Polyethylene Glycol Molecules Research Articles

Method of hyaluronidase immobilization to produce an oral dosage form

Hyaluronidase is an enzyme that helps maintain an optimal balance of hyaluronic acid in connective tissue and ensures full tissue regeneration. Currently, hyaluronidase drugs are used in various fields of medicine. Meanwhile, there are no oral preparations based on hyaluronidase on the pharmaceutical market due to its low bioavailability in this method of administration. One of the options to increase enzyme bioavailability is electron-beam pegylation, which involves obtaining drugs with a modified pharmacokinetic profile in the direction of increasing enteral bioavailability, as well as having additional protection from the action of proteolytic enzymes. Aim of the study was using the electron beam pegylation method to obtain a laboratory batch of a preparation based on highly purified hyaluronidase, which can be further used in the development of an oral drug product. Material and methods. Hyaluronidase, which was isolated from bovine testicular hyaluronidase and polyethylene glycols of different molecular weight, was used in the experimental study. Experiments were carried out using a pulsed linear accelerator ILU-10 for enzyme electron beam immobilization on a water-soluble polymer matrix of polyethylene glycol molecules. The formation of hyaluronidase and polyethylene glycols conjugates was confirmed by exclusion chromatography. Results. As a result of accelerated electron irradiation of hyaluronidase and polyethylene glycol of molecular mass 1500 Da conjugates of enzyme and polymer matrix were formed. After electron-beam pegylation, the specific activity of the enzyme was retained. Conclusions. A laboratory batch of prototype pharmaceutical substance based on immobilised hyaluronidase on polyethylene glycol was obtained.

Polyethylene Glycol Impacts Conformation and Dynamics of Escherichia coli Prolyl-tRNA Synthetase Via Crowding and Confinement Effects.

Polyethylene glycol (PEG) is a flexible, nontoxic polymer commonly used in biological and medical research, and it is generally regarded as biologically inert. PEG molecules of variable sizes are also used as crowding agents to mimic intracellular environments. A recent study with PEG crowders revealed decreased catalytic activity of Escherichia coli prolyl-tRNA synthetase (Ec ProRS), where the smaller molecular weight PEGs had the maximum impact. The molecular mechanism of the crowding effects of PEGs is not clearly understood. PEG may impact protein conformation and dynamics, thus its function. In the present study, the effects of PEG molecules of various molecular weights and concentrations on the conformation and dynamics of Ec ProRS were investigated using a combined experimental and computational approach including intrinsic tryptophan fluorescence spectroscopy, atomic force microscopy, and atomistic molecular dynamic simulations. Results of the present study suggest that lower molecular weight PEGs in the dilute regime have modest effects on the conformational dynamics of Ec ProRS but impact the catalytic function primarily via the excluded volume effect; they form large clusters blocking the active site pocket. In contrast, the larger molecular weight PEGs in dilute to semidilute regimes have a significant impact on the protein's conformational dynamics; they wrap on the protein surface through noncovalent interactions. Thus, lower-molecular-weight PEG molecules impact protein dynamics and function via crowding effects, whereas larger PEGs induce confinement effects. These results have implications for the development of inhibitors for protein targets in a crowded cellular environment.

Nanoscintillator Coating: A Key Parameter That Strongly Impacts Internalization, Biocompatibility, and Therapeutic Efficacy in Pancreatic Cancer Models

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates

Background Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). Methods This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. Results The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC50 for the prepared PMX-GABA-AtZ conjugate was 0.048 µM, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. Conclusions The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.

Green, recyclable and high latent heat form-stable phase change composites supported by cellulose nanofibers for thermal energy management

Efficiently addressing the challenge of leakage is crucial in the advancement of solid-liquid phase change thermal storage composite materials; however, numerous existing preparation methods often entail complexity and high energy consumption. Herein, a straightforward blending approach was adopted to fabricate stable phase change nanocomposites capitalizing on the interaction between TEMPO-oxidized cellulose nanofibers (TOCNF) and polyethylene glycol (PEG) molecules. By adjusting the ratio of TOCNF to PEG and the molecular weights of PEG, TOCNF/PEG phase change composites (TPCC) with customizable phase transition temperature (40.3–59.1 °C) and high phase transition latent heat (126.3–172.1 J/g) were obtained. The TPCC of high-loaded PEG (80–95 wt%) ensured a leakage rate of less than 1.7 wt% after 100 heating-cooling cycles. Moreover, TPCC exhibits excellent optical properties with a transmittance of over 90 % at room temperature and up to 96 % after heating. The thermal response analysis of TPCC demonstrates exceptional thermal-induced flexibility and good thermal stability, as well as recyclability and reshaping ability. This study may inspire others to design bio-based phase change composites with potential applications in thermal energy storage and management of smart-energy buildings, photothermal response devices, and waste heat-generating electronics.

Effect of a nonionic surfactant and anionic polyelectrolyte binary system on the stability of a calcium and magnesium carbonates dispersion

The effect of sodium polyacrylate, polyethylene glycol of various molecular weights, and their mixtures on the dispersion stability of calcium and magnesium carbonates was studied. It was shown that in the presence of a binary system, the light transmission of the dispersion decreases 1.2–1.5 times, the content of fine fraction particles increases by 1.1–1.3 times compared to the individual components. The stability of the dispersion of carbonates depends on the components ratio in the binary system and their molecular weight. The formation of adsorption solvated layers of polyacrylate and polyethylene glycol molecules at the interphase boundary contributes to an increase in the stability of the carbonate dispersion.

Structure of polyethylene glycol/water mixtures as a separation medium of aqueous two-phase extraction systems studied by equilibrium analysis of thiocyanato complexation of Cobalt(II)

Aqueous two-phase systems (ATPS) utilizing polyethylene glycol (PEG) have been successfully used for the separation of various organic and inorganic compounds as an environmentally benign extraction method. However, a fundamental understanding of the role of the hydration structures around PEG chains in solute partitioning in ATPS remains elusive although it has been considered that PEG molecules are involved in separation. In the present work, the equilibria of Co(II) thiocyanate complexation reaction in aqueous PEG solutions were studied by spectrophotometry with varying ethylene oxide chain length and concentration of PEG. From the formation constants of the tetrahedral and octahedral Co(II) thiocyanate complexes obtained, a microheterogeneous structure consisting of pseudo phases formed by hydration of ethylene oxide (EO) chain and terminal hydroxyl (OH) groups in the PEG molecule in addition to the bulk water phase was estimated. It was revealed that the formation of tetrahedral Co(NCS)42− complex proceeds in the EO pseudo phase by the involvement of hydrophobic ethylene groups, while the OH phase and the bulk phase inhibit the progress of the reaction. This indicates that Co(NCS)42− is stable in hydrophobic hydration structure of water around the EO moiety. The EO phase imparts hydrophobicity to aqueous PEG solutions and plays a predominant role in partition of solute molecules in PEG-based ATPS.

Color adjustable, mechanically robust, flame-retardant and weather-resistant TiO2/MMT/CNF hierarchical nanocomposite coatings toward intelligent fire cyclic warning and protection

Fire safety and protection are very important but still show a critical global challenge. Developing smart fire warning materials with combined passive flame retardancy and active fire alarm response is promising for reducing or avoiding serious fire disasters. Various nano-fillers (e.g., graphene oxide and MXene) based composite coatings have proven to be effective for monitoring critical fire risk of various combustible materials; however, they still show some shortages, for example, high cost, black color, poor weather resistance and complicated fabricating process. Here, we report a green, cost-effective and large-scale strategy for fabricating water-based 3D-titania/2D-montmorillonite/1D-celluose nanofiber (TiO2/MMT/CNF) hierarchical nanocomposite coatings with adjustable color, mechanical robustness, good flame retardancy, long-term weather resistance and sensitive fire cyclic alarming response. The formation of strong chemical bonding and hydrogen bonding interactions among polyethylene glycol molecules and multi-scale nano-fillers together with silane surface modification can produce good mechanical flexibility (folded crane), surface hydrophobicity (water contact angle of 152°) and exceptional flame resistance (good structure integrity after 120 s flame exposure). Notably, the optimized nanocomposite coatings exhibit ultrafast fire alarm response (<3.5 s) and stable fire cyclic alarming capability via the possible band transition of the TiO2 network under flame. Further, such color-adjustable nanocomposite coatings can be easily fabricated for large-scale production, and they show excellent stable flame retardancy and stable fire cyclic warning response even after more than one-year outdoor exposure. This work provides a promising and green fire-warning nanocomposite coatings with combined passive-active functionalities for fire warning and protection.

Surface Modification of Titanate Nanotubes with a Carboxylic Arm for Further Functionalization Intended to Pharmaceutical Applications.

Nanotechnology is playing a significant role in modern life with tremendous potential and promising results in almost every domain, especially the pharmaceutical one. The impressive performance of nanomaterials is shaping the future of science and revolutionizing the traditional concepts of industry and research. Titanate nanotubes (TNTs) are one of these novel entities that became an appropriate choice to apply in several platforms due to their remarkable properties such as preparation simplicity, high stability, good biocompatibility, affordability and low toxicity. Surface modification of these nanotubes is also promoting their superior characters and contributing more to the enhancement of their performance. In this research work, an attempt was made to functionalize the surface of titanate nanotubes with carboxylic groups to increase their surface reactivity and widen the possibility of bonding different molecules that could not be bonded directly. Three carboxylic acids were investigated (trichloroacetic acid, citric acid and acrylic acid), and the prepared composites were examined using FT-IR and Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The toxicity of these functionalized TNTs was also investigated using adherent cancer cell lines and fibroblasts to determine their safety profile and to draw the basic lines for their intended future application. Based on the experimental results, acrylic acid could be the suitable choice for permanent surface modification with multiple carboxylic groups due to its possibility to be polymerized, thus presenting the opportunity to link additional molecules of interest such as polyethylene glycol (PEG) and/or other molecules at the same time.

In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole.

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.

Impact of polyethylene glycol molar mass and structural isomer of alcohol on the solubility and dissolution enhancement of mesalazine

This work reports the solubility of mesalazine (5-ASA) in mole fraction terms (x1,T) in mono-solvents of polyethylene glycol (PEG) 400, 1-propanol and 2-propanol along with their binary mixtures in different mass fractions of PEG 400 at 293.15–313.15 K and atmospheric pressure which measured experimentally by a shake-flask technique. The solubility of 5-ASA in these mixtures not only enhances with enhancing temperature, but also raises with raising PEG's mass fraction. Effect of PEG molar mass on the solubility of 5-ASA was also estimated by measuring its solubility in PEG 200 or 600 + 1- or 2-propanol mixtures at 298.15 K. Upon the same temperature and mass fraction of PEGs, the upward trend of 5-ASA mole fractions was: PEG 600 + 1-propanol > PEG 600 + 2-propanol > PEG 400 + 1-propanol > PEG 400 + 2-propanol > PEG 200 + 1-propanol > PEG 200 + 2-propanol indicating, the binary mixtures containing a high molar mass of PEG and 1-propanol with a hydroxyl group attached to carbon number 1 had a more solubilization power. Then, the experimental mole fractions were modelled by some cosolvency and activity coefficient models, and the model parameters were regressed. The back-computed mole fractions of 5-ASA by cosolvency models presented a better agreement with the experimental data than that of activity models and Jouyban-Acree model had the best performance (low overall average percentage deviation of 6.1 %). By means of enthalpy-entropy compensation analysis, non-linear ΔsolH° against ΔsolG° compensation plots with positive and negative slopes were achieved as a consequent of increasing 5-ASA solvation by PEG molecules and the solvent-structure loosing, respectively.

Macromolecular crowding potently stimulates DNA supercoiling activity of Mycobacterium tuberculosis DNA gyrase

Macromolecular crowding, manifested by high concentrations of proteins and nucleic acids in living cells, significantly influences biological processes such as enzymatic reactions. Studying these reactions in vitro, using agents such as polyethylene glycols (PEGs) and polyvinyl alcohols (PVAs) to mimic intracellular crowding conditions, is essential due to the notable differences from enzyme behaviors observed in diluted aqueous solutions. In this article, we studied Mycobacterium tuberculosis (Mtb) DNA gyrase under macromolecular crowding conditions by incorporating PEGs and PVAs into the DNA supercoiling reactions. We discovered that high concentrations of potassium glutamate, glycine betaine, PEGs, and PVA substantially stimulated the DNA supercoiling activity of Mtb DNA gyrase. Steady-state kinetic studies showed that glycine betaine and PEG400 significantly reduced the KM of Mtb DNA gyrase, and simultaneously increased the Vmax or kcat of Mtb DNA gyrase for ATP and the plasmid DNA molecule. Molecular dynamics simulation studies demonstrated that PEG molecules kept the ATP lid of GyrB in a closed or semi-closed conformation, which prevented ATP molecules from leaving the ATP-binding pocket of GyrB. The stimulation of the DNA supercoiling activity of Mtb DNA gyrase by these molecular crowding agents likely results from a decrease in water activity and an increase in excluded volume.

A Simple and Versatile Strategy for Oriented Immobilization of His-Tagged Proteins on Magnetic Nanoparticles.

Oriented and covalent immobilization of proteins on magnetic nanoparticles (MNPs) is particularly challenging as it requires both the functionality of the protein and the colloidal stability of the MNPs to be preserved. Here, we describe a simple, straightforward, and efficient strategy for MNP functionalization with proteins using metal affinity binding. Our method involves a single-step process where MNPs are functionalized using a preformed, ready-to-use nitrilotriacetic acid-divalent metal cation (NTA-M2+) complex and polyethylene glycol (PEG) molecules. As a proof-of-concept, we demonstrate the oriented immobilization of a recombinant cadherin fragment engineered with a hexahistidine tag (6His-tag) onto the MNPs. Our developed methodology is simple and direct, enabling the oriented bioconjugation of His-tagged cadherins to MNPs while preserving protein functionality and the colloidal stability of the MNPs, and could be extended to other proteins expressing a polyhistidine tag. When compared to the traditional method where NTA is first conjugated to the MNPs and afterward free metal ions are added to form the complex, this novel strategy results in a higher functionalization efficiency while avoiding MNP aggregation. Additionally, our method allows for covalent bonding of the cadherin fragments to the MNP surface while preserving functionality, making it highly versatile. Finally, our strategy not only ensures the correct orientation of the protein fragments on the MNPs but also allows for the precise control of their density. This feature enables the selective targeting of E-cadherin-expressing cells only when MNPs are decorated with a high density of cadherin fragments.

Site-Specific Modification of Single Domain Antibodies by Enzyme-Immobilized Magnetic Beads.

Nanobodies as imaging agents and drug conjugates have shown great potential for cancer diagnostics and therapeutics. However, site-specific modification of a nanobody with microbial transglutaminase (mTGase) encounters problems in protein separation and purification. Here, we describe a facile yet reliable strategy of immobilizing mTGase onto magnetic beads for site-specific nanobody modification. The mTGase immobilized on magnetic beads (MB-mTGase) exhibits catalytic activity nearly equivalent to that of the free mTGase, with good reusability and universality. Magnetic separation simplifies the protein purification step and reduces the loss of nanobody bioconjugates more effectively than size exclusion chromatography. Using MB-mTGase, we demonstrate site-specific conjugation of nanobodies with fluorescent dyes and polyethylene glycol molecules, enabling targeted immunofluorescence imaging and improved circulation dynamics and tumor accumulation in vivo. The combined advantages of MB-mTGase method, including high conjugation efficiency, quick purification, less protein loss, and recycling use, are promising for site-specific nanobody functionalization and biomedical applications.

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates

Background: Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). Methods: This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. Results: The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC50 for the prepared PMX-GABA-AtZ conjugate was 0.048 µM, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. Conclusions: The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.

PEGylated therapeutics in the clinic.

The covalent attachment of polyethylene glycol (PEG) to therapeutic agents, termed PEGylation, is a well-established and clinically proven drug delivery approach to improve the pharmacokinetics and pharmacodynamics of drugs. Specifically, PEGylation can improve the parent drug's solubility, extend its circulation time, and reduce its immunogenicity, with minimal undesirable properties. PEGylation technology has been applied to various therapeutic modalities including small molecules, aptamers, peptides, and proteins, leading to over 30 PEGylated drugs currently used in the clinic and many investigational PEGylated agents under clinical trials. Here, we summarize the diverse types of PEGylation strategies, the key advantages of PEGylated therapeutics over their parent drugs, and the broad applications and impacts of PEGylation in clinical settings. A particular focus has been given to the size, topology, and functionalities of PEG molecules utilized in clinically used PEGylated drugs, as well as those under clinical trials. An additional section has been dedicated to analyzing some representative PEGylated drugs that were discontinued at different stages of clinical studies. Finally, we critically discuss the current challenges faced in the development and clinical translation of PEGylated agents.

Anti-HER2 Super Stealth Immunoliposomes for Targeted-Chemotherapy.

Liposomes play an important role in the field of drug delivery by virtue of their biocompatibility and versatility as carriers. Stealth liposomes, obtained by surface decoration with hydrophilic polyethylene glycol (PEG) molecules, represent an important turning point in liposome technology, leading to significant improvements in the pharmacokinetic profile compared to naked liposomes. Nevertheless, the generation of effective targeted liposomes-a central issue for cancer therapy-has faced several difficulties and clinical phase failures. Active targeting remains a challenge for liposomes. In this direction, a new Super Stealth Immunoliposomes (SSIL2) composed of a PEG-bi-phospholipids derivative is designed that stabilizes the polymer shielding over the liposomes. Furthermore, its counterpart, conjugated to the fragment antigen-binding of trastuzumab (Fab'TRZ -PEG-bi-phospholipids), is firmly anchored on the liposomes surface and correctly orients outward the targeting moiety. Throughout this study, the performances of SSIL2 are evaluated and compared to classic stealth liposomes and stealth immunoliposomes in vitro in a panel of cell lines and in vivo studies in zebrafish larvae and rodent models. Overall, SSIL2 shows superior in vitro and in vivo outcomes, both in terms of safety and anticancer efficacy, thus representing a step forward in targeted cancer therapy, and valuable for future development.

Photo-thermal conversion properties of Cr, Mo, and W nanofluids in polyethylene glycol prepared by laser ablation in liquid method for direct absorption solar collectors applications

Nanofluids (NFs) are promising materials for solar-energy harvesting. The main drawback of NFs is their instability and longtime preparation methods that the purpose of this work relies on overcoming these problems. The Cr, Mo, and W NFs in polyethylene glycol (PEG) were synthesized by laser ablation in liquid (LAL). The capability of the prepared NFs in photo-thermal conversion was investigated under 60 min solar simulator irradiation at 1 Sun and thermo-physical properties of them (SER, Etotal, E%, and B) were calculated, indicating Cr NF has the highest photo-thermal conversion efficiency (E%≅85% at its near-to-surface). The comparison of nanoparticles radius obtained with transmission electron microscopy (TEM) and the hydrodynamic radius obtained with dynamic light scattering (DLS) methods, reveals that nanoparticles were surrounded by a thick layer of PEG molecules, leading to the super-stable and long-life NFs. The effect of the nanoparticle concentration, light intensity, and consecutive heating–cooling cycles on the performance of NFs was investigated. Under 1 h sunlight illumination (∼850–960 W/m2 intensity), the surface temperature of Cr NF reaches ≅ 65 ℃, indicating the Cr NF is highly eligible for photo-thermal conversion in the real outdoor condition. The low cost and simplicity of the synthesis method, no need to use stabilizer, super durability, high-thermal stability, low rate constant of heat dissipation, and high photo-thermal conversion efficiency confirms that Cr/PEG NF can be used as potential working fluid for direct absorption solar collectors (DASCs).

Matrix Effects of Urine Marker Substances in LC-MS/MS Analysis of Drug of Abuse.

Analysis of drug abuse is frequently performed using high-performance liquid chromatography with an MS/MS detector and electrospray ionization. In this context, matrix effects, like signal reduction by ion suppression of individual analytes, play an important role. In this study, the authors evaluated the matrix effect caused by polyethylene glycol (PEG) with chain lengths ranging from 6 to 12 repeating units in drug analysis by LC-MS/MS. Selected chain lengths were used in the Ruma urine marker system. Amphetamines, opiates, opioids, antidepressants, psychotics, benzodiazepines, z-substances, and individual drugs, including THCCOOH, cocaine, LSD, and some of their metabolites were investigated. The matrix effect was investigated at PEG concentrations of 500 mcg/mL and 20 mcg/mL. The effect of each PEG molecule was determined. Furthermore, the effects of different common sample preparations on the PEG matrix effects were evaluated. There was a strong correlation between the retention time of PEG and the drug that was ion-suppressed by PEG. The matrix effect decreased to the point where it was within an acceptable range at the lower PEG concentrations investigated in this study. Matrix effects were observed for drugs with approximately the same retention times as the individual PEGs. The influence of the different workup methods was not as clear, which may be because of the similar solubilities of the PEGs and some analytes. At low PEG concentrations, the matrix effect was always below 60%, except for nortilidine. All the drugs were detectable. The effect on quantification was less than 15% for substances with deuterated analytes as internal standards and less than 32% for analytes without their own internal standards.

Placental drug transport and fetal exposure during pregnancy is determined by drug molecular size, chemistry, and conformation

Pregnant people are unable to take many prescription and over-the-counter medications because of suspected or known risk to the fetus. This undermedication contributes to the high maternal mortality rate in the United States and detracts from the quality of life of pregnant people. As such, there is an urgent need to develop safe pharmaceutical formulations for use during pregnancy. Most drugs are small molecules that easily cross the placenta, which is the biological barrier that separates the maternal and fetal bloodstreams. One potential approach to preventing fetal drug accumulation is to design drug compounds that are excluded by the placenta; however, there is little understanding of how macromolecular drug properties affect transplacental transport. To address this knowledge gap, we examined the transport behavior of fluorescently-labeled polymers with varying size, conformation, and chemistry. We compared these polymers to unconjugated fluorescein, a small molecule model drug that readily crosses biological barriers. We found that molecular size affected transplacental transport in an in vitro model, BeWo b30 monolayers, as well as in pregnant mice, with larger polymers having lower permeability. In addition to size, polymer chemistry altered behavior, with polyethylene glycol (PEG) molecules permeating the placental barrier to a greater extent than dextrans of equivalent molecular weight. PEG molecules were also more readily taken up into placental cells in vivo. These findings will inform the future development of drug conjugates or other macromolecular medicines that can safely be used during pregnancy.