Ultra-Microporous Fe-MOF with Prolonged NO Delivery in Biological Media for Therapeutic Application.

Nitric oxide (NO), a key element in the regulation of essential biological mechanisms, presents huge potential as therapeutic agent in the treatment and prevention of chronic diseases. Metal-organic frameworks (MOFs) with open metal sites are promising carriers for NO therapies but delivering it over an extended period in biological media remains a great challenge due to i) a fast degradation of the material in body fluids and/or ii) a rapid replacement of NO by water molecules onto the Lewis acid sites. Here, a new ultra-narrow pores Fe bisphosphonate MOF, denoted MIP-210(Fe) or Fe(H2O)(Hmbpa) (H4mbpa = p-xylenediphosphonic acid) is described that adsorbs NO due to an unprecedented sorption mechanism: coordination of NO through the Fe(III) sites is unusually preferred, replacing bound water, and creating a stable interaction with the free H2O and P-OH groups delimiting the ultra-narrow pores. This, associated with the high chemical stability of the MOF in body fluids, enables an unprecedented slow replacement of NO by water molecules in biological media, achieving an extraordinarily extended NO delivery time over at least 70 h, exceeding by far the NO kinetics release reported with others porous materials, paving the way for the development of safe and successful gas therapies.

Construction of Smart DNA-Based Drug Delivery Systems for Cancer Therapy.

Due to the disadvantages of poor targeting, slow action, and low effectiveness of current commonly used cancer treatments, including surgery, chemotherapy, and radiotherapy, researchers have turned to DNA as a biomaterial for constructing drug delivery nanocarriers. DNA is favored for its biocompatibility and programmability. In order to overcome the limitations associated with traditional drug delivery systems (DDSs), researchers have developed smart-responsive DNA DDSs that can control drug release in response to specific physical or chemical stimuli at targeted sites. In this review, a summary of multiple targeted ligand structures is provided, various shapes of stable DNA nanomaterials, and different stimuli-responsive drug release strategies in DNA DDSs. Specifically, targeted cell recognition, in vivo stable transport, and controlled drug release of smart DDSs are focused. Finally, the further development prospects and challenges of clinical application of DNA nanomaterials in the field of smart drug delivery are discussed. The objective of this review is to enhance researchers' comprehension regarding the potential application of DNA nanomaterials in precision drug delivery, with the aim of expediting the clinical implementation of intelligent DDSs.

Nonlinear differential equations and their application to evaluating the integrated impacts of multiple parameters on the biochemical safety of drinking water.

The present study aimed to narrow such gaps by applying nonlinear differential equations to biostability in drinking water. Biostability results from the integrated dynamics of nutrients and disinfectants. The linear dynamics of biostability have been well studied, while there remain knowledge gaps concerning nonlinear effects. The nonlinear effects are explained by phase plots for specific scenarios in a drinking water system, including continuous nutrient release, flush exchange with the adjacent environment, periodic pulse disinfection, and periodic biofilm development. The main conclusions are, (1) The correlations between the microbial community and nutrients go through phases of linear, nonlinear, and chaotic dynamics. Disinfection breaks the chaotic phase and returns the system to the linear phase, increasing the microbial growth potential. (2) Post-disinfection after multiple microbial peaks produced via metabolism can increase disinfection efficiency and decrease the risks associated with disinfectant byproduct risks. This can provide guidelines for optimizing the disinfection strategy, according to the long-term water safety target or a short management. Limited disinfection and ultimate disinfection may be more effective and have low chemical risk, facing longer stagnant conditions. (3) Periodic biofilm formation and biofilm detachment increase the possibility of uncertainty in the chaotic phase. For future study, nonlinear differential equation models can accordingly be applied at the molecular and ecological levels to further explore more nonlinear regulation mechanisms.

Prion strains: shining new light on old concepts.

Prion diseases are a group of inevitably fatal neurodegenerative disorders affecting numerous mammalian species, including humans. The existence of heritable phenotypes of disease in the natural host suggested that prions exist as distinct strains. Transmission of sheep scrapie to rodent models accelerated prion research, resulting in the isolation and characterization of numerous strains with distinct characteristics. These strains are grouped into categories based on the incubation period of disease in different strains of mice and also by how stable the strain properties were upon serial passage. These classical studies defined the host and agent parameters that affected strain properties, and, prior to the advent of the prion hypothesis, strain properties were hypothesized to be the result of mutations in a nucleic acid genome of a conventional pathogen. The development of the prion hypothesis challenged the paradigm of infectious agents, and, initially, the existence of strains was difficult to reconcile with a protein-only agent. In the decades since, much evidence has revealed how a protein-only infectious agent can perform complex biological functions. The prevailing hypothesis is that strain-specific conformations of PrPSc encode prion strain diversity. This hypothesis can provide a mechanism to explain the observed strain-specific differences in incubation period of disease, biochemical properties of PrPSc, tissue tropism, and subcellular patterns of pathology. This hypothesis also explains how prion strains mutate, evolve, and adapt to new species. These concepts are applicable to prion-like diseases such as Parkinson's and Alzheimer's disease, where evidence of strain diversity is beginning to emerge.

Antimicrobial activity of the recombinant peptide Melittin-Thanatin with three glycine to tryptophan mutations.

The antimicrobial peptide was considered an important target for developing novel antibacterial drugs. However, the unstable biological activity and the low antibacterial activity are challenges for the application of recombinant proteins. In this study, the fusion peptide of Melittin-Thanatin (MT) was designed and produced, and its derivative sequence (MT-W) was obtained by replacing three glycines (Gly, G) with tryptophan (Trp, W). The MT-W peptide were synthesized in Bacillus subtilis WB700 by EDDIE self-cleavage protein fusion. Compared with MT, MT-W exhibited 2-4 times higher antibacterial rate against Escherichia coli K88. In addition, MT-W showed lower cytotoxicity (IC50 > 300 mg·L-1) to the red blood cell, and more stable biological activities under the conditions of different temperatures (20, 30, 40, 50, 60, 70, 80, and 90 °C), pH values (2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, and 9.0) and different proteases. Especially, MT-W showed a broader antibacterial effect on three drug-resistant strains than florfenicol and oxytetracycline calcium. In conclusion, compared with MT, the MT-W showed increased antibacterial activity, stability, lower cytotoxicity, and broader antimicrobial effect. Therefore, it would become a promising alternative to conventional antibiotics.

Bacterial dynamics in drinking water distribution systems and flow cytometry monitoring scheme optimization.

Water biostability is desired within drinking water distribution systems (DWDSs) to limit microbiologically-related operational, aesthetic and, eventually, health-related issues. However, variations in microbiological quality can take place both spatially along DWDS pipelines and temporally at single locations due to biofilm detachment, water quality seasonality and other processes. In this study, long- and short-term trends of bacterial concentration and community structure were investigated in a secondary branch of an unchlorinated DWDS for several months using high-frequency flow cytometry (FCM) and traditional laboratory monitoring campaigns. Long-term trends of bacterial concentrations and community structures were likely caused by changes in the water physical-chemical quality (i.e. pH and conductivity). Short-term daily pattern, instead, resulted in significant variations between the bacterial concentrations and community structures at different hours, likely due to biofilm detachment and loose deposits resuspension related to changes in the local water flow. These patterns, however, showed broad variations and did not persist during the entire monitoring campaign presumably due to the stochasticity of local instantaneous demand and seasonal changes in water consumption. During periods without sensible long-term trends, the sampling hours explain a comparable or larger fraction of the bacterial community diversity compared to dates. The variations observed with FCM were poorly or not detected by traditional laboratory analyses, as the correlation between the two were rather weak, highlighting the limited information provided by traditional approaches. On the other hand, FCM data correlated with water pH and conductivity, underlining the relation between physical-chemical and microbiological water quality. Such results suggest that the advanced control of the physical-chemical water quality could minimize the microbiological water quality variations. Moreover, monitoring campaign planning should take into account the sampling time to reduce the noise caused by daily fluctuations and/or assess the overall quality variations. Finally, as monitoring costs are one of the barriers which prevent a more widespread use of FCM, a monitoring scheme optimization strategy was developed. Such strategy employs the data from an initial high-frequency sampling period to select the sampling hours which maximize the observed variations of bacterial concentration and community composition.

Electro-dewatering treatment of sludge: Assessment of the influence on relevant indicators for disposal in agriculture.

Waste activated sludge requires effective dewatering, high biological stability and retention of nutrients prior to disposal for agricultural application. The study was conducted to evaluate the impact of pressure-driven electro-dewatering (EDW) on improving sludge characteristics related to disposal in agriculture, including biological stability, pathogen availability, heavy metals concentrations and nutrients content. Thickened conditioned and mechanically dewatered sludge samples were collected from two wastewater treatment plants (WWTPs), characterized by different stabilization processes, and treated by a lab-scale device at 5, 15 and 25 V. EDW increased significantly the dry solid (DS) content, up to 43-45%, starting from 2 to 3% of raw sludge. The endogenous value of specific oxygen uptake rate (SOUR), monitored as indicator of biological stability, increased up to 56% and 39% after EDW tests for sludge from two WWTPs. On the other hand, the exogenous SOUR decreased, indicating a significant drop in the active bacterial population. Likewise, a 1-2 log unit reduction was observed for E. coli after EDW tests at 15 and 25 V. However, no remarkable removal of heavy metals, namely chromium, nickel, lead, copper and zinc, was achieved. Finally, the concentration of nutrients for soil, such as carbon, nitrogen, phosphorus and sulfur, was not affected by the EDW process. In conclusion, EDW exerts considerable effects on the biological characteristics of sludge, which should be considered in a proper design of sludge management to ensure safe and sustainable resource recovery.

In Vitro Selection of an ATP-Binding TNA Aptamer.

Recent advances in polymerase engineering have made it possible to isolate aptamers from libraries of synthetic genetic polymers (XNAs) with backbone structures that are distinct from those found in nature. However, nearly all of the XNA aptamers produced thus far have been generated against protein targets, raising significant questions about the ability of XNA aptamers to recognize small molecule targets. Here, we report the evolution of an ATP-binding aptamer composed entirely of α-L-threose nucleic acid (TNA). A chemically synthesized version of the best aptamer sequence shows high affinity to ATP and strong specificity against other naturally occurring ribonucleotide triphosphates. Unlike its DNA and RNA counterparts that are susceptible to nuclease digestion, the ATP-binding TNA aptamer exhibits high biological stability against hydrolytic enzymes that rapidly degrade DNA and RNA. Based on these findings, we suggest that TNA aptamers could find widespread use as molecular recognition elements in diagnostic and therapeutic applications that require high biological stability.

A novel method: using an adenosine triphosphate (ATP) luminescence-based assay to rapidly assess the biological stability of drinking water.

The rapid and credible evaluations of the microbial stability of a drinking water distribution system (DWDS) are of great significance for ensuring the safety of drinking water and predicting microbial pollution. Conventional biostability assessment methods mainly focus on bacterial regrowth or evaluation of the level of nutrients that support bacterial regrowth. However, such methods are time-consuming and have many limitations. An adenosine triphosphate (ATP) assay can rapidly measure all active microorganisms and is known to be a useful method to assess the microbial activity of drinking water. The measurement of ATP has been used for more than a decade in the field of drinking water research. This article reviews the application of an ATP luminescence-based method to assess the biostability of drinking water and discusses the feasibility of ATP measurement as a parameter for quickly evaluating this criterion. ATP measurement will help researchers and water managers better monitor the biological stability of drinking water from the source to the consumer's tap. This review covers the: (1) principle and application of the ATP measurement in drinking water quality assessment; (2) comparison of the merits and demerits of several methods for evaluating the biostability of drinking water; (3) discussions on using ATP measurement in evaluating biostability; and (4) improvements in the use of ATP measurement in evaluating biostability. At the end of this review, recommendations were given for better application of the ATP measurement as a parameter for monitoring the microbial quality of drinking water.

Enhancing the Stability and Immunomodulatory Activity of Liposomal Spherical Nucleic Acids through Lipid-Tail DNA Modifications.

Liposomal spherical nucleic acids (LSNAs) are an attractive therapeutic platform for gene regulation and immunomodulation due to their biocompatibility, chemically tunable structures, and ability to enter cells rapidly without the need for ancillary transfection agents. Such structures consist of small (<100 nm) liposomal cores functionalized with a dense, highly oriented nucleic acid shell, both of which are key components in facilitating their biological activity. Here, the properties of LSNAs synthesized using conventional methods, anchoring cholesterol terminated oligonucleotides into a liposomal core, are compared to LSNAs made by directly modifying the surface of a liposomal core containing azide-functionalized lipids with dibenzocyclooctyl-terminated oligonucleotides. The surface densities of the oligonucleotides are measured for both types of LSNAs, with the lipid-modified structures having approximately twice the oligonucleotide surface coverage. The stabilities and cellular uptake properties of these structures are also evaluated. The higher density, lipid-functionalized structures are markedly more stable than conventional cholesterol-based structures in the presence of other unmodified liposomes and serum proteins as evidenced by fluorescence assays. Significantly, this new form of LSNA exhibits more rapid cellular uptake and increased sequence-specific toll-like receptor activation in immune reporter cell lines, making it a promising candidate for immunotherapy.

Chemical characterization of biochar and assessment of the nutrient dynamics by means of preliminary plant growth tests.

Biochar can be produced from several organic sources with varying nutrients and metal concentrations. Four commercial grade biochars were evaluated as peat substitute. Biochars were characterised for plant nutrients and for biological stability. The results showed that there were negligible quantities of N and P and generally high levels of K and high biological stability. When these materials were mixed with peat at 10, 25 and 50% and nutrients were added to bring them to the same level of nutrients as in fertilized peat, it was found that biochar mixtures considerably reduced the levels of calcium chloride/DTPA (CAT) extractable N (including nitrate), P, and electrical conductivity- greater extent with higher rates of biochar addition except for K. The pH and K levels were increased with biochar addition. The drop in EC has important implications regarding the use of other materials used to dilute peat, for example, composted green waste, the rate of dilution is limited due to high EC and biochar addition gives the potential for higher peat dilution of these materials. Nitrate and phosphorus are very vulnerable to leaching of these nutrients in the environment in peat substrates and the binding of these by biochar has implication for leaching and nutrient application strategy. Root development using Cress test and tomato plant height and biomass using containers, were in some cases better than peat indicating that biochar could be used to dilute peat e.g. for seedling production where root development and rapid growth are very important. Application of biochars resulted in a marked reduction of N (and P) in the plant. There were significant correlation between CAT extractable N and P and corresponding plant concentration, indicating the standard growing media test, CAT, would be suitable for assessing the nutrient status of peat biochar mixes.

Amino Acid Coordination Driven Self-Assembly for Enhancing both the Biological Stability and Tumor Accumulation of Curcumin.

Clinical translation of curcumin has been highly obstructed by the rapid degradation and poor tissue absorption of this agent. Herein, we report on the generation of supramolecular curcumin nanoagents through amino acid coordination driven self-assembly to simultaneously increase the biological stability and tumor accumulation of curcumin. The biological stability of curcumin was significantly improved both through coordination and through molecular stacking. The sizes of these nanoagents can be readily manipulated to facilitate tumor accumulation. These favorable therapeutic features, together with high drug-loading capacities and responses to pH and redox stimuli, substantially enhanced the antitumor activity of curcumin without discernible side effects. Hence, supramolecular curcumin nanoagents may hold promise in moving forward the clinical application of curcumin as an effective anticancer drug.

Functional and comparative genome analysis of novel virulent actinophages belonging to Streptomyces flavovirens.

BACKGROUND: Next Generation Sequencing (NGS) technologies provide exciting possibilities for whole genome sequencing of a plethora of organisms including bacterial strains and phages, with many possible applications in research and diagnostics. No Streptomyces flavovirens phages have been sequenced to date; there is therefore a lack in available information about S. flavovirens phage genomics. We report biological and physiochemical features and use NGS to provide the complete annotated genomes for two new strains (Sf1 and Sf3) of the virulent phage Streptomyces flavovirens, isolated from Egyptian soil samples. RESULTS: The S. flavovirens phages (Sf1 and Sf3) examined in this study show higher adsorption rates (82 and 85%, respectively) than other actinophages, indicating a strong specificity to their host, and latent periods (15 and 30 min.), followed by rise periods of 45 and 30 min. As expected for actinophages, their burst sizes were 1.95 and 2.49 virions per mL. Both phages were stable and, as reported in previous experiments, showed a significant increase in their activity after sodium chloride (NaCl) and magnesium chloride (MgCl2.6H2O) treatments, whereas after zinc chloride (ZnCl2) application both phages showed a significant decrease in infection. The sequenced phage genomes are parts of a singleton cluster with sizes of 43,150 bp and 60,934 bp, respectively. Bioinformatics analyses and functional characterizations enabled the assignment of possible functions to 19 and 28 putative identified ORFs, which included phage structural proteins, lysis components and metabolic proteins. Thirty phams were identified in both phages, 10 (33.3%) of them with known function, which can be used in cluster prediction. Comparative genomic analysis revealed significant homology between the two phages, showing the highest hits among Sf1, Sf3 and the closest Streptomyces phage (VWB phages) in a specific 13Kb region. However, the phylogenetic analysis using the Major Capsid Protein (MCP) sequences highlighted that the isolated phages belong to the BG Streptomyces phage group but are clearly separated, representing a novel sub-cluster. CONCLUSION: The results of this study provide the first physiological and genomic information for S. flavovirens phages and will be useful for pharmaceutical industries based on S. flavovirens and future phage evolution studies.

Protein catalyzed capture agents with tailored performance for in vitro and in vivo applications.

We report on peptide-based ligands matured through the protein catalyzed capture (PCC) agent method to tailor molecular binders for in vitro sensing/diagnostics and in vivo pharmacokinetics parameters. A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of Bacillus anthracis discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative in situ click chemistry screens using synthetic peptide libraries. Each azide-alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti-VEGF PCC was explored as a stable in vivo imaging probe. It exhibited excellent stability against proteases and a mean elimination in vivo half-life (T1/2 ) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF in vivo. The anti-PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti-PA PCC exhibited no solution aggregation, no fragmentation when heated to 100°C, and > 81% binding activity for PA after heating at 90°C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives.

Evaluating TNA stability under simulated physiological conditions.

Chemically modified oligonucleotides are routinely used as diagnostic and therapeutic agents due to their enhanced biological stability relative to natural DNA and RNA. Here, we examine the biological stability of α-l-threofuranosyl nucleic acid (TNA), an artificial genetic polymer composed of repeating units of α-l-threofuranosyl sugars linked by 2',3'-phosphodiester bonds. We show that TNA remains undigested after 7days of incubation in the presence of either 50% human serum or human liver microsomes and is stable against snake venom phosphordiesterase (a highly active 3' exonuclease). We further show that TNA will protect internal DNA residues from nuclease digestion and shield complementary RNA strands from RNA degrading enzymes. Together, these results demonstrate that TNA is an RNA analogue with high biological stability.

The role of silica nanoparticles on long-term room-temperature stabilization of water-in-oil emulsions containing microalgae.

UNLABELLED: Prior research has demonstrated that microalgae can be stored for extended periods of time at room temperature in water-in-oil (W/O) emulsions stabilized by surface modified silica nanoparticles. However, little research has been done to examine the impact of nanoparticle concentration on emulsion stability. Such information is important for large-scale production of emulsions for microalgae storage and delivery. Studies were done to examine the impact of silica nanoparticle concentration on emulsion stability and identify the lower limit for nanoparticle concentration. Emulsion physical stability was determined using internal phase droplet size measurements and biological stability was evaluated using cell density measurements. The results demonstrate that nanoparticle concentrations as low as 0·5wt% in the oil phase can be used without significant losses in emulsion stability and microalgae viability. SIGNIFICANCE AND IMPACT OF THE STUDY: Stabilization technologies are needed for long-term storage and application of microalgae in agricultural-scale systems. While prior work has demonstrated that water-in-oil emulsions containing silica nanoparticles offer a promising solution for long-term microalgae storage at room temperature, little research has been done to examine the impact of nanoparticle concentration on emulsion stability. Here, we show the effects of silica nanoparticle concentration on maintaining physical stability of emulsions and sustaining viable cells. The results enable informed decisions to be made regarding production of emulsions containing silica nanoparticles and associated impacts on stabilization of microalgae.

Bioavailability and stability of intravenous iron sucrose originator versus generic iron sucrose AZAD.

CONTEXT: Severe iron deficiency requires intravenous iron supplementation to replenish iron stores. Intravenous iron sucrose has been used for decades for the treatment of anemia. New generic iron sucrose products are now marketed for the use in several countries and there is an ongoing discussion about the safety and efficacy of iron sucrose similars. OBJECTIVE: In this study, we compared the iron sucrose originator Venofer® and the generic iron sucrose AZAD (ISA) regarding bioavailability, toxicity and stability in human THP-1 cells and HepG2 cells. METHODS: The bioavailability of Venofer® and ISA was investigated in both cell types by a ferrozin-based assay. The release of incorporated iron was assayed by atomic absorption spectroscopy. Ferritin content was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to investigate the intracellular labile iron pool (LIP), which was measured by the fluorescent calcein assay. The amount of redox-active iron within the iron formulations was assayed using fluorescent dichlorofluorescein. RESULTS: We found no significant differences in all parameters between Venofer® and ISA in regard of bioavailability, toxicity and stability in vitro. DISCUSSION: ISA shows identical physico-chemical features and identical bioavailability in vitro. This study is a profound basis for future clinical tests with generic iron sucrose compounds.

Effect of different molecular weight organic components on the increase of microbial growth potential of secondary effluent by ozonation.

Ozonation has been widely applied in advanced wastewater treatment. In this study, the effect of ozonation on assimilable organic carbon (AOC) levels in secondary effluents was investigated, and AOC variation of different molecular weight (MW) organic components was analyzed. Although the removal efficiencies were 47%-76% and 94%-100% for UV254 and color at ozone dosage of 10mg/L, dissolved organic carbon (DOC) in secondary effluents was hardly removed by ozonation. The AOC levels increased by 70%-780% at an ozone dosage range of 1-10mg/L. AOC increased significantly in the instantaneous ozone demand phase, and the increase in AOC was correlated to the decrease in UV254 during ozonation. The results of MW distribution showed that, ozonation led to the transformation of larger molecules into smaller ones, but the increase in low MW (<1kDa) fraction did not contribute much to AOC production. The change of high MW (>100kDa and 10-100kDa) fractions itself during ozonation was the main reason for the increase of AOC levels. Furthermore, the oxidation of organic matters with high MWs (>100kDa and 10-100kDa) resulted in more AOC production than those with low MWs (1-10kDa and <1kDa). The results indicated that removing large molecules in secondary effluents could limit the increase of AOC during ozonation.

Evaluation of filler activation for sustainable FRP composite by studying properties, mechanism, and stability.

The aim is to develop new fiber-reinforced polymer (FRP) water pipe by activating fiber glass (FG) by vinyltriethoxysilane (VS) getting vinylsilane-activated FG (AFG) for filling vinylester (VE) via continuous winding to make a novel VE-AFG composite. The novelty of this work is the activation of fiber glass by vinylsilane as a single filler in vinylester and compounding them via a two-dimensional continuous winding process for the first time. The crosslinking occurred in the AFG/VE/curing agent system after activation. The activated composites increased thermal stability; 25% VE-AGF increased the degradation temperatures at 10%, 25%, and 50% weight loss by 73.3%, 10%, and 7.2%. With the activated 20% composite, values of axial strength, hoop strength, and hardness were developed by 6.3%, 2%, and 8.7%, respectively. The decay resistance to different microorganisms was increased with VE-AFG composites as a result of a sharp decrease in biodegradability percentages. The activated composites are stable toward water absorption; the least percentage was recorded by 25% VE-AFG, which minimized the water absorptivity by more than 62%. The reported characterization sentence approves enhancement of thermal, physical, and mechanical stability of sustainable vinylester-fiber glass composites manufactured by continuous winding; this is recommended for application in water pipe systems.

Prolonging the stability of cetuximab (Erbitux®) and panitumumab (Vectibix®): An orthogonal assessment of physicochemical, biological and microbiological properties of original opened glass vials and diluted saline preparations.

The two anti-epidermal growth factor receptor monoclonal antibodies (mAbs) cetuximab and panitumumab are the pillars for the treatment of EGFR-positive, KRAS wild-type metastatic colorectal cancers. However, stability data of these mAbs are generally missing or incomplete. Here, we report for the first time an orthogonal analysis of the stability of cetuximab (Erbitux®) and panitumumab (Vectibix®), either undiluted vial leftovers or saline dilutions in polyolefin/polyamide infusion bags. All samples were stored at 2-8 °C protected from light, according to their summary of product characteristics (SmPCs). Alternatively, opened vials and preparations were maintained at 25 °C for 15 h, and then stored again at 2-8 °C protected from light to mimic a temporary interruption of the cold chain. Vial leftovers proved stable up to 180 days when stored according to their SmPCs, while compounded preparations in infusion bags maintained their physiochemical, biological and microbiological stability up to 30 days. Additionally, no changes were detected up to 30 days for the same samples undergoing a thermal excursion. Our results provide additional rationale to the SmPCs, crucial especially in the case of reassignment and pre-preparation of bags. This information will allow hospitals to achieve significant cost savings, and better organization of the entire therapeutic process.