Solubility In Aqueous Solutions Research Articles

Enhancement in aqueous solubility of sulindac medicine by using the micellar solution of ionic and non-ionic surfactants

In the science of pharmacology, solubility plays a crucial role in the efficacy and bioavailability of the drug. Utilizing solubility features to improve the bioavailability and pharmacological effect of diverse weakly soluble substances, is an arduous task for pharmaceutical experts and researchers. Particle size, surface area, physicochemical qualities, physical forms of drugs, solvents and surfactant usage are parameters that influence solubility. The objective of the current study was to enhance the solubility of the non-steroidal anti-inflammatory drug (NSAID): Sulindac. The micellar solutions method was employed with different surfactants to increase the efficiency. Both nonionic (Tween 20, 40, 60 and 80 with Brij 30, 35 and 56) and ionic (SDS, SDBS, CTAB, TTAB and DTAB) surfactants were investigated for their effect on drug solubility in aqueous solution. Various parameters of surfactant solutions such as aggregation number, micelle-water partition coefficient (KM), molar solubilization ratio (MSR), Gibbs energy of solubilization (∆Gº s), size of micelle and binding constant of the drug micelles were measured. Finding reveals that the use of mentioned surfactant is an excellent approach to enhancing the solubility of sulindac. Furthermore, the present work provides an understanding of the relation of aqueous solubility with aggregation number and structure of surfactants used.

PLGA-Based Nanoplatforms in Drug Delivery for Inhibition and Destruction of Microbial Biofilm.

The biofilm community of microorganisms has been identified as the dominant mode of microbial growth in nature and a common characteristic of different microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis. The biofilm structure helps in the protection from environmental threats including host immune system and antimicrobial agents. Thus, the biofilm community has led to a higher prevalence of multidrug-resistant (MDR) strains in recent years. In this regard, the use of a new class of antibiotics, natural compounds, and anti-biofilm enzymes has been considered for the destruction of the microbial biofilm. However, different drawbacks such as low penetration, high susceptibility to degradation, instability, and poor solubility in aqueous solutions limit the use of anti-biofilm agents (ABAs) in a clinical setting. As such, recent studies have been using poly lactic-co-glycolic acid (PLGA)-based nanoplatforms (PLGA NPFs) for delivery of ABAs that have reported promising results. These particles, due to proper drug loading and release kinetics, could suppress microbial attachment, colonization, and biofilm formation for a long time. Additionally, PLGA NPFs, because of the high drug-loading efficiencies, hydrophilic surface, negative charge, and electrostatic interaction, lead to effective penetration of antibiotics to the deeper layer of the biofilm, thereby eliminating the microbial biofilm. Thus, PLGA NPFs could be considered as a potential candidate for coating catheters and other medical material surfaces for inhibition and destruction of the microbial biofilm. However, the exact interaction of PLGA NPFs and the microbial biofilm should be evaluated in animal studies. Additionally, a future goal will be to develop PLGA formulations as systems that can be used for the treatment of the MDR microbial biofilm, since the exact interactions of PLGA NPFs and these biofilm structures are not elucidated. In the present review article, we have discussed various aspects of PLGA usage for inhibition and destruction of the microbial biofilm along with different methods and procedures that have been used for improving PLGA NPF efficacy against the microbial biofilm.

Aqueous solubility of high concentrated caffeine using hydrotrope and the application to the anti-cellulite cosmetics

This study presents measurements of the aqueous solubility of caffeine at a temperature ranging from 5 to 40°C. And the low water solubility of caffeine was increased by using a hydrotropic solubilization system. Solubility was measured with a single hydrotropic system of niacinamide or betaine and a mixed hydrotropic system of niacinamide and betaine. As a result, it was possible to prepare a high-concentration aqueous caffeine solution of about 4% at 5.9°C and about 25% at 39.9°C. The modified Apelblat equation was applied to predict the temperature dependence of caffeine solubility in aqueous solutions containing niacinamide, and our experimental data showed good agreement with the correlated values. We propose the results of this study as basic data for the development of anti-cellulite cosmetics.

Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.

Asciminib is a first‐in‐class inhibitor of BCR::ABL1, specifically targeting the ABL myristoyl pocket. Asciminib is a substrate of CYP3A4 and P‐glycoprotein (P‐gp) and possesses pH‐dependent solubility in aqueous solution. This report summarizes the results of two phase I studies in healthy subjects aimed at assessing the impact of CYP3A and P‐gp inhibitors, CYP3A inducers and acid‐reducing agents (ARAs) on the pharmacokinetics (PK) of asciminib (single dose of 40 mg). Asciminib exposure (area under the curve [AUC]) unexpectedly decreased by ~40% when administered concomitantly with the strong CYP3A inhibitor itraconazole oral solution, whereas maximum plasma concentration (Cmax) decreased by ~50%. However, asciminib exposure was slightly increased in subjects receiving an itraconazole capsule (~3%) or clarithromycin (~35%), another strong CYP3A inhibitor. Macroflux studies showed that cyclodextrin (present in high quantities as excipient [40‐fold excess to itraconazole] in the oral solution formulation of itraconazole) decreased asciminib flux through a lipid membrane by ~80%. The AUC of asciminib was marginally decreased by concomitant administration with the strong CYP3A inducer rifampicin (by ~13–15%) and the strong P‐gp inhibitor quinidine (by ~13–16%). Concomitant administration of the ARA rabeprazole had little or no effect on asciminib AUC, with a 9% decrease in Cmax. The treatments were generally well tolerated. Taking into account the large therapeutic window of asciminib, the observed changes in asciminib PK following multiple doses of P‐gp, CYP3A inhibitors, CYP3A inducers, or ARAs are not considered to be clinically meaningful. Care should be exercised when administering asciminib concomitantly with cyclodextrin‐containing drug formulations.

Cografting of Zwitterionic Sulfobetaines and Cationic Amines on β-Cyclodextrin-Threaded Polyrotaxanes Facilitates Cellular Association and Tissue Accumulation with High Biocompatibility.

β-Cyclodextrins (β-CDs) and β-CD-containing polymers have attracted considerable attention as potential candidates for the treatment of cholesterol-related metabolic and intractable diseases. We have advocated the use of β-CD-threaded acid-degradable polyrotaxanes (PRXs) as intracellular delivery carriers for β-CDs. As unmodified PRXs are insoluble in aqueous solutions, chemical modification of PRXs is an essential process to improve their solubility and impart novel functionalities. In this study, we investigated the effect of the modification of zwitterionic sulfobetaines on PRXs due to their excellent solubility, biocompatibility, and bioinert properties. Sulfobetaine-modified PRXs were synthesized by converting the tertiary amino groups of precursor 2-(N,N-dimethylamino)ethyl carbamate-modified PRXs (DMAE-PRXs) using 1,3-propanesultone. The resulting sulfobetaine-modified PRXs showed high solubility in aqueous solutions and no cytotoxicity, while their intracellular uptake levels were low. To further improve this system, we designed PRXs cografted with zwitterionic sulfobetaine and cationic DMAE groups via partial betainization of the DMAE groups. Consequently, the interaction with proteins, intracellular uptake levels, and liver accumulation of partly betainized PRXs were found to be higher than those of completely betainized PRXs. Additionally, partly betainized PRXs showed no toxicity in vitro or in vivo despite the presence of residual cationic DMAE groups. Furthermore, partly betainized PRXs ameliorated the abnormal free cholesterol accumulation in Niemann-Pick type C disease patient-derived cells at lower concentrations than β-CD derivatives and previously designed PRXs. Overall, the cografting of sulfobetaines and amines on PRXs is a promising chemical modification for therapeutic applications due to the high cholesterol-reducing ability and biocompatibility of such modified PRXs. In addition, modification with both zwitterionic and cationic groups can be used for the design of various polymeric materials exhibiting both bioinert and bioactive characteristics.

Synergistic inhibition of the urinary tract pathogen Staphylococcus saprophyticus by curcumin and berberine

Staphylococcus saprophyticus is a Gram-positive pathogen that is most commonly associated with community-acquired urinary tract infections in adolescent and adult women. While antibiotics can be used to treat these infections, they often reoccur and there has been increased interest in using herbal preparations to treat them. Curcumin has been promoted as a treatment for a variety of diseases, but its effectiveness is limited by its low solubility in aqueous solutions and poor bioavailability. The sensitivity of S. saprophyticus to curcumin and berberine was determined by plate count assays, minimum inhibitory concentrations in microtiter plates, and growth kinetics. When 100 µg ml-1 berberine was combined with 20 µg ml-1 curcumin, there was a large increase in the lag phase and a decrease in the growth rate and final yield of bacteria. There was complete inhibition of growth in normal human urine. These studies indicate that a combination of curcumin with berberine allows curcumin to be used at much lower concentrations.

CO2/N2 separation by glycerol aqueous solution in a hollow fiber membrane contactor module: CFD simulation and experimental validation

In this paper, CO2 separation from CO2/N2 mixed gas was experimentally and theoretically investigated inside a gas–liquid hollow fiber membrane contactor (HFMC) module along with developing and validation of a comprehensive computational fluid dynamic (CFD) model. An aqueous solution of glycerol (10 wt%) (C3H8O3), a green and cost-effective physical solvent, was employed as the liquid absorbent, flowing in the shell side of the hollow fibers. To attain a better insight into the membrane wetting effects on separation performance, all non-wetting, partially-wetting, and completely-wetting conditions were investigated. Moreover, a correlation for CO2 Henry’s law constant was developed to estimate the CO2 solubility in aqueous solutions of glycerol via adopting the literature data. The CFD simulation results revealed that the gas to absorbent flow rate ratio (Fg/Fa) is a dominant parameter in controlling the CO2 removal efficiency. CO2 separation performance was augmented via decreasing the gas flow rate, absorption temperature and increasing the membrane porosity to tortuosity ratio as well as glycerol concentration. In contrast, by increment of the membrane wettability from non-wetting to completely-wetting condition, the CO2 removal percentage was dramatically reduced from 72.5 to 18.5%. A fair agreement between the CFD simulation results and experimental data with an absolute average relative error percentage (AARE%) of 2.7% was achieved, confirming the validity of the developed model.

A Tumor-Homing Peptide Platform Enhances Drug Solubility, Improves Blood-Brain Barrier Permeability and Targets Glioblastoma.

Simple SummaryGlioblastoma (GBM) is a fatal and incurable brain cancer, and current treatment options have demonstrated limited success. Here, we describe the use of a dg-Bcan-Targeting-Peptide (BTP-7) that has BBB-penetrating properties and targets GBM. Conjugation of BTP-7 to an insoluble anti-cancer drug, camptothecin (CPT), improves drug solubility in aqueous solution, retains drug efficacy against patient-derived GBM stem cells (GSC), enhances BBB permeability, and enables therapeutic targeting to intracranial patient-derived GBM xenograft in mice, leading to higher toxicity in GBM cells compared to normal brain tissues and prolonged animal survival. This work demonstrates a proof-of-concept for BTP-7 as a tumor-targeting peptide for therapeutic delivery to GBM. Background: Glioblastoma (GBM) is the most common and deadliest malignant primary brain tumor, contributing significant morbidity and mortality among patients. As current standard-of-care demonstrates limited success, the development of new efficacious GBM therapeutics is urgently needed. Major challenges in advancing GBM chemotherapy include poor bioavailability, lack of tumor selectivity leading to undesired side effects, poor permeability across the blood–brain barrier (BBB), and extensive intratumoral heterogeneity. Methods: We have previously identified a small, soluble peptide (BTP-7) that is able to cross the BBB and target the human GBM extracellular matrix (ECM). Here, we covalently attached BTP-7 to an insoluble anti-cancer drug, camptothecin (CPT). Results: We demonstrate that conjugation of BTP-7 to CPT improves drug solubility in aqueous solution, retains drug efficacy against patient-derived GBM stem cells (GSC), enhances BBB permeability, and enables therapeutic targeting to intracranial GBM, leading to higher toxicity in GBM cells compared to normal brain tissues, and ultimately prolongs survival in mice bearing intracranial patient-derived GBM xenograft. Conclusion: BTP-7 is a new modality that opens the door to possibilities for GBM-targeted therapeutic approaches.

Benchmark Dose Modeling Approaches for Volatile Organic Chemicals Using a Novel Air-Liquid Interface In Vitro Exposure System.

Inhalation is the most relevant route of volatile organic chemical (VOC) exposure; however, due to unique challenges posed by their chemical properties and poor solubility in aqueous solutions, in vitro chemical safety testing is predominantly performed using direct application dosing/submerged exposures. To address the difficulties in screening toxic effects of VOCs, our cell culture exposure system permits cells to be exposed to multiple concentrations at air-liquid interface (ALI) in a 24-well format. ALI exposure methods permit direct chemical-to-cell interaction with the test article at physiological conditions. In the present study, BEAS-2B and primary normal human bronchial epithelial cells (pHBEC) are used to assess gene expression, cytotoxicity, and cell viability responses to a variety of volatile chemicals including acrolein, formaldehyde, 1,3-butadiene, acetaldehyde, 1-bromopropane, carbon tetrachloride, dichloromethane, and trichloroethylene. BEAS-2B cells were exposed to all the test agents, whereas pHBECs were only exposed to the latter 4 listed above. The VOC concentrations tested elicited only slight cell viability changes in both cell types. Gene expression changes were analyzed using benchmark dose (BMD) modeling. The BMD for the most sensitive gene set was within one order of magnitude of the threshold-limit value reported by the American Conference of Governmental Industrial Hygienists, and the most sensitive gene sets impacted by exposure correlate to known adverse health effects recorded in epidemiologic and in vivo exposure studies. Overall, our study outlines a novel in vitro approach for evaluating molecular-based points-of-departure in human airway epithelial cell exposure to volatile chemicals.

In Vivo Investigation of (2-Hydroxypropyl)-β-cyclodextrin-Based Formulation of Spironolactone in Aqueous Solution for Paediatric Use.

Spironolactone (SPL), a potent anti-aldosterone steroidal drug used to treat several diseases in paediatric patients (e.g., hypertension, primary aldosteronism, Bartter’s syndrome, and congestive heart failure), is not available in child-friendly dosage forms, and spironolactone liquids have been reported to be unpalatable. Aiming to enhance SPL solubility in aqueous solution and overcome palatability, herein, the effects of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) were thoroughly investigated on solubilisation in water and on masking the unpleasant taste of SPL in vivo. Although the complexation of SPL with HP-β-CyD was demonstrated through phase solubility studies, Job’s plot, NMR and computational docking studies, our in vivo tests did not show significant effects on taste aversion. Our findings, on the one hand, suggest that the formation of an inclusion complex of SPL with HP-β-CyD itself is not necessarily a good indicator for an acceptable degree of palatability, whereas, on the other hand, they constitute the basis for investigating other cyclodextrin-based formulations of the poorly water-soluble steroidal drug, including solid dosage forms, such as spray-dried powders and orodispersible tablets.

Physicochemical Profile of Antiandrogen Drug Bicalutamide: Solubility, Distribution, Permeability.

The pharmacologically relevant physicochemical properties of the antiandrogen drug bicalutamide (BCL) have been determined for the first time. Solubility in aqueous solution, 1-octanol, n-hexane, and ethanol was measured by the shake flask method in the temperature range of 293.15–313.15 K. The compound was shown to be poorly soluble in aqueous medium and n-hexane; at the same time, an essentially higher solubility in the alcohols was revealed. The following order of molar solubility was determined: ethanol > 1-octanol > water ≈ n-hexane. The solubility was correlated with the Van’t Hoff and Apelblat equations. Evaluation of the Hansen solubility parameters and the atomic group contribution approach of Hoftyzer and Van Krevelen demonstrated consistency with the experimental data and good potential adsorption of bicalutamide. The temperature dependences of the distribution coefficients in the 1-octanol/water and n-hexane/water two-phase systems were measured and discussed in the framework of the thermodynamic approach. The ∆logD parameter determined from the distribution experiment clearly demonstrated the preference of the lipophilic delivery pathways for the compound in the biological media. The overall thermodynamic analysis based on the solubility and distribution results of the present study and the sublimation characteristics published previously has been performed. To this end, the thermodynamic parameters of the dissolution, solvation, and transfer processes were calculated and discussed in view of the solute-solvent interactions. The permeation rate of BCL through the PermeaPad barrier was measured and compared with PAMPA permeability.

Structure-Photoreactivity Relationship of 3-Hydroxyflavone-Based CO-Releasing Molecules.

Carbon monoxide (CO) is an endogenous signaling molecule that regulates diverse physiological processes. The therapeutic potential of CO is hampered by its intrinsic toxicity, and its administration poses a significant challenge. Photoactivatable CO-releasing molecules (photoCORMs) are an excellent tool to overcome the side effects of untargeted CO administration and provide precise spatial and temporal control over its release. Here, we studied the CO release mechanism of a small library of derivatives based on 3-hydroxy-2-phenyl-4H-benzo[g]chromen-4-one (flavonol), previously developed as an efficient photoCORM, by steady-state and femto/nanosecond transient absorption spectroscopies. The main objectives of the work were to explore in detail how to enhance the efficiency of CO photorelease from flavonols, bathochromically shift their absorption bands, control their acid-base properties and solubilities in aqueous solutions, and minimize primary or secondary photochemical side-reactions, such as self-photooxygenation. The best photoCORM performance was achieved by combining substituents, which simultaneously bathochromically shift the chromophore absorption spectrum, enhance the formation of the productive triplet state, and suppress the singlet oxygen production by shortening flavonol triplet-state lifetimes. In addition, the cell toxicity of selected flavonol compounds was analyzed using in vitro hepatic HepG2 cells.

Surfactant Adsorption to Gypsum Surfaces and the Effects on Solubility in Aqueous Solutions.

Vibrational sum frequency generation (VSFG) spectroscopy, conductometric titration measurements, and EDX elemental mapping were used to examine surfactant adsorption to the gypsum (010) surface and assess the effects of surfactant adsorption on gypsum solubility in aqueous solutions. Sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium chloride (DTAC) were used as anionic and cationic surfactants, respectively. Gypsum/SDS interactions result in an ordered precipitate layer on the gypsum surface after water evaporation; gypsum/DTAC interaction did not show a similar effect, despite exposure of gypsum to equivalent amounts of surfactant. VSFG spectra showed that SDS molecules adsorb with their chains parallel to the gypsum surface; spectra from gypsum surfaces treated with DTAC, however, showed no measurable response, implying that these surfactants form disorganized aggregates with no polar ordering. Vibrational data were supported by independent EDX measurements that show a uniform distribution of SDS across the gypsum surface. In contrast, element-specific EDX images showed that DTAC clustered in tightly localized patches that left most of the gypsum surface exposed. The uniform adsorption of SDS on the gypsum surface suppresses long-term dissolution up to 40% when compared to samples exposed to DTAC. Gypsum samples in DTAC-containing solutions lose approximately the same amount of material to dissolution as samples immersed in pure water.

Influence of Air Solubility on the Flotation Performance of Low-Rank Coal.

Low-rank coal (LRC) contains large amounts of harmful impurities that must be processed before utilization. Flotation is an effective means for separating fine particles, which can be influenced by air solubility in water. In this work, deaerated water (DW), ordinary water (OW), and pressurized water (PW) were prepared to research the underlying mechanism of the effect of air solubility on the flotation performance of LRC. The results show that PW dissolves the greatest amount of air in the three kinds of water (DW, OW, and PW). The flotation performance of LRC in different water types is directly proportional to air solubility in aqueous solutions. In addition, the induction time of LRC in PW (600 ms) is significantly shorter than those in OW (1200 ms) and DW (4000 ms). Atomic force microscopy (AFM) studies reveal that typical interfacial nanobubbles (NBs) only form on a highly oriented pyrolytic graphite (HOPG) surface in PW due to the supersaturated air in water. Furthermore, the interaction between LRC particles and HOPG in PW is significantly stronger than those in both OW and DW, which is attributed to the capillary force of rgw nanobubble bridge formed between particles. The hydrophobic interaction enhanced by NBs is critically important for the attachment of LRC particles to macrobubbles in flotation. Overall, air solubility in water has a great effect on LRC flotation performance, and PW flotation technology can be extended to LRC purification.

Water-Soluble Porphyrin-Based Nanoparticles Derived from Electrostatic Interaction for Enhanced Photodynamic Therapy

Pyrrole and porphyrin-derived nanoparticles have great potential use in bioimaging and therapy because of their unique magnetic, optical, and other photophysical properties, whereas the poor solubility in aqueous solution is one of the drawbacks of current photosensitizers for their photodynamic therapy (PDT) applications. Here, we developed a kind of water-soluble porphyrin-based nanoparticles that are coassembled mainly by the electrostatic interaction of anionic porphyrins and cationic tetraphenylmethane derivative. No aggregation-caused quenching (ACQ) was detected for these nanoparticles. In addition, the simple porphyrin transformation into nanoparticles improved their ability to generate reactive oxygen species singlet oxygen (1O2), which is an important factor causing apoptosis. The coassembled water-soluble porphyrin-based nanoparticles exhibited enhanced antitumor efficiency via PDT both in vitro and in vivo.

Targeted delivery of cancer drug paclitaxel to chordomas tumor cells via an RNA nanoparticle harboring an EGFR aptamer

Paclitaxel has been extensively used in clinics for cancer treatment. However, its limited solubility in aqueous solution and high occurrence of side effects have also been widely reported. In this study, we constructed a biocompatible RNA nanoparticle delivery system (3WJ-EGFRapt) that includes 3WJ (3-way junction) nanoparticle with a size of 4.85 ± 0.59 nm as a backbone and an EGFR (epidermal growth factor receptor) aptamer for specific targeting to chordomas cells, which owns the encapsulation ability of drug paclitaxel (PTX) for cancer therapy. Confocal microscopy and flow cytometry results confirmed 3WJ-EGFRapt nanoparticle exhibited excellent specific targeting to chordomas cell U-CH2 which is an EGFR(+) cell line; while the 3WJ nanoparticle lose the targeted ability. Both of the two nanoparticles own no sensitivity to lung cancer cell H520 which is an EGFR(-) cell line. Moreover, the 3WJ-EGFRapt nanoparticle encapsulated drug PTX could enhance the inhibition efficiency of chordomas tumor cells U-CH2 as compared to free PTX alone. This work demonstrates that RNA-3WJ constructed with a targeting aptamer provides a compromising targeted drug delivery ability on chordomas cells for therapeutics.

Interfacial Microextraction Boosting Nitrogen Feed for Efficient Ambient Ammonia Synthesis in Aqueous Electrolyte

AbstractThe extremely low nitrogen (N2) solubility in aqueous solution greatly limits the gas reactant supply to catalysts resulting in a bottleneck in establishing efficient electrocatalytic N2 reduction reaction (NRR). Here, aiming at fairly few N2 dissolving in aqueous electrolyte, an N2‐microextractor (NME) that can extract the N2 from water, then feed it to catalysts on electrodes, is reported. The NME consists of polymer framework and extractant that possess high solubility for N2, which serves as an ultra‐thin interfacial system wrapping around electrodes. As expected, the enhancement of N2 supply in NRR leads to a record‐high Faradaic efficiency (80.1%) with an ammonia yield rate of 58.3 µg h−1 mg−1 under ambient conditions. This is of great significance to a sustainable “Ammonia Economy.”

Extending the application potential of capillary electrophoresis/frontal analysis for drug-plasma protein studies by combining it with mass spectrometry detection.

CE/frontal analysis (CE/FA) is probably one of the most frequently used modes of CE for studying affinity interactions. It is typically performed with classic UV-Vis detection that suffers from low concentration sensitivity. To overcome this limitation, the applicability of CE/FA in combination with ESI-MS detection for the investigation of drug-HSA interactions was demonstrated. The developed new method combines the advantages of CE/FA, such as low sample consumption and no labeling or immobilization of interacting partners, with the benefits of MS detection, such as higher selectivity and sensitivity; moreover, it can be used for molecules lacking a fluorophore or chromophore. The binding parameters of tolbutamide (TL) and glimepiride (GLP), first- and second-generation antidiabetics that differ strongly in their solubility in aqueous solutions, were investigated by this CE/FA-MS method. This method, in contrast to the CE/FA method with the most commonly used UV-Vis detection, is more sensitive; an almost three times lower LOD was reached. The binding parameters of TL and GLP were investigated by this CE/FA-MS method and compared with the literature data. The binding constant value of TL obtained by UV-Vis detection was lower than the value obtained by the method hyphenated with MS detection, which is probably given by the influence of the ESI parameters on the stability of drug-HSA complex. In addition, the ratio of TL and HSA concentrations was divergent in both of the experimental approaches. Finally, it can be concluded that both detection methods have their strengths and weaknesses.

Tailoring the dissolution rate and in vitro cell response of silicon nitride coatings through combinatorial sputtering with chromium and niobium.

Ceramic coatings have been widely investigated as a means to reduce wear and metallic ion release from joint implants. Silicon nitride-based coatings have been a topic of interest specifically due to their solubility in aqueous solutions. This could imply a reduced adverse immune response since the generated debris would dissolve. However, there are concerns regarding the dissolution rate and adhesion of these silicon nitride-based coatings. This study attempts to address the concern of dissolution rate as well as coating adhesion of silicon nitride coatings. We hypothesized that alloying with chromium and niobium would affect the adhesion, dissolution rate, and the resulting ion release and cell response to the coatings. A combinatorial approach was used to deposit sputtered coatings with compositional gradients both with and without a CrN interlayer. Compositional gradients were achieved for all the investigated elements: Si (38.6-46.9 at%), Nb (2.2-4.6 at%) and Cr (1.9-6.0 at%). However, while the presence of an interlayer reduced the delamination during adhesion testing, the differences in composition in the top coating did not affect the adhesion. Nor did the top coating's composition affect the surface roughness or the coatings' inherent mechanical properties (elastic modulus and hardness). All coating compositions were associated with a low Co release from the underlying metal and points with a higher Cr content (4.3-6.0 at%) gave an overall lower release of Si, Cr and Nb ions, possibly due to the formation of a stable oxide, which reduced the dissolution rate of the coating. Optimum chromium contents were furthermore found to give an enhanced in vitro fibroblast cell viability. In conclusion, the results indicate a possibility to tailor the ion release rate, which lends promise to further investigations such as tribocorrosive tests towards a future biomedical application.

Effect of a cis-4-aminopiperidine-3-carboxylic acid (cis-APiC) residue on mixed-helical folding of unnatural peptides.

The α/β-peptide 11/9-helix and the β-peptide 12/10-helix belong to "mixed" helices, in which two types of hydrogen bonds with opposite directionality alternate along the helical axis. cis-2-Aminocyclohexanecarboxylic acid (cis-ACHC) is known to promote these mixed helices and stabilize the helical propensity more than other acyclic β-residues. Application of a mixed-helical backbone still requires sufficient solubility in aqueous solution. In this regard, we chose cis-4-aminopiperidine-3-carboxylic acid (cis-APiC) as a foldamer building block that can provide both sufficient aqueous solubility and mixed-helical propensity. Conformational analyses of α/β- and β-peptides containing a cis-APiC residue by circular dichroism spectroscopy and single-crystal X-ray crystallography suggest that the incorporation of cis-APiC instead of cis-ACHC can enhance the aqueous solubility of the mixed-helical peptides without any adverse effect on helical folding. In addition, the ratio between right- and left-handed 12/10-helices of β-peptides can be rationalized by relative energies between the local conformations of the cis-APiC residue.