Influence of basil oil extract on the antioxidant and antifungal activities of nanostructured carriers loaded with nystatin

The combination of basil oil, natural antifungal, and nystatin has the potential to prevent the extension of topical fungal infections towards systemic infections. The aim of this study was to develop formulations based on basil oil and nystatin with the desired antifungal and antioxidant activity and low toxicity by using lipid nanocarriers. The synthesized nanocarriers showed spherical and homogeneous particles with main diameters less than 150 nm, as determined by TEM. The scanning calorimetric study revealed an imperfect crystallization in the core of lipid nanocarriers. Quantitative results suggested that basil oil concentration affects encapsulation efficiency. The prepared nanocarriers guaranteed an increased nystatin encapsulation by using 3% basil oil content. Chemiluminescence assay proved that the protective activity against oxygen free radicals was influenced by nystatin concentration. The in vitro antifungal studies revealed a better activity of the nanocarriers loaded with 1% nystatin in comparison with 0.5% loading.     

Dynamics of excitons and carriers at the NPB/C60 interface by transient photocurrents

The transient photocurrent (TPC) technique was performed to explore the dynamics of excitons and carriers at organic active layer/buffer layer interfaces. A special device with ITO/PEIE/NPB/C₆₀/Al structure was designed to study the interfacial processes at the NPB/C₆₀ interface. An external electrical field was provided to neutralize the built-in electrical field of the device. Interestingly, a new phenomenon was observed, wherein the polarity of the TPC changed from negative to positive under an external electrical field. The initial negative signal was ascribed to exciton separation by the built-in field in C₆₀, and the subsequent positive signal can be attributed to the diffusion of electrons that accumulate at the NPB/C₆₀ interface. TPC measurements shown that further increasing the external electrical field causes polarity to change twice. Analyzing the two changes in polarity revealed that the NPB did not only extract holes from C₆₀ but also provided an effective interface for exciton dissociation.     

中国聚变工程实验堆水冷包层钢构件流道成形控制研究

针对CFETR水冷包层流道钢构件热等静压制备时易变形压塌问题，利用单轴扩散焊设备开展了焊接工艺参数优化试验。在此基础上，重新设计了流道焊接界面位置和尺寸，用两步热等静压扩散焊法制备出了流道变形可控的平板型第一壁钢构件模块。优化试验表明，低活化钢试样的固相扩散焊温度需高于950℃，焊后经过760℃/60min回火热处理试样力学性能可以得到有效回复。     

Low‐Fouling Electrosprayed Hemoglobin Nanoparticles with Antioxidant Protection as Promising Oxygen Carriers

Despite all the attempts to create advanced hemoglobin (Hb)‐based oxygen carriers (HBOCs) employing an encapsulation platform, major challenges including attaining a high Hb loading and long circulation times still need to be overcome. Herein, the fabrication, for the first time, of nanoparticles fully made of Hb (Hb‐NPs) employing the electrospray technique is reported. The Hb‐NPs are then coated by antioxidant and self‐polymerized poly(dopamine) (PDA) to minimize the conversion of Hb into nonfunctional methemoglobin (metHb). The PDA shell is further functionalized with poly(ethylene glycol) (PEG) to achieve stealth properties. The results demonstrate that the as‐prepared Hb‐NPs are hemo‐ and biocompatible while offering antioxidant protection and decreasing the formation of metHb. Additionally, decoration with PEG results in decreased protein adsorption onto the Hb‐NPs surface, suggesting a prolonged retention time within the body. Finally, the Hb‐NPs also preserve the reversible oxygen‐binding and releasing properties of Hb. All in all, within this study, a novel HBOCs with high Hb content is fabricated and its potential as an artificial blood substitute is evaluated.     

Direct synthesis of Poly(Ԑ-Caprolactone)-block-poly (glycidyl methacrylate) copolymer and its usage as a potential nano micelles carrier for hydrophobic drugs

Ring-opening (ROP) and enzymatic copolymerization (ECP) are among the most widely used approaches for synthesizing copolymers of polycaprolactone (PCL). It involves multiple-step reactions and the utilization of enzymes that make the process a lot more complicated, time consuming, and expensive. Atom transfer radical polymerization (ATRP) has been adopted to synthesize a novel amphiphilic copolymer in our study. The study presents a method to eliminate the ROP/ECP multiple steps in monomer polymerization thus making the process simpler and smoother. The synthesis of cationic polymer micelles copolymer of PCL-PGMA (polycaprolactone grafted poly glycidyl methacrylate) was carried out using direct functionalization of hydroxy group in crude PCL to achieve a higher degree of functionalization, i.e., 12.8% for macroinitiator. FTIR and ¹H-NMR confirmed the successful synthesis of the copolymer with better control over the molecular weight with a PDI (1.84). DSC and XRD results showed the reduction of crystallinity by 86.81%, making copolymer more compatible for drug delivery application. The synthesized copolymer was further converted to nano-micelles drug carrier having an average size of 96.08 ± 21.22 nm. The drug encapsulation efficiency achieved was 60.0 ± 1.7%, and nano-micelles rendered a slow and controlled release of naproxen with long-term storage stability.     

Formulation of Cannabidiol in Colloidal Lipid Carriers

In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C.     

Taming of Singlet Oxygen: Towards Artificial Oxygen Carriers Based on 1,4-Dialkylnaphthalenes

Naphthalene endoperoxides are known as convenient sources of singlet oxygen (O₂, ¹Δ_g), which is the major product of endoperoxide cycloreversion reaction. However, their potential as carriers of ground-state molecular oxygen (O₂, ³Σ_g) similar to artificial oxygen carriers remains largely unexplored. This is due to the extreme reactivity and cytotoxic effects of the released singlet oxygen. We now report that a compound with a bimodular design, which incorporates an endoperoxide and an efficient physical quencher of singlet oxygen, 1,4-diazabicyclo[2.2.2]octane (DABCO), produces exclusively ground-state molecular oxygen. This result, coupled with the fact that oxygen release rates from endoperoxides are highly amenable to fine-tuning in a very broad range, and open to targeting by ligand attachment, raises the potential of these compounds far above any comparable chemical, or even biochemical sources. In cell culture experiments, we showed that the addition of the endoperoxide-quencher conjugate can enhance and sustain cell proliferation.     

pH‐Responsive Drug‐Delivery Systems

In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH‐Responsive drug‐delivery systems have attracted more and more interest as “smart” drug‐delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH‐responsive drug‐delivery systems; instead, it presents some recent progress obtained for pH‐responsive drug‐delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed.     

Disruption of redox catalytic functions of peroxiredoxin-thioredoxin complex in Mycobacterium tuberculosis H37Rv using small interface binding molecules

Mycobacterium tuberculosis has distinctive ability to detoxify various microbicidal superoxides and hydroperoxides via a redox catalytic cycle involving thiol reductants of peroxiredoxin (Prx) and thioredoxin (Trx) systems which has conferred on it resistance against oxidative killing and survivability within host. We have used computational approach to disrupt catalytic functions of Prx-Trx complex which can possibly render the pathogen vulnerable to oxidative killing in the host. Using protein–protein docking method, we have successfully constructed the Prx-Trx complex. Statistics of interface region revealed contact area of each monomer less than 1500 Å² and enriched in polar amino acids indicating transient interaction between Prx and Trx. We have identified ZINC40139449 as a potent interface binding molecule through virtual screening of drug-like compounds from ZINC database. Molecular dynamics (MD) simulation studies showed differences in structural properties of Prx-Trx complex both in apo and ligand bound states with regard to root mean square deviation (RMSD), radius of gyration (Rg), root mean square fluctuations (RMSF), solvent accessible surface area (SASA) and number of hydrogen bonds (NHBs). Interestingly, we found stability of two conserved catalytic residues Cys61 and Cys174 of Prx and conserved catalytic motif, WCXXC of Trx upon binding of ZINC40139449. The time dependent displacement study reveals that the compound is quite stable in the interface binding region till 30 ns of MD simulation. The structural properties were further validated by principal component analysis (PCA). We report ZINC40139449 as promising lead which can be further evaluated by in vitro or in vivo enzyme inhibition assays.