellular members) that allow the manipulation of the intercrossed relationship between supramolecular solutes, waters, and guanidinium salts. These supramolecular forces in aqueous solution offered an alternative strategy to fabricate thermal-responsive systems in ionic medium.

ThermosensitivePMMAcore/oligo(ethylene glycol)‐based shell microgels as drug carriers in detoxification treatment

AbstractThe core‐shell structured polymer microgels were synthesized by coating the hydrophobic poly(methyl methacrylate) (PMMA) sphere cores with hydrophilic nonlinear poly(ethylene glycol)‐based gel shell layer. The uniqueness of these core‐shell microgels lies in the integration of the PMMA core microsphere with strong hydrophobicity and the novel oligo(ethylene glycol)‐based gel layer with well‐defined thermosensitivity for improving loading/release efficacy of two detoxification drugs (chlorpromazine and diltiazem). The hydrophilic shell is composed of hydrophilic copolymer of 2‐(2‐methoxyethoxy)ethyl methacrylate (MEO2MA) with oligo(ethylene glycol) methyl ether methacrylates (MEO5MA). It was found that the molar ratio of two shell monomersn(MEO2MA)/n(MEO5MA) of 1:6 was an ideal matching value for production of the P(MEO2MA)/P(MEO2MA‐co‐MEO5MA) core‐shell microgels with tunable volume phase transition temperature and excellent colloidal stability across the physiologically important temperature range. Moreover, chlorpromazine‐ and diltiazem‐loaded microgels can show an obvious thermosensitive release and in vitro sustained‐release characteristic up to 80 h.

Sticky Hydrogels from Hydrazide-Functionalized Poly(oligo(ethylene glycol) methacrylate) and Dialdehyde Cellulose Nanocrystals with Tunable Thermal and Strain-Hardening Characteristics

Sticky Hydrogels from Hydrazide-Functionalized Poly(oligo(ethylene glycol) methacrylate) and Dialdehyde Cellulose Nanocrystals with Tunable Thermal and Strain-Hardening Characteristics

Influence of Charge Fraction on the Phase Behavior of Symmetric Single-Ion Conducting Diblock Copolymers.

A series of symmetric poly[(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) propyl sodium sulfonate methacrylate)]-block-polystyrene (PsOEGMA-PS) diblock copolymers were synthesized as a model system to probe the effect of charge fraction on the phase behavior of charged-neutral single-ion conducting diblock copolymers. Small-angle X-ray scattering (SAXS) experiments showed that increasing the charge fraction does not alter the ordered phase morphology (lamellar) but increases the order-disorder transition temperature (TODT) significantly. Additionally, the effective Flory-Huggins interaction parameter (χeff) was found to increase linearly with the charge fraction, similar to the case of conventional salt-doped diblock copolymers. This indicates that the effect of counterion solvation, attributed to the significant mismatch between the dielectric constant of each block, provides the dominant effect in tuning the phase behavior of this charged diblock copolymer. We therefore infer that electrostatic cohesion (local charge ordering induced by Coulombic interactions), which is predicted to suppress microphase separation and lead to asymmetric phase diagrams, only plays a minor role in this model system.

Electron Transport Layers Based on Oligo(ethylene glycol)-Incorporated Polymers Enabling Reproducible Fabrication of High-Performance Organic Solar Cells

Interlayers in organic solar cells (OSCs) play a crucial role in determining their charge extraction properties, device performance, and stability. In this work, two naphthalene diimide (NDI)-based n-type polymers (P(NDIDEG-T) and P(NDITEG-T)) incorporating oligo(ethylene glycol) (OEG) side chains of different lengths are designed and used as new electron transport layers (ETLs) in OSCs. The hydrophilic OEG side chains enable the processing of these n-type polymers using eco-friendly water/ethanol mixtures. In addition, the polar OEG groups effectively modify the work function of the Ag cathode, enabling the polymers to function as efficient ETLs. Consequently, when these OEG-based ETLs are applied to PM6:Y6-based OSCs, a maximum power conversion efficiency (PCE) of 15.43% is achieved, which is substantially higher than that of a reference OSC without an ETL (9.93%) and comparable to that of an OSC with a representative high-performance PFN-Br ETL (15.34%). We demonstrate that the P(NDIDEG-T)-based OSCs show both enhanced PCEs and better reproducibility than their P(NDITEG-T)-based counterparts, which are attributed to the lower surface tension and improved film uniformity of the P(NDIDEG-T) ETL. Also, the P(NDIDEG-T) ETL realizes OSCs with higher storage stability and more thickness-tolerant performance compared to the P(NDITEG-T) and PFN-Br ETLs. Our study provides useful guidelines for the design of ETLs suitable for the fabrication of high-performance, reproducible, and stable OSCs.

Designing Nonfullerene Acceptors with Oligo(Ethylene Glycol) Side Chains: Unraveling the Origin of Increased Open-Circuit Voltage and Balanced Charge Carrier Mobilities.

Despite the recent rapid development of organic solar cells (OSCs), the low dielectric constant (ϵr =3-4) of organic semiconducting materials limits their performance lower than inorganic and perovskite solar cells. In this work, we introduce oligo(ethylene glycol) (OEG) side chains into the dicyanodistyrylbenzene-based non-fullerene acceptors (NIDCS) to increase its ϵr up to 5.4. In particular, a NIDCS acceptor bearing two triethylene glycol chains (NIDCS-EO3) shows VOC as high as 1.12 V in an OSC device with a polymer donor PTB7, which is attributed to reduced exciton binding energy of the blend film. Also, the larger size grain formation with well-ordered stacking structure of the NIDCS-EO3 blend film leads to the increased charge mobility and thus to the improved charge mobility balance, resulting in higher JSC , FF, and PCE in the OSC device compared to those of a device using the hexyl chain-based NIDCS acceptor (NIDCS-HO). Finally, we fabricate NIDCS-EO3 devices with various commercial donors including P3HT, DTS-F, and PCE11 to show higher photovoltaic performance than the NIDCS-HO devices, suggesting versatility of NIDCS-EO3.

Nanostructural Characterization of Cardiolipin-Containing Tethered Lipid Bilayers Adsorbed on Gold and Silicon Substrates for Protein Incorporation

A key to the development of lipid membrane-based devices is a fundamental understanding of how the molecular structure of the lipid bilayer membrane is influenced by the type of lipids used to build the membrane. This is particularly important when membrane proteins are included in these devices since the precise lipid environment affects the ability to incorporate membrane proteins and their functionality. Here, we used neutron reflectometry to investigate the structure of tethered bilayer lipid membranes and to characterize the incorporation of the NhaA sodium proton exchanger in the bilayer. The lipid membranes were composed of two lipids, dioleoyl phosphatidylcholine and cardiolipin, and were adsorbed on gold and silicon substrates using two different tethering architectures based on functionalized oligoethylene glycol molecules of different lengths. In all of the investigated samples, the addition of cardiolipin caused distinct structural rearrangement including crowding of ethylene glycol groups of the tethering molecules in the inner head region and a thinning of the lipid tail region. The incorporation of NhaA in the tethered bilayers following two different protocols is quantified, and the way protein incorporation modulates the structural properties of these membranes is detailed.

A Nonionic Alcohol Soluble Polymer Cathode Interlayer Enables Efficient Organic and Perovskite Solar Cells.

The choice of interfacial materials and their properties play a critical role in determining solar cell performance and stability. For compatibility with roll-to-roll printing, it is desirable to develop stable cathode interface layers (CILs) that can be processed over the photoactive layer using orthogonal solvents. In this study, an n-type naphthalene diimide core and oligo (ethylene glycol) side-chain-based conjugated polymer is reported as a universal, efficient CIL for organic and perovskite photovoltaics. Besides good thermal stability and easy processing in alcohol/water, the new CIL is found to possess electron transport properties with an electrical conductivity of 2.3 × 10–6 S cm–1, enabling its use as a CIL with a film thickness of up to ∼35(±2) nm. Utilizing the new CIL, 16% power conversion efficiency (PCE) is achieved for organic solar cells (OSCs) based on the PM6-Y6 photoactive layer (8.9% PCE for no CIL and 15.1% with state-of-the-art CIL, PDINO), and perovskite solar cells from methylammonium lead iodide yielded a PCE of 17.6%. Compared to the reference devices, the new CIL reduced trap-assisted carrier recombination and increased the built-in potential by 80 mV, simultaneously enhancing all photovoltaic parameters. Moreover, new CIL based devices had better photostability with no burn-in losses.