Assessment of Meropenem and Vaborbactam Room Temperature and Refrigerated Stability in Polyvinyl Chloride Bags and Elastomeric Devices.

PURPOSE: Meropenem and vaborbactam is an intravenous beta-lactam/beta-lactamase inhibitor combination antibiotic active against multidrug resistant gram-negative bacteria. It may be a suitable treatment for inpatient and outpatient management of infections, and the intravenous admixture stability is therefore important for optimal utilization. The purpose of this study was to determine the stability of meropenem and vaborbactam in polyvinyl chloride (PVC) infusion bags and elastomeric pumps at room and refrigerated temperatures. METHODS: Meropenem and vaborbactam vials were reconstituted according to manufacturer instructions and diluted in PVC infusion bags to final concentrations of 4, 8, and 16 mg/mL and in elastomeric pumps to 11.4 mg/mL (n = 5 replicates per concentration and per temperature). PVC bags and elastomeric pumps were stored at room temperature (~24 °C) or in the refrigerator (~4 °C) and sampled over 12 and 144 h, respectively. Stability was defined as the duration that meropenem and vaborbactam concentrations remained ≥90% of the original concentrations. FINDINGS: All room temperature replicates across the tested concentrations retained meropenem and vaborbactam stability over 12 h and displayed concentration-dependent degradation. Refrigerated studies resulted in meropenem and vaborbactam stability at all tested concentrations up to 120 h. IMPLICATIONS: Meropenem and vaborbactam in PVC bags (4, 8, and 16 mg/mL) and elastomeric pumps (11.4 mg/mL) were stable for 12 h at room temperature and 120 h when refrigerated. These stability data allow for enhanced flexibility in the preparation, storage, wastage, and administration of meropenem and vaborbactam in the hospital and outpatient setting.

One step synthesis of boron-doped carbon nitride derived from 4-pyridylboronic acid as biosensing platforms for assessment of food safety.

The rational design of heteroatom-doped C3N4 offers a great opportunity to optimize C3N4 performance. In this communication, we propose a facile method to fabricate layered-stacked B-doped C3N4 (BCN-800) ultrathin nanosheets via a one-step calcination route. The distinctive layered-stacked structure and the presence of B atoms provide an active attachment point for antibodies and antigens. In addition, the presence of C and N might aid stability and increase conductivity. When used for vomitoxin detection, the BCN-800-based electrochemical biosensor exhibits high sensitivity with a detection limit of 0.32 pg mL-1 and superior selectivity to other interfering agents.

Analysis of Protein Glycation Using Phenylboronate Acrylamide Gel Electrophoresis.

Carbohydrate modification of proteins adds complexity and diversity to the proteome. However, undesired carbohydrate modifications also occur in the form of glycation, which have been implicated in diseases such as diabetes, Alzheimer's disease, autoimmune diseases, and cancer. The analysis of glycated proteins is challenging due to their complexity and variability. Numerous analytical techniques have been developed that require expensive specialized equipment and complex data analysis. In this chapter, we describe two easy-to-use electrophoresis-based methods that will enable researchers to detect, identify, and analyze these posttranslational modifications. This new cost-effective methodology will aid the detection of unwanted glycation products in processed foods and may lead to new diagnostics and therapeutics for age-related chronic diseases.

Monoclonal Antibodies Production Platforms: An Opportunity Study of a Non-Protein-A Chromatographic Platform Based on Process Economics.

Monoclonal antibodies currently dominate the biopharmaceutical market with growing sales having reached 80 billion USD in 2016. As most top-selling mAbs are approaching the end of their patent life, biopharmaceutical companies compete fiercely in the biosimilars market. These two factors present a strong motivation for alternative process strategies and process optimization. In this work a novel purification strategy for monoclonal antibodies comprising phenylboronic acid multimodal chromatography for capture followed by polishing by ion-exchange monolithic chromatography and packed bed hydrophobic interaction chromatography is presented and compared to the traditional protein-A-based process. Although the capital investment is similar for both processes, the operation cost is 20% lower for the novel strategy. This study shows that the new process is worthwhile investing in and could present a viable alternative to the platform process used by most industrial players.

Fabrication and response of alpha-hydroxybutyrate sensors for rapid assessment of cardiometabolic disease risk.

Early diagnosis and treatment can prevent or delay progression of early-stage type 2 diabetes and prediabetes. Unfortunately, tests such as hemoglobin A1c (HbA1c)/fasting plasma glucose (FPG) alone fail to diagnose or miscategorize up to 40% of individuals with impaired glucose tolerance (IGT) or frank diabetes based on the rarely utilized oral glucose tolerance test (OGTT). The serum metabolite alpha-hydroxybutyrate (AHB) is increasingly recognized as a reliable IGT and diabetes predictor, and can be measured using liquid chromatography-tandem mass spectrometry. However, to address AHB adoption as a population screening tool, the reliable and low-cost measurement techniques are proposed. A periodate based oxidation was performed for an AHB-based buffer, and both nitroprusside and Raman tests confirmed the formation of a slow-oxidation product. Electrochemical tests of AHB-based buffers using electrodes such as Au-honeycomb, thiol self-assembled monolayers coated Au, 2D material (black-P) coated FTO, (3-aminophenyl) triethoxysilane modified TiO2, were performed. Many of these electrodes exhibited a systematic response when AHB concentration was varied from ~1.0-12.0µg/ml. A colorimetric assay containing a vicinal-diol recognition moiety, additives, and a photoinitiator, exhibited a different color for AHB based buffer. Benesi-Hildebrand analysis indicated the association behavior of boronic acid and AHB. These methods have a potential to be used for rapid point-of-care measurements of AHB that could enhance population-wide diabetes and prediabetes screening strategies.

Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.

Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 µm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation. FROM THE CLINICAL EDITOR: The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies.

Highly Efficient Solid-Phase Labeling of Saccharides within Boronic Acid Functionalized Mesoporous Silica Nanoparticles.

Labeling is critical for the detection, quantitation, and structural identification of saccharides. However, conventional liquid-phase labeling suffers from apparent disadvantages, such as time-consuming, the presence of excessive labeling reagent, and high applicable saccharide concentration. A solid-phase approach is presented for highly efficient labeling of saccharides, using boronic acid functionalized mesoporous silica nanoparticles (MSNs) as a selective extraction sorbent and nanoscale reactor. The solid-phase labeling approach exhibited several significant advantages, including: much faster reaction speed (taking only 2 min), high product purity, and much lower applicable saccharide concentration (four orders of magnitude lower than that of liquid-phase labeling). Thus, this labeling approach opens up new avenues to the facile and efficient labeling of saccharides.

Homologation of boronic esters with organolithium compounds: a computational assessment of mechanism.

Ab initio calculations are reported for the reaction of methyl boronic ester with organolithium reagents with α-leaving groups. The best calculations rely on density functional theory prediction of structures and coupled-cluster theory calculation of accurate potential energies. The results provide strong confirmation of the feasibility of a two-step mechanism with rapid initial formation of a boron-ate complex followed by slower migration of methyl from boron to carbon with loss of the leaving group. The calculated free energy of activation is consistent with observed kinetic behavior, and the calculations provide a framework for exploring substituent and other effects on reactivity. Obtaining reasonable agreement with experiment in this way is not trivial and requires careful treatment of level of theory (density functional theory calculations tend to yield inaccurate results), of conformational complexity, especially for the ate complexes, and of the nature of the microscopic model of reactants and solvent. The methodological challenges and possible pitfalls, many of which are relevant more broadly to computational modeling of organic reaction mechanisms, are discussed in detail.

Direct synthesis of pentafluoroethyl copper from pentafluoropropionate as an economical C2F5 source: application to pentafluoroethylation of arylboronic acids and aryl bromides.

The direct synthesis of pentafluoroethyl copper (CuC2F5) from a cuprate reagent and ethyl pentafluoropropionate as one of the most economical and useful pentafluoroethyl sources was accomplished. The advantages of this method are; all the reagents employed are low-cost and operationally simple, and the CuC2F5 reagent is prepared in virtually quantitative yield. Furthermore, the CuC2F5 reagent prepared was successfully applied to two types of pentafluoroethylations with arylboronic acids and aryl bromides to provide the pentafluoroethylated aromatic products in good-to-excellent yields, including large scale operations.

A cost-effective sandwich electrochemiluminescence immunosensor for ultrasensitive detection of HIV-1 antibody using magnetic molecularly imprinted polymers as capture probes.

In this report, a rapid and cost-effective sandwich electrochemiluminescence (ECL) immunosensor was constructed for the ultrasensitive detection of human immunodeficiency virus type 1 antibody (anti-HIV-1) using magnetic molecularly imprinted polymers (MMIPs) as capture probes by combining surface and epitope imprinting techniques and antigen conjugated with horseradish peroxidase (HRP-HIV-1) as labels. First, 3-aminobenzeneboronic acid (APBA) was used as the functional monomer and cross-linking reagent, which was polymerized on the surface of silicate-coated magnetic iron oxide nanoparticles (Fe3O4@SiO2 NPs) in the presence of human immunoglobulin G (HIgG), as the template exhibiting the same Fc region but different Fab region to anti-HIV-1 after the addition of the initiator, ammonium persulfate. This process resulted in grafting a hydrophilic molecularly imprinted polymer (MIP) film on the Fe3O4@SiO2 NPs. Thus, MMIPs, which could be reused after eluting the template, were used to recognize and enrich ultra-trace levels of anti-HIV-1. Subsequently, a novel sandwich ECL immunosensor was formed through the immunoreaction between MMIPs conjugated with varied concentrations of anti-HIV-1 and HRP-HIV-1. By the catalysis of HRP immobilized onto HRP-HIV-1 on the ECL system of Luminol-H2O2, a linear response range of the anti-HIV-1 dilution ratio (standard positive serum) was achieved from 1:20,000 to 1:50, with a detection limit of 1:60,000 (S/N=3). The developed method provides a low-cost, simple, and sensitive way for the early diagnosis of HIV infected patients.