Plasma Exposure Research Articles

Near-Plasma Chemical Surface Engineering.

As a new trend in plasma surface engineering, plasma conditions that allow more-defined chemical reactions at the surface are being increasingly investigated. This is achieved by avoiding high energy deposition via ion bombardment during direct plasma exposure (DPE) causing destruction, densification, and a broad variety of chemical reactions. In this work, a novel approach is introduced by placing a polymer mesh with large open area close to the plasma-sheath boundary above the plasma-treated sample, thus enabling near-plasma chemistry (NPC). The mesh size effectively extracts ions, while reactive neutrals, electrons, and photons still reach the sample surface. The beneficial impact of this on the plasma activation of poly (tetrafluoroethylene) (PTFE) to enhance wettability and on the plasma polymerization of siloxanes, combined with the etching of residual hydrocarbons to obtain highly porous SiOx coatings at low temperatures, is discussed. Characterization of the treated samples indicates a predominant chemical modification yielding enhanced film structures and durability.

Using molecularly dissolved drug concentrations in PBBMs improves the prediction of oral absorption from supersaturating formulations

Predicting the absorption of drugs from enabling formulations is still challenging due to the limited capabilities of standard physiologically based biopharmaceutics models (PBBMs) to capture complex absorption processes. Amongst others, it is often assumed that both, molecularly and apparently dissolved drug in the gastrointestinal lumen are prone to absorption. A recently introduced method for measuring concentrations of molecularly dissolved drug in a dynamic in vitro dissolution setup using microdialysis has opened new opportunities to test this hypothesis and refine mechanistic PBBM approaches.In the present study, we compared results of PBBMs that used either molecularly or apparently dissolved concentrations in the simulated gastrointestinal lumen as input parameters. The in vitro dissolution data from three supersaturating formulations of Posaconazole (PCZ) were used as model input. The modeling outcome was verified using PCZ concentration vs. time profiles measured in human intestinal aspirates and in the blood plasma.When using apparently dissolved drug concentrations (i.e., the sum of colloid-associated and molecularly dissolved drug) the simulated systemic plasma exposures were overpredicted, most pronouncedly with the ASD-based tablet. However, if the concentrations of molecularly dissolved drug were used as input values, the PBBM resulted in accurate prediction of systemic exposures for all three PCZ formulations.The present study impressively demonstrated the value of considering molecularly dissolved drug concentrations as input value for PBBMs of supersaturating drug formulations.

Coherent X-ray Spectroscopy Elucidates Nanoscale Dynamics of Plasma-Enhanced Thin-Film Growth.

Sophisticated thin film growth techniques increasingly rely on the addition of a plasma component to open or widen a processing window, particularly at low temperatures. Taking advantage of continued increases in accelerator-based X-ray source brilliance, this real-time study uses X-ray Photon Correlation Spectroscopy (XPCS) to elucidate the nanoscale surface dynamics during Plasma-Enhanced Atomic Layer Deposition (PE-ALD) of an epitaxial indium nitride film. Ultrathin films are synthesized from repeated cycles of alternating self-limited surface reactions induced by temporally separated pulses of the material precursor and plasma reactant, allowing the influence of each on the evolving morphology to be examined. During the heteroepitaxial 3D growth examined here, sudden changes in the surface structure during initial film growth, consistent with numerous overlapping stress-relief events, are observed. When the film becomes continuous, the nanoscale surface morphology abruptly becomes long-lived with a correlation time spanning the period of the experiment. Throughout the growth experiment, there is a consistent repeating pattern of correlations associated with the cyclic growth process, which is modeled as transitions between different surface states. The plasma exposure does not simply freeze in a structure that is then built upon in subsequent cycles, but rather, there is considerable surface evolution during all phases of the growth cycle.

A strategy of accuracy quantification by extending the concentration monitoring coverage based on online double collision energy of ultra-high performance liquid chromatography tandem mass spectrometry: The pharmacokinetics of Toddalia asiatica as a case study

To facilitate the safety, efficacy and rationality of clinical application of traditional Chinese medicines (TCMs), pharmacokinetic research played an indispensable role. The key challenge during pharmacokinetic investigation lied at the substantial fluctuation of compound concentrations in the plasma over the course of absorption. Taking the pharmacokinetics of six compounds after administration of Toddalia asiatica (TA) as an example, an efficient strategy was established by introducing the online double collision energy (ODCE) into the quantification process applying ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). During the analytical program, double collision energy (DCE) was optimized to establish the dual calibration curve (DCC) with large concentration monitoring coverage (CMC) for meeting the wide content range of certain target compounds. Method validation test was performed in terms of linearity, precision, sensitivity, matrix effect, recovery, etc. The results displayed that the CMC of todarolactone with high exposure in plasma was extended from 1.25–2,500 ng/mL to 1.25–125,000 ng/mL. Furthermore, a rapid UHPLC-MS/MS method integrated with ODCE was successfully applied to the determination of six compounds in rat plasma, revealing an extremely high plasma concentration of todarolactone (16,662 ng/mL). This strategy could expand the range of quantification while retaining extraordinary sensitivity. Consequently, it could be a fit-for-purpose strategy to quantify compounds over a wide concentration range for in vivo process monitoring.

ISABELA Studies: Plasma Exposure and Target Engagement Do Not Explain the Lack of Efficacy of Ziritaxestat in Patients with Idiopathic Pulmonary Fibrosis.

Autotaxin (ATX) contributes to the production of lysophosphatidic acid (LPA), which is associated with fibrosis development in idiopathic pulmonary fibrosis (IPF). The ATX inhibitor ziritaxestat failed to reduce decline in forced vital capacity (FVC) in patients with IPF in ISABELA 1 and 2 (NCT03711162 and NCT03733444), two identically designed phase III studies. In the current analysis, we evaluated pharmacokinetic and pharmacodynamic data from the pooled ISABELA studies to determine whether the lack of efficacy could be attributed to insufficient exposure and/or target engagement. Nonlinear mixed effect modeling was performed to predict ziritaxestat exposure in individual patients and describe its effect on LPA C18:2 levels. We assessed whether there was a correlation between ziritaxestat and ATX concentration and evaluated the relationship between LPA C18:2 reduction and change from baseline in FVC. Ziritaxestat exposure in patients with IPF was numerically lower in those who received ziritaxestat on top of pirfenidone than in those who received ziritaxestat on top of nintedanib or ziritaxestat alone. In most patients, LPA C18:2 reduction was comparable to that reported in healthy volunteers. ATX concentrations increased over time and correlated weakly with ziritaxestat exposure and LPA C18:2 reduction. No correlation between reduction in LPA C18:2 and change from baseline in FVC was apparent. Based on these evaluations, exposure and target engagement are not thought to have contributed to the lack of efficacy observed. We hypothesize that the lack of efficacy of ziritaxestat in the ISABELA program, despite adequate LPA reduction, could be due to the involvement of an alternative pro-fibrotic pathway.

Correlation Between N-Demethyl Imatinib Trough Concentration and Serious Adverse Reactions in Patients with Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

Imatinib is the first-line treatment for gastrointestinal stromal tumors; however, the clinical prognosis and adverse reactions of patients vary owing to individualized discrepancies in plasma exposure. To determine the safe interval for steady-state plasma trough concentrations (C min ) of imatinib and its active metabolite, N-demethyl imatinib (NDI), 328 plasma samples from 273 patients treated with imatinib were retrospectively analyzed. Imatinib C min and NDI C min were tested, and adverse reactions were recorded. The association between imatinib C min , NDI C min , and serious adverse reactions was evaluated. The C min range of imatinib was 209.5-4950.0 ng/mL, with the mean value and SD of 1491.8 ± 731.4 ng/mL. The C min range of NDI was 80.0-2390.0 ng/mL with the mean value and SD of 610.8 ± 281.5 ng/mL. NDI C min was positively correlated with imatinib C min , whereas the ratio of NDI C min to imatinib C min (NDI C min /imatinib C min ) was negatively correlated with imatinib C min . Univariate logistic regression analysis demonstrated that the treatment objective, daily dose, imatinib C min , NDI C min , and imatinib C min + NDI C min were significantly associated with serious adverse reactions. Multivariate logistic regression analysis showed that NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. Monitoring NDI C min was beneficial for the rational application of imatinib and individualized treatment of patients with gastrointestinal stromal tumors.

New Imidazodiazepine Analogue, 5-(8-Bromo-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole, Provides a Simplified Synthetic Scheme, High Oral Plasma and Brain Exposures, and Produces Antiseizure Efficacy in Mice, and Antiepileptogenic Activity in Neural Networks in Brain Slices from a Patient with Mesial Temporal Lobe Epilepsy.

KRM-II-81 (1) is an imidazodiazepine GABAA receptor (GABAAR) potentiator with broad antiseizure efficacy and a low sedative burden. A brominated analogue, DS-II-73 (5), was synthesized and pharmacologically characterized as a potential backup compound as KRM-II-81 moves forward into development. The synthesis from 2-amino-5-bromophenyl)(pyridin-2yl)methanone (6) was processed in five steps with an overall yield of 38% and without the need for a palladium catalyst. GABAAR binding occurred with a Ki of 150 nM, and only 3 of 41 screened binding sites produced inhibition ≥50% at 10 μM, and the potency to induce cytotoxicity was ≥240 mM. DS-II-73 was selective for α2/3/5- over that of α1-containing GABAARs. Oral exposure of plasma and brain of rats was more than sufficient to functionally impact GABAARs. Tonic convulsions in mice and lethality induced by pentylenetetrazol were suppressed by DS-II-73 after oral administration and latencies to clonic and tonic seizures were prolonged. Cortical slice preparations from a patient with pharmacoresistant epilepsy (mesial temporal lobe) showed decreases in the frequency of local field potentials by DS-II-73. As with KRM-II-81, the motor-impairing effects of DS-II-73 were low compared to diazepam. Molecular docking studies of DS-II-73 with the α1β3γ2L-configured GABAAR showed low interaction with α1His102 that is suggested as a potential molecular mechanism for its low sedative side effects. These findings support the viability of DS-II-73 as a backup molecule for its ethynyl analogue, KRM-II-81, with the human tissue data providing translational credibility.

Single-Particle Spectroelectrochemistry: Promoting the Electrocatalytic Activity of Gold Nanorods via Oxygen Plasma Treatment without Structural Deformation.

Understanding of the electrocatalytic activity enhancement in gold nanoparticles is still limited. Herein, we present the effect of the oxygen plasma treatment on the electrochemical activity of gold nanorods (AuNRs). Oxygen plasma treatment resulted in the blueshift and line width narrowing of the localized surface plasmon resonance (LSPR) spectra obtained from individual AuNRs immobilized on an indium tin oxide (ITO) surface. These changes can be attributed to increases in the surface charges of the AuNRs. The formation of a Au-ITO heterojunction provided structural stability to the immobilized AuNRs regardless of the duration of oxygen plasma exposure. The electrocatalytic oxidation of hydrogen peroxide (H2O2) was induced by increases in the free-electron densities on the surfaces of these AuNRs owing to oxygen plasma treatment, and Au did not dissolve under the experimental conditions. However, the potential-dependent LSPR spectra of the individual AuNRs showed similar patterns of LSPR behavior, irrespective of the duration of oxygen plasma treatment and the concentration of H2O2. Therefore, this study based on single-particle spectroelectrochemistry and cyclic voltammetry improves the understanding of the role of oxygen plasma treatment in promoting the catalytic activity of structurally stable AuNRs immobilized on an ITO surface.

Plasma growth factors maintain constitutive translation in platelets to regulate reactivity and thrombotic potential

AbstractMechanisms of proteostasis in anucleate circulating platelets are unknown and may regulate platelet function. We investigated the hypothesis that plasma–borne growth factors/hormones (GFHs) maintain constitutive translation in circulating platelets to facilitate reactivity. Bio-orthogonal noncanonical amino acid tagging (BONCAT) coupled with liquid chromatography–tandem mass spectrometry analysis revealed constitutive translation of a broad-spectrum translatome in human platelets dependent upon plasma or GFH exposure, and in murine circulation. Freshly isolated platelets from plasma showed homeostatic activation of translation-initiation signaling pathways: phosphorylation of p38/ERK upstream kinases, essential intermediate MNK1/2, and effectors eIF4E/4E-BP1. Plasma starvation led to loss of pathway phosphorylation, but it was fully restored with 5-minute stimulation by plasma or GFHs. Cycloheximide or puromycin infusion suppressed ex vivo platelet GpIIb/IIIa activation and P-selectin exposure with low thrombin concentrations and low-to-saturating concentrations of adenosine 5′-diphosphate (ADP) or thromboxane analog but not convulxin. ADP–induced thromboxane generation was blunted by translation inhibition, and secondary-wave aggregation was inhibited in a thromboxane-dependent manner. Intravenously administered puromycin reduced injury-induced clot size in cremaster muscle arterioles, and delayed primary hemostasis after tail tip amputation but did not delay neither final hemostasis after subsequent rebleeds, nor final hemostasis after jugular vein puncture. In contrast, these mice were protected from injury-induced arterial thrombosis and thrombin-induced pulmonary thromboembolism (PE), and adoptive transfer of translation-inhibited platelets into untreated mice inhibited arterial thrombosis and PE. Thus, constitutive plasma GFH-driven translation regulates platelet G protein–coupled receptor reactivity to balance hemostasis and thrombotic potential.

Unleashing the Power of Plasma and Flow: A Novel Cold Plasma‐Oscillatory System for Enhanced Continuous Biodiesel Production from Sunflower Oil

While fossil fuel resources are limited, the increasing demand for energy in the industrial and transportation sectors has led to using renewable fuels. This study aims to improve biodiesel production from sunflower oil by combining cold plasma and oscillatory systems through a transesterification process. The four main operational variables are examined, such as molar ratio (MR) (1:6–1:12), catalyst concentration (CC) (0.5–1.25 wt%), plasma exposure time (PET) (25–75 s), and residence time (RT) (30–90 s). The smooth periodic constriction reactor's physical attributes, including the diameter of the tube (D), the diameter of the constricted region (d0), and the distance between baffles (l), as well as the properties of the cold plasma system, are determined. The data analysis presents that PET, RT, CC, and MR have the greatest effect on efficiency. This optimization indicates that by exposing the reaction mixture to plasma for 59.99 s, adding 1.09% by weight of the catalyst, and with a MR of 7.17 in 86.43 s, biodiesel with a conversion percentage of 94.75% is produced. The results show that the optimum point matches with EN 14214 standard.

Biopolymer-loaded plasma-mediated multi-functional finishes of polypropylene fabrics

Polypropylene (PP) has unique competitiveness with other synthetic fibers due to its suitable spinnability, availability of raw materials, and low processing cost. PP fabric exhibits excellent chemical, physical, and mechanical properties, such as a light texture, adequate tensile strength, and resistance to most chemicals. However, the absence of reactive functional groups in PP fiber, besides its high crystallinity, results in hydrophobic surface, low affinity to dyestuffs, and poor antistatic properties, which restrict its use in the clothing field. Herein, a water- and energy-saving, eco-friendly finish is proposed to render PP desired properties suitable for textile applications. The surface of PP fabric was activated using oxygen and nitrogen plasma radiations. The plasma-irradiated PP fabric was post-treated with two renewable eco-friendly proteinic biopolymers, namely gelatin and sericin, in the presence and absence of a crosslinking agent. The effects of different process conditions on the properties of the modified PP, including the duration of plasma exposure, the concentration of biopolymer, and treatment temperature were monitored. The affinity of the treated PP fabric towards anionic and cationic dyes was evaluated. The findings of this study demonstrated that the comfort attributes of the plasma/biopolymer-finished fabrics, such as the induced antistatic properties, wettability, and ultraviolet protection, were remarkably improved. The plasma-mediated biopolymer-finished PP fabrics were found dyeable with cationic and anionic dyes. The change in the chemical and morphological structures of PP fabrics was monitored using Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy.

Gas Plasma Exposure Alters Microcirculation and Inflammation during Wound Healing in a Diabetic Mouse Model.

Diabetes can disrupt physiological wound healing, caused by decreased levels or impaired activity of angiogenic factors. This can contribute to chronic inflammation, poor formation of new blood vessels, and delayed re-epithelialization. The present study describes the preclinical application of medical gas plasma to treat a dermal, full-thickness ear wound in streptozotocin (STZ)-induced diabetic mice. Gas plasma-mediated effects occurred in both sexes but with gender-specific differences. Hyperspectral imaging demonstrated gas plasma therapy changing microcirculatory parameters, particularly oxygen saturation levels during wound healing, presumably due to the gas plasma's tissue delivery of reactive species and other bioactive components. In addition, gas plasma treatment significantly affected cell adhesion by regulating focal adhesion kinase and vinculin, which is important in maintaining skin barrier function by regulating syndecan expression and increasing re-epithelialization. An anticipated stimulation of blood vessel formation was detected via transcriptional and translational increase of angiogenic factors in gas plasma-exposed wound tissue. Moreover, gas plasma treatment significantly affected inflammation by modulating systemic growth factors and cytokine levels. The presented findings may help explain the mode of action of successful clinical plasma therapy of wounds of diabetic patients.

Effect of Dry Etching to Improve Ohmic Contacts on Bulk, Lightly-Doped β-Ga2O3

Ti/Au is a typical Ohmic metal contact stack to n-type β-Ga2O3 but there have been few systematic studies of the use of pre-exposure of the surface to plasmas prior to metal deposition in order to lower the contact resistance. The effects of Cl2/Ar Inductively Coupled Plasma exposure of Ga2O3 surfaces prior to deposition of Ti/Au (20/80 nm) contacts were examined through circular transfer length method (CTLM) measurements to determine both the contact resistance and specific contact resistivity. ICP source power, which controls ion density in the plasma is found to be more important than ion energy (∼165–490 eV in these experiments). The plasma exposure improved specific contact resistivity by more than a factor of 2 in all cases for lightly n-type (1017 cm−3) Ga2O3 and a minimum value of 2 × 10−4 Ω.cm2 was obtained after heating at 550 °C.

Olgotrelvir, a dual inhibitor of SARS-CoV-2 Mpro and cathepsin L, as a standalone antiviral oral intervention candidate for COVID-19

Oral antiviral drugs with improved antiviral potency and safety are needed to address current challenges in clinical practice for treatment of COVID-19, including the risks of rebound, drug-drug interactions, and emerging resistance. Olgotrelvir (STI-1558) is designed as a next-generation antiviral targeting the SARS-CoV-2 main protease (Mpro), an essential enzyme for SARS-CoV-2 replication, and human cathepsin L (CTSL), a key enzyme for SARS-CoV-2 entry into host cells. Olgotrelvir is a highly bioavailable oral prodrug that is converted in plasma to its active form, AC1115. The dual mechanism of action of olgotrelvir and AC1115 was confirmed by enzyme activity inhibition assays and co-crystal structures of AC1115 with SARS-CoV-2 Mpro and human CTSL. AC1115 displayed antiviral activity by inhibiting replication of all tested SARS-CoV-2 variants in cell culture systems. Olgotrelvir also inhibited viral entry into cells using SARS-CoV-2 Spike-mediated pseudotypes by inhibition of host CTSL. In the K18-hACE2 transgenic mouse model of SARS-CoV-2-mediated disease, olgotrelvir significantly reduced the virus load in the lungs, prevented body weight loss, and reduced cytokine release and lung pathologies. Olgotrelvir demonstrated potent activity against the nirmatrelvir-resistant Mpro E166 mutants. Olgotrelvir showed enhanced oral bioavailability in animal models and in humans with significant plasma exposure without ritonavir. In phase I studies (ClinicalTrials.gov: NCT05364840 and NCT05523739), olgotrelvir demonstrated a favorable safety profile and antiviral activity. Olgotrelvir is an oral inhibitor targeting Mpro and CTSL with high antiviral activity and plasma exposure and is a standalone treatment candidate for COVID-19. Funded by Sorrento Therapeutics.

Surface hardening of structural steels ShKh15 and 40KhN2MA by pulsed plasma flows

The article is devoted to an innovative method of surface hardening of steels 40KhN2МА and ShKh15 by pulsed plasma flows. The treatment was carried out in a wide range of absorbed energy density from 20 to 100 J/cm2, with a plasma exposure duration of 1 ms. The results of a study of the structure, phase composition and morphology of the modified surface layer, as well as such characteristics as thickness, microhardness, surface roughness, and level of residual stresses are presented. The modified layer of steel contains several structural components with distinctive characteristics. The maximum thickness of the modified hardened layer was 125 µm. The conducted research made it possible to establish optimal treatment modes, characterized by an increase in surface microhardness by 3—4 times, a decrease in roughness by up to 35 % and the presence of compressive residual stresses, which opens up prospects for the development of highly effective technology for strengthening critical products.

Exploring inter-ethnic and inter-patient variability and optimal dosing of osimertinib: a physiologically based pharmacokinetic modeling approach.

Purpose: This study aimed to develop and validate a physiologically based pharmacokinetic (PBPK) model for osimertinib (OSI) to predict plasma trough concentration (Ctrough) and pulmonary EGFRm+ (T790M and L858R mutants) inhibition in Caucasian, Japanese, and Chinese populations. The PBPK model was also utilized to investigate inter-ethnic and inter-patient differences in OSI pharmacokinetics (PK) and determine optimal dosing regimens. Methods: Population PBPK models of OSI for healthy and disease populations were developed using physicochemical and biochemical properties of OSI and physiological parameters of different groups. And then the PBPK models were validated using the multiple clinical PK and drug-drug interaction (DDI) study data. Results: The model demonstrated good consistency with the observed data, with most of prediction-to-observation ratios of 0.8-1.25 for AUC, Cmax, and Ctrough. The PBPK model revealed that plasma exposure of OSI was approximately 2-fold higher in patients compared to healthy individuals, and higher exposure observed in Caucasians compared to other ethnic groups. This was primarily attributed to a lower CL/F of OSI in patients and Caucasian. The PBPK model displayed that key factors influencing PK and EGFRm+ inhibition differences included genetic polymorphism of CYP3A4, CYP1A2 expression, plasma free concentration (fup), albumin level, and auto-inhibition/induction on CYP3A4. Inter-patient PK variability was most influenced by CYP3A4 variants, fup, and albumin level. The PBPK simulations indicated that the optimal dosing regimen for patients across the three populations of European, Japanese, and Chinese ancestry was OSI 80mg once daily (OD) to achieve the desired range of plasma Ctrough (328-677nmol/L), as well as 80mg and 160mg OD for desirable pulmonary EGFRm+ inhibition (>80%). Conclusion: In conclusion, this study's PBPK simulations highlighted potential ethnic and inter-patient variability in OSI PK and EGFRm+ inhibition between Caucasian, Japanese, and Chinese populations, while also providing insights into optimal dosing regimens of OSI.

Long-term antifouling surfaces for urinary catheters.

The presence of a variety of bacteria is an inevitable/indispensable part of human life. In particular, for patients, the existence and spreading of bacteria lead to prolonged treatment period with many more complications. The widespread use of urinary catheters is one of the main causes for the prevalence of infections. The necessity of long-term use of indwelling catheters is unavoidable in terms of the development of bacteriuria and blockage. As is known, since a permanent solution to this problem has not yet been found, research and development activities continue actively. Herein, polyethylene glycol (PEG)-like thin films were synthesized by a custom designed plasma enhanced chemical vapor deposition (PE-CVD) method and the long-term effect of antifouling properties of PEG-like coated catheters was investigated against Escherichia coli and Proteus mirabilis. The contact angle measurements have revealed the increase of wettability with the increase of plasma exposure time. The antifouling activity of surface-coated catheters was analyzed against the Gram-negative/positive bacteria over a long-term period (up to 30 days). The results revealed that PE-CVD coated PEG-like thin films are highly capable of eliminating bacterial attachment on surfaces with relatively reduced protein attachment without having any toxic effect. Previous statements were supported with SEM, XPS, FTIR spectroscopy, and contact angle analysis.

Chemically robust superhydrophobic surfaces with a self‐replenishing nanoscale liquid coating

AbstractDue to poor chemical robustness, superhydrophobic surfaces become susceptible to failure, especially in a highly oxidative environment. To ensure the long‐term efficacy of these surfaces, a more stable and environmentally friendly coating is required to replace the conventional salinization layers. Here, soot‐templated surfaces with re‐entrant nanostructures are precoated with polydimethylsiloxane (PDMS) brushes. An additional nanometer‐thick lubricant layer of PDMS was then applied to increase chemical stability. The surface is superhydrophobic with a nanoscale liquid coating. Since the lubricant layer is thin, ridge formation is suppressed, which leads to low drop sliding friction and fast drop shedding. By introducing a bottom “reservoir” of a free lubricant as an oil source for self‐replenishing to the upper layer, the superhydrophobic surface becomes more stable and heals spontaneously in response to alkali erosion and O2 plasma exposure. This design also leads to a higher icing delay time and faster removal of impacting cooled water drops than for uncoated surfaces, preventing icing at low temperatures.

Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. Invitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUCinf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates.

Therapeutic drug monitoring of imatinib in patients with chronic myeloid leukaemia: Experience from Oran HUE

Imatinib, a first-line treatment for chronic myelogenous leukemia, presents significant interindividual pharmacokinetic variability. The correlation between the plasma exposure of Imatinib and its pharmacological effects makes this drug a good candidate for pharmacological therapeutic monitoring in addition to the usual monitoring tests. We introduced monitoring of Imatinib in 27 patients suffering from chronic myelogenous leukemia. According to the dosage results, dosage adaptation recommendations were proposed to clinicians in patients outside the targeted therapeutic range. The goal was to achieve an optimal response to Imatinib, prevent its adverse effects and improve adherence to treatment.