Exploring the influence of hydrogen bond donor groups on the microstructure and intermolecular interactions of amorphous solid dispersions containing diflunisal structural analogues.

Drug-polymer intermolecular interactions, and H-bonds specifically, play an important role in the stabilization process of a compound in an amorphous solid dispersion (ASD). However, it is still difficult to predict whether or not interactions will form and what the strength of those interactions would be, based on the structure of drug and polymer. Therefore, in this study, structural analogues of diflunisal (DIF) were synthesized and incorporated in ASDs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) as a stabilizing polymer. The respective DIF derivatives contained different types and numbers of H-bond donor groups, which allowed to assess the influence of these structural differences on the phase behavior and the actual interactions formed in the ASDs. The highest possible drug loading of these derivatives in PVPVA were evaluated through film casting. Subsequently, a lower drug loading of each compound was spray dried. These spray dried ASDs were subjected to an in-depth solid-state nuclear magnetic resonance (ssNMR) study, including 1D spectroscopy and relaxometry, as well as 2D dipolar HETCOR experiments. The drug loading study revealed the highest possible loading of 50 wt% for the native DIF in PVPVA. The methoxy DIF derivative reached the second highest drug loading of 35 wt%, while methylation of the carboxyl group of DIF led to a sharp decrease in the maximum loading, to around 10 wt% only. Unexpectedly, the maximum loading increased again when both the COOH and OH groups of diflunisal were methylated in the dimethyl DIF derivative, to around 30 wt%. The ssNMR study on the spray dried ASD samples confirmed intermolecular H-bonding with PVPVA for native DIF and methoxy DIF. Studies of the proton relaxation decay times and 2D 1H-13C dipolar HETCOR experiments indicated that the ASDs with native DIF and methoxy DIF were homogenously mixed, while the ASDs containing DIF methyl ester and dimethyl DIF were phase separated at the nm level. It was established that, for these systems, the availability of the carboxyl group was imperative in the formation of intermolecular H-bonds with PVPVA and in the generation of homogenously mixed ASDs.

High-Temperature Hydrothermal Extraction of Phenolic Compounds from Brewer's Spent Grain and Malt Dust Biomass Using Natural Deep Eutectic Solvents.

Aligned with the EU Sustainable Development Goals 2030 (EU SDG2030), extensive research is dedicated to enhancing the sustainable use of biomass waste for the extraction of pharmaceutical and nutritional compounds, such as (poly-)phenolic compounds (PC). This study proposes an innovative one-step hydrothermal extraction (HTE) at a high temperature (120 °C), utilizing environmentally friendly acidic natural deep eutectic solvents (NADESs) to replace conventional harmful pre-treatment chemicals and organic solvents. Brewer's spent grain (BSG) and novel malt dust (MD) biomass sources, both obtained from beer production, were characterized and studied for their potential as PC sources. HTE, paired with mild acidic malic acid/choline chloride (MA) NADES, was compared against conventional (heated and stirred maceration) and modern (microwave-assisted extraction; MAE) state-of-the-art extraction methods. The quantification of key PC in BSG and MD using liquid chromatography (HPLC) indicated that the combination of elevated temperatures and acidic NADES could provide significant improvements in PC extraction yields ranging from 251% (MD-MAC-MA: 29.3 µg/g; MD-HTE-MA: 103 µg/g) to 381% (BSG-MAC-MA: 78 µg/g; BSG-HTE-MA: 375 µg/g). The superior extraction capacity of MA NADES over non-acidic NADES (glycerol/choline chloride) and a traditional organic solvent mixture (acetone/H2O) could be attributed to in situ acid-catalysed pre-treatment facilitating the release of bound PC from lignin-hemicellulose structures. Qualitative 13C-NMR and pyro-GC-MS analysis was used to verify lignin-hemicellulose breakdown during extraction and the impact of high-temperature MA NADES extraction on the lignin-hemicellulose structure. This in situ acid NADES-catalysed high-temperature pre-treatment during PC extraction offers a potential green pre-treatment for use in cascade valorisation strategies (e.g., lignin valorisation), enabling more intensive usage of available biomass waste stream resources.

Plasma Metabolite Profiling in the Search for Early-Stage Biomarkers for Lung Cancer: Some Important Breakthroughs.

Lung cancer is the leading cause of cancer-related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster, and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already been shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterized by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation to their metabolic pathways and in light of the altered cancer metabolism.

Electron-Beam-Initiated Crosslinking of Methacrylated Alginate and Diacrylated Poly(ethylene glycol) Hydrogels.

An ideal wound dressing not only needs to absorb excess exudate but should also allow for a moist wound-healing environment as well as being mechanically strong. Such a dressing can be achieved by combining both a natural (alginate) and synthetic (poly(ethylene glycol) polymer. Interestingly, using an electron beam on (meth)acrylated polymers allows their covalent crosslinking without the use of toxic photo-initiators. The goal of this work was to crosslink alginate at different methacrylation degrees (26.1 and 53.5% of the repeating units) with diacrylated poly(ethylene glycol) (PEGDA) using electron-beam irradiation at different doses to create strong, transparent hydrogels. Infrared spectroscopy showed that both polymers were homogeneously distributed within the irradiated hydrogel. Rheology showed that the addition of PEGDA into alginate with a high degree of methacrylation and a polymer concentration of 6 wt/v% improved the storage modulus up to 15,867 ± 1102 Pa. Gel fractions > 90% and swelling ratios ranging from 10 to 250 times its own weight were obtained. It was observed that the higher the storage modulus, the more limited the swelling ratio due to a more crosslinked network. Finally, all species were highly transparent, with transmittance values > 80%. This may be beneficial for the visual inspection of healing progression. Furthermore, these polymers may eventually be used as carriers of photosensitizers, which is favorable in applications such as photodynamic therapy.

Gamma radiation effects on AG MP-50 cation exchange resin and sulfonated activated carbon for bismuth-213 separation.

Medical 225Ac/213Bi radionuclide generators are designed to provide a local supply of the short-lived 213Bi for cancer treatment. However, radiation-induced damage to the sorbents commonly used in such radionuclide generators remains a major concern. In this study, the effects of gamma radiation on AG MP-50 cation exchange resin and sulfonated activated carbon (SAC) were studied by analyzing the changes in the morphological characteristics, functional groups, and the La3+/Bi3+ sorption performance, with La3+ being a suitable non-radioactive substitute for Ac3+. The surface sulfonic acid groups of AG MP-50 resin suffered from severe radiation-induced degradation, while the particle morphology was changed markedly after being exposed to absorbed doses of approximately 11 MGy. As a result, the sorption performance of irradiated AG MP-50 for La3+ and Bi3+ was significantly decreased with increasing absorbed doses. In contrast, no apparent changes in acquired morphological characteristics were observed for pristine and irradiated SAC based on SEM and XRD characterization. The surface oxygen content (e.g., O-C[double bond, length as m-dash]O) of irradiated SAC increased for an absorbed dose of 11 MGy due to free radical-induced oxidation. The sorption performance of pristine and irradiated SAC materials for La3+ and Bi3+ remained generally the same at pH values of 1 and 2. Furthermore, the applicability of AG MP-50 and SAC in the 225Ac/213Bi generators was illustrated in terms of their radiolytic stability. This study provides further evidence for the practical implementation of both AG MP-50 and SAC in 225Ac/213Bi radionuclide generators.

Partial Hydrolysis of Diphosphonate Ester During the Formation of Hybrid TiO2 Nanoparticles: Role of Acid Concentration.

The hydrolysis of the phosphonate ester linker during the synthesis of hybrid (organic-inorganic) TiO2 nanoparticles is important when forming porous hybrid organic-inorganic metal phosphonates. In the present work, a method was utilized to control the in-situ partial hydrolysis of diphosphonate ester in the presence of a titania precursor as a function of acid content, and its impact on the hybrid nanoparticles was assessed. Organodiphosphonate esters, and more specific, their hydrolysis degree during the formation of hybrid organic-inorganic metal oxide nanoparticles, are relatively under explored as linkers. Here, a detailed analysis on the hydrolysis of tetraethyl propylene diphosphonate ester (TEPD) as diphosphonate linker to produce hybrid TiO2 nanoparticles is discussed as a function of acid content. Quantitative solution NMR spectroscopy revealed that during the synthesis of TiO2 nanoparticles, an increase in acid concentration introduces a higher degree of partial hydrolysis of the TEPD linker into diverse acid/ester derivatives of TEPD. Increasing the HCl/Ti ratio from 1 to 3, resulted in an increase in degree of partial hydrolysis of the TEPD linker in solution from 4 % to 18.8 % under the applied conditions. As a result of the difference in partial hydrolysis, the linker-TiO2 bonding was altered. Upon subsequent drying of the colloidal TiO2 solution, different textures, at nanoscale and macroscopic scale, were obtained dependent on the HCl/Ti ratio and thus the degree of hydrolysis of TEPD. Understanding such linker-TiO2 nanoparticle surface dynamics is crucial for making hybrid organic-inorganic materials (i. e. (porous) metal phosphonates) employed in applications such as electronic/photonic devices, separation technology and heterogeneous catalysis.

Altering Mechanical Properties to Improve Electrode Contacts by Organic Modification of Silica-Based Ionogel Electrolytes for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) are a possible candidate to create safe, sustainable, and cost-effective batteries. Solid sodium-ion conducting organically modified ionogel electrolytes are investigated. Silica-based ionogels typically consist of an ionic liquid electrolyte (ILE) confined within a silica matrix and possess high thermal stability, good ionic conductivity, safety, and good electrochemical stability. However, they readily deteriorate when stress is applied, decreasing the electrolyte's and battery's overall performance. The mechanical characteristics of silica can be improved using organic moieties, creating Ormosils®. Silica-based ionogels with phenyl-modified silanes improve the mechanical characteristics by a reduction of their Young's modulus (from 29 to 6 MPa). This is beneficial to the charge-transfer resistance, which decreases after implementing the electrolyte in half cells, demonstrating the improved interfacial contact. Most importantly, the phenyl groups change the interacting species at the silica interface. Cationic imidazolium species pi-stacked to the phenyl groups of the silica matrix, pushing the anions to the bulk of the ILE, which affects the ionic conductivity and electrochemical stability, and might affect the quality of the SEI in half cells. In essence, the work at hand can be used as a directory to improve mechanical characteristics and modify and control functional properties of ionogel electrolytes.

Hydrogels with Reversible Crosslinks for Improved Localised Stem Cell Retention: A Review.

Successful stem cell applications could have a significant impact on the medical field, where many lives are at stake. However, the translation of stem cells to the clinic could be improved by overcoming challenges in stem cell transplantation and in vivo retention at the site of tissue damage. This review aims to showcase the most recent insights into developing hydrogels that can deliver, retain, and accommodate stem cells for tissue repair. Hydrogels can be used for tissue engineering, as their flexibility and water content makes them excellent substitutes for the native extracellular matrix. Moreover, the mechanical properties of hydrogels are highly tuneable, and recognition moieties to control cell behaviour and fate can quickly be introduced. This review covers the parameters necessary for the physicochemical design of adaptable hydrogels, the variety of (bio)materials that can be used in such hydrogels, their application in stem cell delivery and some recently developed chemistries for reversible crosslinking. Implementing physical and dynamic covalent chemistry has resulted in adaptable hydrogels that can mimic the dynamic nature of the extracellular matrix.

NMR-Metabolomics Reveals a Metabolic Shift after Surgical Resection of Non-Small Cell Lung Cancer.

BACKGROUND: Lung cancer can be detected by measuring the patient's plasma metabolomic profile using nuclear magnetic resonance (NMR) spectroscopy. This NMR-based plasma metabolomic profile is patient-specific and represents a snapshot of the patient's metabolite concentrations. The onset of non-small cell lung cancer (NSCLC) causes a change in the metabolite profile. However, the level of metabolic changes after complete NSCLC removal is currently unknown. PATIENTS AND METHODS: Fasted pre- and postoperative plasma samples of 74 patients diagnosed with resectable stage I-IIIA NSCLC were analyzed using 1H-NMR spectroscopy. NMR spectra (s = 222) representing two preoperative and one postoperative plasma metabolite profile at three months after surgical resection were obtained for all patients. In total, 228 predictors, i.e., 228 variables representing plasma metabolite concentrations, were extracted from each NMR spectrum. Two types of supervised multivariate discriminant analyses were used to train classifiers presenting a strong differentiation between the pre- and postoperative plasma metabolite profiles. The validation of these trained classification models was obtained by using an independent dataset. RESULTS: A trained multivariate discriminant classification model shows a strong differentiation between the pre- and postoperative NSCLC profiles with a specificity of 96% (95% CI [86-100]) and a sensitivity of 92% (95% CI [81-98]). Validation of this model results in an excellent predictive accuracy of 90% (95% CI [77-97]) and an AUC value of 0.97 (95% CI [0.93-1]). The validation of a second trained model using an additional preoperative control sample dataset confirms the separation of the pre- and postoperative profiles with a predictive accuracy of 93% (95% CI [82-99]) and an AUC value of 0.97 (95% CI [0.93-1]). Metabolite analysis reveals significantly increased lactate, cysteine, asparagine and decreased acetate levels in the postoperative plasma metabolite profile. CONCLUSIONS: The results of this paper demonstrate that surgical removal of NSCLC generates a detectable metabolic shift in blood plasma. The observed metabolic shift indicates that the NSCLC metabolite profile is determined by the tumor's presence rather than donor-specific features. Furthermore, the ability to detect the metabolic difference before and after surgical tumor resection strongly supports the prospect that NMR-generated metabolite profiles via blood samples advance towards early detection of NSCLC recurrence.

Solid-State Crosslinkable, Shape-Memory Polyesters Serving Tissue Engineering.

Acrylate-endcapped urethane-based precursors constituting a poly(D,L-lactide)/poly(ε-caprolactone) (PDLLA/PCL) random copolymer backbone are synthesized with linear and star-shaped architectures and various molar masses. It is shown that the glass transition and thus the actuation temperature could be tuned by varying the monomer content (0-8 wt% ε-caprolactone, Tg,crosslinked = 10-42 °C) in the polymers. The resulting polymers are analyzed for their physico-chemical properties and viscoelastic behavior (G'max = 9.6-750 kPa). The obtained polymers are subsequently crosslinked and their shape-memory properties are found to be excellent (Rr = 88-100%, Rf = 78-99.5%). Moreover, their potential toward processing via various additive manufacturing techniques (digital light processing, two-photon polymerization and direct powder extrusion) is evidenced with retention of their shape-memory effect. Additionally, all polymers are found to be biocompatible in direct contact in vitro cell assays using primary human foreskin fibroblasts (HFFs) through MTS assay (up to ≈100% metabolic activity relative to TCP) and live/dead staining (>70% viability).

Self-Induced and Progressive Photo-Oxidation of Organophosphonic Acid Grafted Titanium Dioxide.

While synthesis-properties-performance correlations are being studied for organophosphonic acid grafted TiO2 , their stability and the impact of the exposure conditions on possible changes in the interfacial surface chemistry remain unexplored. Here, the impact of different ageing conditions on the evolution of the surface properties of propyl- and 3-aminopropylphosphonic acid grafted mesoporous TiO2 over a period of 2 years is reported, using solid-state 31 P and 13 C NMR, ToF-SIMS and EPR as main techniques. In humid conditions under ambient light exposure, PA grafted TiO2 surfaces initiate and facilitate photo-induced oxidative reactions, resulting in the formation of phosphate species and degradation of the grafted organic group with a loss of carbon content ranging from 40 to 60 wt %. By revealing its mechanism, solutions were provided to prevent degradation. This work provides valuable insights for the broad community in choosing optimal exposure/storage conditions that extend the lifetime and improve the materials' performance, positively impacting sustainability.

Amino-Alkylphosphonate-Grafted TiO2: How the Alkyl Chain Length Impacts the Surface Properties and the Adsorption Efficiency for Pd.

Amino-alkylphosphonic acid-grafted TiO2 materials are of increasing interest in a variety of applications such as metal sorption, heterogeneous catalysis, CO2 capture, and enzyme immobilization. To date, systematic insights into the synthesis-properties-performance correlation are missing for such materials, albeit giving important know-how towards their applicability and limitations. In this work, the impact of the chain length and modification conditions (concentration and temperature) of amino-alkylphosphonic acid-grafted TiO2 on the surface properties and adsorption performance of palladium is studied. Via grafting with aminomethyl-, 3-aminopropyl-, and 6-aminohexylphosphonic acid, combined with the spectroscopic techniques (DRIFT, 31P NMR, XPS) and zeta potential measurements, differences in surface properties between the C1, C3, and C6 chains are revealed. The modification degree decreases with increasing chain length under the same synthesis conditions, indicative of folded grafted groups that sterically shield an increasing area of binding sites with increasing chain length. Next, all techniques confirm the different surface interactions of a C1 chain compared to a C3 or C6 chain. This is in line with palladium adsorption experiments, where only for a C1 chain, the adsorption efficiency is affected by the precursor concentration used for modification. The absence of a straightforward correlation between the number of free NH2 groups and the adsorption capacity for the different chain lengths indicates that other chain-length-specific surface interactions are controlling the adsorption performance. The increasing pH stability in the order of C1 < C3 < C6 can possibly be associated to a higher fraction of inaccessible hydrophilic sites due to the presence of folded structures. Lastly, the comparison of adsorption performance and pH stability with 3-aminopropyl(triethoxysilane)-grafted TiO2 reveals the applicability of both grafting methods depending on the envisaged pH during sorption.

Selective Pd recovery from acidic leachates by 3-mercaptopropylphosphonic acid grafted TiO2: does surface coverage correlate to performance?

Modification of metal oxides with organophosphonic acids (PAs) provides the ability to control and tailor the surface properties. The metal oxide phosphonic acid bond (M-O-P) is known to be stable under harsh conditions, making PAs a promising candidate for the recovery of metals from complex acidic leachates. The thiol functional group is an excellent regenerable scavenging group for these applications. However, the research on organophosphonic acid grafting with thiol groups is very limited. In this study, four different metal sorbent materials were designed with different thiol surface coverages. An aqueous-based grafting of 3-mercaptopropylphosphonic acid (3MPPA) on mesoporous TiO2 was employed. Surface grafted thiol groups could be obtained in the range from 0.9 to 1.9 groups per nm2. The different obtained surface properties were studied and correlated to the Pd adsorption performance. High Pd/S adsorption efficiencies were achieved, indicating the presence of readily available sorption sites. A large difference in their selectivity towards Pd removal from a spend automotive catalyst leachate was observed due to the co-adsorption of Fe on the titania support. The highest surface coverage showed the highest selectivity (K d: 530 mL g-1) and adsorption capacity (Q max: 0.32 mmol g-1) towards Pd, while strongly reducing the co-adsorption of Fe on remaining TiO2 sites.

Photocatalytic Performance of Undoped and Al-Doped ZnO Nanoparticles in the Degradation of Rhodamine B under UV-Visible Light:The Role of Defects and Morphology.

Quasi-spherical undoped ZnO and Al-doped ZnO nanoparticles with different aluminum content, ranging from 0.5 to 5 at% of Al with respect to Zn, were synthesized. These nanoparticles were evaluated as photocatalysts in the photodegradation of the Rhodamine B (RhB) dye aqueous solution under UV-visible light irradiation. The undoped ZnO nanopowder annealed at 400 °C resulted in the highest degradation efficiency of ca. 81% after 4 h under green light irradiation (525 nm), in the presence of 5 mg of catalyst. The samples were characterized using ICP-OES, PXRD, TEM, FT-IR, 27Al-MAS NMR, UV-Vis and steady-state PL. The effect of Al-doping on the phase structure, shape and particle size was also investigated. Additional information arose from the annealed nanomaterials under dynamic N2 at different temperatures (400 and 550 °C). The position of aluminum in the ZnO lattice was identified by means of 27Al-MAS NMR. FT-IR gave further information about the type of tetrahedral sites occupied by aluminum. Photoluminescence showed that the insertion of dopant increases the oxygen vacancies reducing the peroxide-like species responsible for photocatalysis. The annealing temperature helps increase the number of red-emitting centers up to 400 °C, while at 550 °C, the photocatalytic performance drops due to the aggregation tendency.

Nanobodies for the Early Detection of Ovarian Cancer.

Ovarian cancer ranks fifth in cancer-related deaths among women. Since ovarian cancer patients are often asymptomatic, most patients are diagnosed only at an advanced stage of disease. This results in a 5-year survival rate below 50%, which is in strong contrast to a survival rate as high as 94% if detected and treated at an early stage. Monitoring serum biomarkers offers new possibilities to diagnose ovarian cancer at an early stage. In this study, nanobodies targeting the ovarian cancer biomarkers human epididymis protein 4 (HE4), secretory leukocyte protease inhibitor (SLPI), and progranulin (PGRN) were evaluated regarding their expression levels in bacterial systems, epitope binning, and antigen-binding affinity by enzyme-linked immunosorbent assay and surface plasmon resonance. The selected nanobodies possess strong binding affinities for their cognate antigens (KD~0.1-10 nM) and therefore have a pronounced potential to detect ovarian cancer at an early stage. Moreover, it is of utmost importance that the limits of detection (LOD) for these biomarkers are in the pM range, implying high specificity and sensitivity, as demonstrated by values in human serum of 37 pM for HE4, 163 pM for SLPI, and 195 pM for PGRN. These nanobody candidates could thus pave the way towards multiplexed biosensors.

Changes in Metabolism as a Diagnostic Tool for Lung Cancer: Systematic Review.

Lung cancer is the leading cause of cancer-related mortality worldwide, with five-year survival rates varying from 3-62%. Screening aims at early detection, but half of the patients are diagnosed in advanced stages, limiting therapeutic possibilities. Positron emission tomography-computed tomography (PET-CT) is an essential technique in lung cancer detection and staging, with a sensitivity reaching 96%. However, since elevated 18F-fluorodeoxyglucose (18F-FDG) uptake is not cancer-specific, PET-CT often fails to discriminate between malignant and non-malignant PET-positive hypermetabolic lesions, with a specificity of only 23%. Furthermore, discrimination between lung cancer types is still impossible without invasive procedures. High mortality and morbidity, low survival rates, and difficulties in early detection, staging, and typing of lung cancer motivate the search for biomarkers to improve the diagnostic process and life expectancy. Metabolomics has emerged as a valuable technique for these pitfalls. Over 150 metabolites have been associated with lung cancer, and several are consistent in their findings of alterations in specific metabolite concentrations. However, there is still more variability than consistency due to the lack of standardized patient cohorts and measurement protocols. This review summarizes the identified metabolic biomarkers for early diagnosis, staging, and typing and reinforces the need for biomarkers to predict disease progression and survival and to support treatment follow-up.

Silanization of 3D-Printed Silica Fibers and Monoliths.

Surface functionalization of complex three-dimensional (3D) porous architectures has not been widely investigated despite their potential in different application domains. In this work, silanization was performed in silica 3D-printed porous structures, and the homogeneity of functional groups within the architecture was investigated by comparing the extent of the functionalization in the walls and core of the monolith. A silica ink was used for direct ink writing (DIW) to shape fibers and monoliths with different architectures and stacking designs. The surfaces of the fibers and monoliths were functionalized with 3-aminopropyl(triethoxysilane) (APTES) using different reaction conditions. The nature of the functional groups on the surface and the presence of RSiO1.5 bonds were identified by solid-state 13C-NMR, 29Si-NMR, and by ξ-potential measurements. Elemental analysis was used to quantify the concentration of bonded APTES in the core and walls of the monolith. The availability and hydrolytic stability of the introduced amine group on fibers were evaluated using the adsorption of PdCl42- ions within the pH range of 2-5. The study found that geometries with interfiber distances above 250 µm are homogeneously functionalized with amine groups. As the interfiber distance of the monolith decreases, a significantly lower density of amine groups is detected in the core of the monolith. The determination of the homogeneity of 3D-printed monoliths makes this work relevant as it provides the limits of functionalization carried out in stirred batch reactors for geometrically defined structures produced from a 3D-printing process.

Unraveling the Rewired Metabolism in Lung Cancer Using Quantitative NMR Metabolomics.

Lung cancer cells are well documented to rewire their metabolism and energy production networks to enable proliferation and survival in a nutrient-poor and hypoxic environment. Although metabolite profiling of blood plasma and tissue is still emerging in omics approaches, several techniques have shown potential in cancer diagnosis. In this paper, the authors describe the alterations in the metabolic phenotype of lung cancer patients. In addition, we focus on the metabolic cooperation between tumor cells and healthy tissue. Furthermore, the authors discuss how metabolomics could improve the management of lung cancer patients.

Investigating the Potential of Ethyl Cellulose and a Porosity-Increasing Agent as a Carrier System for the Formulation of Amorphous Solid Dispersions.

In the present work, an insoluble polymer, i.e., ethyl cellulose (EC), was combined with the water-soluble polyvinylpyrrolidone (PVP) as a carrier system for the formulation of amorphous solid dispersions. The rationale was that by conjoining these two different types of carriers a more gradual drug release could be created with less risk for precipitation. Our initial hypothesis was that upon contact with the dissolution medium, PVP would be released, creating a porous EC matrix through which the model drug indomethacin could diffuse. On the basis of observations of EC as a coating material, the effect of the molecular weight of PVP, and the ratio of EC/PVP on the miscibility of the polymer blend, the solid state of the solid dispersion and the drug release from these solid dispersions were investigated. X-ray powder diffraction, modulated differential scanning calorimetry, and solid-state nuclear magnetic resonance were used to unravel the miscibility and solid-state properties of these blends and solid dispersions. Solid-state nuclear magnetic resonance appeared to be a crucial technique for this aspect as modulated differential scanning calorimetry was not sufficient to grasp the complex phase behavior of these systems. Both EC/PVP K12 and EC/PVP K25 blends were miscible over the entire composition range, and addition of indomethacin did not alter this. Concerning the drug release, it was initially thought that more PVP would lead to faster drug release with a higher probability that all of the drug molecules would be able to diffuse out of the EC network as more pores would be created. However, this view on the release mechanism appeared to be too simplistic as an optimum was observed for both blends. On the basis of this work, it could be concluded that drug release from this complex ternary system was affected not only by the ratio of EC/PVP and the molecular weight of PVP but also by interactions between the three components, the wettability of the formulations, and the viscosity layer that was created around the particles.

Gaining Insight into the Role of the Solvent during Spray Drying of Amorphous Solid Dispersions by Studying Evaporation Kinetics.

Spray drying is one of the most commonly used manufacturing techniques for amorphous solid dispersions (ASDs). During spray drying, very fast solvent evaporation is enabled by the generation of small droplets and exposure of these droplets to a heated drying gas. This fast solvent evaporation leads to an increased viscosity that enables kinetic trapping of an active pharmaceutical ingredient (API) in a polymer matrix, which is favorable for the formulation of supersaturated, kinetically stabilized ASDs. In this work, the relation between the solvent evaporation rate and the kinetic stabilization of highly drug-loaded ASDs was investigated. Accordingly, thermal gravimetric analysis (TGA) was employed to study the evaporation kinetics of seven organic solvents and the influence of solutes, i.e., poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), fenofibrate (FNB), and naproxen (NAP), on the evaporation behavior. At 10 °C below the boiling point of the respective solvent, methanol (MeOH) had the lowest evaporation rate and dichloromethane (DCM) had the highest. PVPVA decreased the evaporation rate for all solvents, yet this effect was more pronounced for the relatively faster evaporating solvents. The APIs had opposite effects on the evaporation process: FNB increased the evaporation rate, while NAP decreased it. The latter might indicate the presence of interactions between NAP and the solvent or NAP and PVPVA, which was further investigated using Fourier transform-InfraRed (FT-IR) spectroscopy. Based on these findings, spray drying process parameters were adapted to alter the evaporation rate. Increasing the evaporation rate of MeOH and DCM enabled the kinetic stabilization of higher drug loadings of FNB, while the opposite trend was observed for ASDs of NAP. Even when higher drug loadings could be kinetically stabilized by adapting the process parameters, the improvement was limited, demonstrating that the phase behavior of these ASDs of FNB and NAP immediately after preparation was predominantly determined by the API-polymer-solvent combination rather than the process parameters applied.