Solvation of Model Biomolecules in Choline-Aminoate Ionic Liquids: A Computational Simulation Using Polarizable Force Fields.

One can foresee a very near future where ionic liquids will be used in applications such as biomolecular chemistry or medicine. The molecular details of their interaction with biological matter, however, are difficult to investigate due to the vast number of combinations of both the biological systems and the variety of possible liquids. Here, we provide a computational study aimed at understanding the interaction of a special class of biocompatible ionic liquids (choline-aminoate) with two model biological systems: an oligopeptide and an oligonucleotide. We employed molecular dynamics with a polarizable force field. Our results are in line with previous experimental and computational evidence on analogous systems and show how these biocompatible ionic liquids, in their pure form, act as gentle solvents for protein structures while simultaneously destabilizing DNA structure.

Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance.

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.

Attosecond-Level Delay Sensing via Temporal Quantum Erasing.

Traditional Hong-Ou-Mandel (HOM) interferometry, insensitive to photons phase mismatch, proved to be a rugged single-photon interferometric technique. By introducing a post-beam splitter polarization-dependent delay, it is possible to recover phase-sensitive fringes, obtaining a temporal quantum eraser that maintains the ruggedness of the original HOM with enhanced sensitivity. This setup shows promising applications in biological sensing and optical metrology, where high sensitivity requirements are coupled with the necessity to keep light intensity as low as possible to avoid power-induced degradation. In this paper, we developed a highly sensitive single photon birefringence-induced delay sensor operating in the telecom range (1550 nm). By using a temporal quantum eraser based on common path Hongr-Ou-Mandel Interferometry, we were able to achieve a sensitivity of 4 as for an integration time of 2·104 s.

Assessment of vibrational-translational relaxation dynamics of in a wet-nitrogen matrix through QEPAS.

Here we report on a study of the non-radiative relaxation dynamic of 12CH4 and 13CH4 in wet nitrogen-based matrixes by using the quartz-enhanced photoacoustic spectroscopy (QEPAS) technique. The dependence of the QEPAS signal on pressure at fixed matrix composition and on H2O concentration at fixed pressure was investigated. We demonstrated that QEPAS measurements can be used to retrieve both the effective relaxation rate in the matrix, and the V-T relaxation rate associated to collisions with nitrogen and water vapor. No significant differences in measured relaxation rates were observed between the two isotopologues.

Electrical and Mechanical Characterisation of Poly(ethylene)oxide-Polysulfone Blend for Composite Structural Lithium Batteries.

In this work, a blend of PEO, polysulfone (PSF), and lithium bis(trifluoromethanesulfonyl)imide (LiTFSi) was prepared at different PEO-PSf weight ratios (70-30, 80-20, and 90-10) and ethylene oxide to lithium (EO/Li) ratios (16/1, 20/1, 30/1, and 50/1). The samples were characterised using FT-IR, DSC, and XRD. Young's modulus and tensile strength were evaluated at room temperature with micro-tensile testing. The ionic conductivity was measured between 5 °C and 45 °C through electrochemical impedance spectroscopy (EIS). The samples with a ratio of PEO and PSf equal to 70-30 and EO/Li ratio equal to 16/1 have the highest conductivity (1.91 × 10-4 S/cm) at 25 °C, while the PEO-PSf 80-20 EO/Li = 50/1 have the highest averaged Young's modulus of about 1.5 GPa at 25 °C. The configuration with a good balance between electrical and mechanical properties is the PEO-PSf 70-30 EO/Li = 30/1, which has a conductivity of 1.17 × 10-4 S/cm and a Young's modulus of 800 MPa, both measured at 25 °C. It was also found that increasing the EO/Li ratio to 16/1 dramatically affects the mechanical properties of the samples with them showing extreme embrittlement.

Development of Solid Lipid Nanoparticles as Dry Powder: Characterization and Formulation Considerations.

Solid lipid nanoparticles (SLNs) are lipid-based colloidal systems used for the delivery of active compounds. Although SLNs have many benefits, they show important issues due to physical and chemical instability phenomena during storage. For these reasons, it is highly desirable to have a dried SLN formulation available. Therefore, the aim of the project was to identify suitable methods to obtain a dry powder formulation from an SLN suspension. The nanoparticle suspension was dried using both freeze- and spray-drying techniques. The suitability of these methods in obtaining SLN dry powders was evaluated from the analyses of nanotechnological parameters, system morphology and thermal behavior using differential scanning calorimetry. Results pointed out that both drying techniques, although at different yields, were able to produce an SLN dry powder suitable for pharmaceutical applications. Noteworthily, the freeze-drying of SLNs under optimized conditions led to a dry powder endowed with good reconstitution properties and technological parameters similar to the starting conditions. Moreover, freeze-thaw cycles were carried out as a pretest to study the protective effect of different cryoprotectants (e.g., glucose and mannitol with a concentration ranging from 1% to 10% w/v). Glucose proved to be the most effective in preventing particle growth during freezing, thawing, and freeze-drying processes; in particular, the optimum concentration of glucose was 1% w/v.

Ethyl Protocatechuate Encapsulation in Solid Lipid Nanoparticles: Assessment of Pharmacotechnical Parameters and Preliminary In Vitro Evaluation for Colorectal Cancer Treatment.

Colorectal cancer is one of the most diffused tumoral diseases. Since most medicaments employed for its treatment are debilitating, the use of naturally derived products, which can be effective against the mutated cells and, in addition, can reduce most inflammatory-related effects, could be extremely beneficial for the continued treatment of this disease. In this research, ethyl protocatechuate (PCAEE), a protocatechuic acid prodrug, was encapsulated in solid lipid nanoparticles (SLN) (prepared without and with Tween 80), which were characterized in terms of size, polydispersity index (PDI), zeta potential and thermotropic behavior. Encapsulation efficiency, release profile and interaction with a model of biomembrane were also assessed. The nanoparticles were tested in vitro on both healthy cells and on a model of tumoral cells. SLN prepared with Tween 80 was promising in terms of physicochemical properties (z-average of 190 nm, PDI 0.150 and zeta potential around -20 mV) and encapsulation efficiency (56%); they showed a desirable release profile, demonstrated an ability to penetrate and release the encapsulated PCAEE into a biomembrane model and were nontoxic on healthy cells. In addition, they caused a greater dose-dependent decrease in the viability of CaCo-2 cells than PCAEE alone. In conclusion, the formulation could be proposed for further studies to assess its suitability for the treatment of colorectal cancer.

A Thermodynamic Study on the Interaction between RH-23 Peptide and DMPC-Based Biomembrane Models.

Investigation of the interaction between drugs and biomembrane models, as a strategy to study and eventually improve drug/substrate interactions, is a crucial factor in preliminary screening. Synthesized peptides represent a source of potential anticancer and theragnostic drugs. In this study, we investigated the interaction of a novel synthesized peptide, called RH-23, with a simplified dimyristoylphosphatidylcholine (DMPC) model of the cellular membrane. The interaction of RH-23 with DMPC, organized either in multilamellar vesicles (MLVs) and in Langmuir-Blodgett (LB) monolayers, was assessed using thermodynamic techniques, namely differential scanning calorimetry (DSC) and LB. The calorimetric evaluations showed that RH-23 inserted into MLVs, causing a stabilization of the phospholipid gel phase that increased with the molar fraction of RH-23. Interplay with LB monolayers revealed that RH-23 interacted with DMPC molecules. This work represents the first experimental thermodynamic study on the interaction between RH-23 and a simplified model of the lipid membrane, thus providing a basis for further evaluations of the effect of RH-23 on biological membranes and its therapeutic/diagnostic potential.

Interaction of Lipophilic Cytarabine Derivatives with Biomembrane Model at the Air/Water Interface.

Cell membrane models are useful for obtaining molecular-level information on the interaction of biologically active molecules whose activity is believed to depend also on their effects on the membrane. Cytarabine was conjugated with fatty acids to improve the drug lipophilicity and the interaction with the biomembrane model. Cytarabine was conjugated with fatty acids of different lengths to form the trimyristoyl cytarabine and the tristearoyl cytarabine derivatives. Their interaction with biomembrane models constituted by dimyristoylphosphatidylcholine (DMPC) monolayers was studied by employing the Langmuir-Blodgett technique. DMPC/cytarabine, DMPC/trimyristoyl cytarabine and DMPC/tristearoyl cytarabine mixed monolayers at increasing molar fractions of the compound were prepared and placed on the subphase. The mean molecular area/surface pressure isotherms were recorded at 37 °C. Between the molecules of DMPC and those of cytarabine or prodrugs, repulsive forces act. However, these forces are very weak between DMPC and cytarabine and stronger between DMPC and the cytarabine derivatives, thus avoiding the expulsion of the compounds at higher surface pressure and modifying the stability of the mixed monolayer. The fatty acid moieties could then modulate the affinity of cytarabine for biomembranes.

Benzo[k,l]xanthene Lignan-Loaded Solid Lipid Nanoparticles for Topical Application: A Preliminary Study.

Skin is the first human barrier that is daily exposed to a broad spectrum of physical and chemical agents, which can increase reactive oxygen species (ROS) and lead to the formation of topical disorders. Antioxidant molecules, such as benzo[k,l]xanthene lignans (BXL), are ideal candidates to eliminate or minimize the effects of ROS. Herein, we aimed to formulate BXL-loaded solid lipid nanoparticles (SLN-BXL) to improve the bioavailability and interaction with the skin, and also to investigate the protective impact against intracellular ROS generation in HFF-1 in comparison with the drug-free situation. SLN-BXL were formulated using the PIT/ultrasonication method, and then were subjected to physicochemical characterizations, i.e., average size, zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency (%EE), thermotropic behavior, and interaction with a biomembrane model. The results show a mean size around 200 nm, PDI of 0.2, and zeta potential of about -28 mV, with values almost unchanged over a period of three months, while the EE% is ≈70%. Moreover, SLN-BXL are able to deeply interact with the biomembrane model, and to achieve a double-action release in mildly hydrophobic matrices; the results of the in vitro experiments confirm that SLN-BXL are cell-safe and capable of attenuating the IL-2-induced high ROS levels. In conclusion, based on our findings, the formulation can be proposed as a candidate for a preventive remedy against skin disorders induced by increased levels of ROS.

The role of hypochlorous acid in the management of eye infections: a case series.

Experiences from clinical practice suggest that hypochlorous acid (HOCl) used as adjuvant treatment can shorten the time to clinical resolution of blepharitis, particularly in relation to the ophthalmic complications that often occur with a blepharitis diagnosis. In addition, in clinical practice, HOCl adjuvant treatment also resulted in a viable option for the management of ophthalmic disorders other than blepharitis. This case series presents and discusses real-life experiences with using an HOCl ophthalmic spray to manage eye infections, further characterizing the use of HOCl for ophthalmic applications.

Great Abilities of Shinella zoogloeoides Strain from a Landfarming Soil for Crude Oil Degradation and a Synergy Model for Alginate-Bead-Entrapped Consortium Efficiency.

Oil contamination is of great concern worldwide and needs to be properly addressed. The present work aimed to contribute to the development of bacterial consortia for oil recovery. We investigated the community structure of a landfarming-treated soil (LF2) by metagenomics to unravel the presence of hydrocarbon degraders. Moreover, we isolated Shinella zoogloeoides LFG9 and Bacillus swezeyi LFS15 from LF2 and combined them with Pseudomonas guguanensis SGPP2 isolated from an auto mechanic workshop soil to form the mixed consortium COG1. Bacterial isolates were tested for biosurfactant production. Additionally, the bioremediation potential of COG1 was studied as free and entrapped consortia by gas chromatography-mass spectrometry, in comparison to the single strains. Results revealed the presence of Actinobacteria (66.11%), Proteobacteria (32.21%), Gammaproteobacteria (5.39%), Actinomycetales (65.15%), Burkholderiales (13.92%), and Mycobacterium (32.22%) taxa, indicating the presence of hydrocarbon degraders in soil LF2. All three isolated strains were biosurfactant producers capable of degrading crude oil components within 14 days. However, Shinella zoogloeoides LFG9 performed best and was retained as candidate for further bioremediation investigation. In addition, COG1 performed better when immobilized, with entrapment effectiveness manifested by increased fatty acids and aromatic compound degradation. Attempt to improve crude oil biodegradation by adding surfactants failed as sodium dodecyl sulfate restrained the immobilized consortium performance.

A Computational Analysis of the Reaction of SO2 with Amino Acid Anions: Implications for Its Chemisorption in Biobased Ionic Liquids.

We report a series of calculations to elucidate one possible mechanism of SO2 chemisorption in amino acid-based ionic liquids. Such systems have been successfully exploited as CO2 absorbents and, since SO2 is also a by-product of fossil fuels' combustion, their ability in capturing SO2 has been assessed by recent experiments. This work is exclusively focused on evaluating the efficiency of the chemical trapping of SO2 by analyzing its reaction with the amino group of the amino acid. We have found that, overall, SO2 is less reactive than CO2, and that the specific amino acid side chain (either acid or basic) does not play a relevant role. We noticed that bimolecular absorption processes are quite unlikely to take place, a notable difference with CO2. The barriers along the reaction paths are found to be non-negligible, around 7-11 kcal/mol, and the thermodynamic of the reaction appears, from our models, unfavorable.

Parts-per-billion detection of carbon monoxide: A comparison between quartz-enhanced photoacoustic and photothermal spectroscopy.

We report on a comparison between two optical detection techniques, one based on a Quartz-Enhanced Photoacoustic Spectroscopy (QEPAS) detection module, where a quartz tuning fork is acoustically coupled with a pair of millimeter-sized resonator tubes; and the other one based on a Photothermal Spectroscopy (PTS) module where a Fabry-Perot interferometer acts as transducer to probe refractive index variations. When resonant optical absorption of modulated light occurs in a gas sample, QEPAS directly detects acoustic waves while PTS probes refractive index variations caused by local heating. Compact QEPAS and PTS detection modules were realized and integrated in a gas sensor system for detection of carbon monoxide (CO), targeting the fundamental band at 4.6 µm by using a distributed-feedback quantum cascade laser. Performance was compared and ultimate detection limits up to ∼ 6 part-per-billion (ppb) and ∼15 ppb were reached for QEPAS and the PTS module, respectively, using 100 s integration time and 40 mW of laser power.

Quartz-enhanced photoacoustic spectroscopy exploiting low-frequency tuning forks as a tool to measure the vibrational relaxation rate in gas species.

We demonstrated that quartz-enhanced photoacoustic spectroscopy (QEPAS) is an efficient tool to measure the vibrational relaxation rate of gas species, employing quartz tuning forks (QTFs) as sound detectors. Based on the dependence of the QTF resonance frequency on the resonator geometry, a wide range of acoustic frequencies with narrow detection bandwidth was probed. By measuring the QEPAS signal of the target analyte as well as the resonance properties of different QTFs as a function of the gas pressure, the relaxation time can be retrieved. This approach has been tested in the near infrared range by measuring the CH4 (nν4 ) vibrational relaxation rate in a mixture of 1% CH4, 0.15 % H2O in N2, and the H2O (ν1 ) relaxation rate in a mixture of 0.5 % H2O in N2. Relaxation times of 3.2 ms Torr and 0.25 ms Torr were estimated for CH4 and H2O, respectively, in excellent agreement with values reported in literature.

Fiber-Coupled Quartz-Enhanced Photoacoustic Spectroscopy System for Methane and Ethane Monitoring in the Near-Infrared Spectral Range.

We report on a fiber-coupled, quartz-enhanced photoacoustic spectroscopy (QEPAS) near-IR sensor for sequential detection of methane (CH4 or C1) and ethane (C2H6 or C2) in air. With the aim of developing a lightweight, compact, low-power-consumption sensor suitable for unmanned aerial vehicles (UAVs)-empowered environmental monitoring, an all-fiber configuration was designed and realized. Two laser diodes emitting at 1653.7 nm and 1684 nm for CH4 and C2H6 detection, respectively, were fiber-combined and fiber-coupled to the collimator port of the acoustic detection module. No cross talk between methane and ethane QEPAS signal was observed, and the related peak signals were well resolved. The QEPAS sensor was calibrated using gas samples generated from certified concentrations of 1% CH4 in N2 and 1% C2H6 in N2. At a lock-in integration time of 100 ms, minimum detection limits of 0.76 ppm and 34 ppm for methane and ethane were achieved, respectively. The relaxation rate of CH4 in standard air has been investigated considering the effects of H2O, N2 and O2 molecules. No influence on the CH4 QEPAS signal is expected when the water vapor concentration level present in air varies in the range 0.6-3%.

Mid-Infrared Quartz-Enhanced Photoacoustic Sensor for ppb-Level CO Detection in a SF6 Gas Matrix Exploiting a T-Grooved Quartz Tuning Fork.

An optical sensor for highly sensitive detection of carbon monoxide (CO) in sulfur hexafluoride (SF6) was demonstrated by using the quartz-enhanced photoacoustic spectroscopy technique. A spectrophone composed of a custom 8 kHz T-shaped quartz tuning fork with grooved prongs and a pair of resonator tubes, to amplify the laser-induced acoustic waves, was designed aiming to maximize the CO photoacoustic response in SF6. A theoretical analysis and an experimental investigation of the influence of SF6 gas matrix on spectrophone resonance properties for CO detection have been provided, and the performances were compared with the standard air matrix. A mid-infrared quantum cascade laser with a central wavelength at 4.61 µm, resonant with the fundamental band of CO, and an optical power of 20 mW was employed as the light excitation source. A minimum detection limit of 10 ppb at 10 s of integration time was achieved, and a sensor response time of ∼3 min was measured.

Light-induced thermo-elastic effect in quartz tuning forks exploited as a photodetector in gas absorption spectroscopy.

We report on a study of light-induced thermo-elastic effects occurring in quartz tuning forks (QTFs) when exploited as near-infrared light detectors in a tunable diode laser absorption spectroscopy sensor setup. Our analysis showed that when the residual laser beam transmitted by the absorption cell is focused on the QTF surface area where the maximum strain field occurs, the QTF signal-to-noise ratio (SNR) is proportional to the strain itself and to the QTF accumulation time. The SNR was also evaluated when the pressure surrounding the QTF was lowered from 700 Torr to 5 Torr, resulting in an enhancement factor of ∽4 at the lowest pressure. At 5 torr, the QTF employed as light detector showed an SNR ∽6.5 times higher than that obtained by using a commercially available amplified photodetector.

Photoacoustic spectroscopy for gas sensing: A comparison between piezoelectric and interferometric readout in custom quartz tuning forks.

We report on a comparison between piezoelectric and interferometric readouts of vibrations in quartz tuning forks (QTFs) when acting as sound wave transducers in a quartz-enhanced photoacoustic setup (QEPAS) for trace gas detection. A theoretical model relating the prong vibration amplitude with the QTF prong sizes and electrical resistance is proposed. To compare interferometric and piezoelectric readouts, two QTFs have been selected; a tuning fork with rectangular-shape of the prongs, having a resonance frequency of 3.4 kHz and a quality-factor of 4,000, and a QTF with prong having a T-shape characterized by a resonance frequency of 12.4 kHz with a quality-factor of 15,000. Comparison between the interferometric and piezoelectric readouts were performed by using both QTFs in a QEPAS sensor setup for water vapor detection. We demonstrated that the QTF geometry can be properly designed to enhance the signal from a specific readout mode.

Acoustic Coupling between Resonator Tubes in Quartz-Enhanced Photoacoustic Spectrophones Employing a Large Prong Spacing Tuning Fork.

A theoretical model describing the acoustic coupling between two resonator tubes in spectrophones exploiting custom-made quartz tuning forks (QTFs) is proposed. The model is based on an open-end correction to predict the optimal tube length. A calculation of the sound field distribution from one tube exit allowed for the estimation of the optimal radius as a function of the QTF prong spacing and the sound wavelength. The theoretical predictions have been confirmed using experimental studies employing a custom QTF with a fundamental flexural mode resonance frequency of 15.8 kHz and a quality factor of 15,000 at atmospheric pressure. The spacing between the two prongs was 1.5 mm. Spectrophones mounting this QTF were implemented for the quartz-enhanced photoacoustic detection of water vapor in air in the mid-infrared spectral range.