Microscale Thermophoresis and Molecular Modelling to Explore the Chelating Drug Transportation in the Milk to Infant

The microscale thermophoresis (MST) technique was utilized to investigate lactoferrin–drug interaction with the iron chelator, deferiprone, using label-free system. MST depends on the intrinsic fluorescence of one interacting partner. The results indicated a significant interaction between lactoferrin and deferiprone. The estimated binding constant for the lactoferrin–deferiprone interaction was 8.9 × 10⁻⁶ ± 1.6, SD, which is to be reported for the first time. Such significant binding between lactoferrin and deferiprone may indicate the potentiation of the drug secretion into a lactating mother’s milk. The technique showed a fast and simple approach to study protein–drug interaction while avoiding complicated labeling procedures. Moreover, the binding behavior of deferiprone within the binding sites of lactoferrin was investigated through molecular docking which reflected that deferiprone mediates strong hydrogen bonding with ARG121 and ASP297 in pocket 1 and forms H-bond and ionic interaction with ASN640 and ASP395, respectively, in pocket 2 of lactoferrin. Meanwhile, iron ions provide ionic interaction with deferiprone in both of the pockets. The molecular dynamic simulation further confirmed that the binding of deferiprone with lactoferrin brings conformational changes in lactoferrin that is more energetically stable. It also confirmed that deferiprone causes positive correlation motion in the interacting residues of both pockets, with strong negative correlation motion in the loop regions, and thus changes the dynamics of lactoferrin. The MM-GBSA based binding free energy calculation revealed that deferiprone exhibits ∆G TOTAL of −63,163 kcal/mol in pocket 1 and −63,073 kcal/mol in pocket 2 with complex receptor–ligand difference in pocket 1 and pocket 2 of −117.38 kcal/mol and −111.54 kcal/mol, respectively, which in turn suggests that deferiprone binds more strongly in the pocket 1. The free energy landscape of the lactoferrin–deferiprone complex also showed that this complex remains in a high energy state that confirms the strong binding of deferiprone with the lactoferrin. The current research concluded that iron-chelating drugs (deferiprone) can be transported from the mother to the infant in the milk because of the strong attachment with the lactoferrin active pockets.     

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds’ complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70–80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40–60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography–mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.     

Solubility Optimization of Loxoprofen as a Nonsteroidal Anti-Inflammatory Drug: Statistical Modeling and Optimization

Industrial-based application of supercritical CO₂ (SCCO₂) has emerged as a promising technology in numerous scientific fields due to offering brilliant advantages, such as simplicity of application, eco-friendliness, and high performance. Loxoprofen sodium (chemical formula C₁₅H₁₈O₃) is known as an efficient nonsteroidal anti-inflammatory drug (NSAID), which has been long propounded as an effective alleviator for various painful disorders like musculoskeletal conditions. Although experimental research plays an important role in obtaining drug solubility in SCCO₂, the emergence of operational disadvantages such as high cost and long-time process duration has motivated the researchers to develop mathematical models based on artificial intelligence (AI) to predict this important parameter. Three distinct models have been used on the data in this work, all of which were based on decision trees: K-nearest neighbors (KNN), NU support vector machine (NU-SVR), and Gaussian process regression (GPR). The data set has two input characteristics, P (pressure) and T (temperature), and a single output, Y = solubility. After implementing and fine-tuning to the hyperparameters of these ensemble models, their performance has been evaluated using a variety of measures. The R-squared scores of all three models are greater than 0.9, however, the RMSE error rates are 1.879 × 10⁻⁴, 7.814 × 10⁻⁵, and 1.664 × 10⁻⁴ for the KNN, NU-SVR, and GPR models, respectively. MAE metrics of 1.116 × 10⁻⁴, 6.197 × 10⁻⁵, and 8.777 × 10⁻⁵errors were also discovered for the KNN, NU-SVR, and GPR models, respectively. A study was also carried out to determine the best quantity of solubility, which can be referred to as the (x₁ = 40.0, x₂ = 338.0, Y = 1.27 × 10⁻³) vector.     

Effect of Erosive Agents on Surface Characteristics of Nano-Fluorapatite Ceramic: An In-Vitro Study

Erosive beverages cause dissolution of natural teeth and intra-oral restorations, resulting in surface characteristic changes, particularly roughness and degradation. The purpose of this study was to evaluate the surface roughness and topography of a dental ceramic following immersion in locally available erosive solutions. A total of 160 disc specimens of a nano-fluorapatite type ceramic (12 mm diameter and 2 mm thickness) were fabricated and equally distributed into two groups (n = 80) and then evenly distributed among the following five testing groups (n = 16): lemon juice, citrate buffer solution, 4% acetic acid, soft cola drink, and distilled water which served as a control. The surface roughness (Ra) and topography were evaluated using a profilometer and scanning electron microscope at baseline, 24 h, 96 h, and 168 h respectively. Data were analyzed using ANOVA and Tukey’s multiple comparisons (p ≤ 0.05). Surface changes were observed upon exposure to all acidic beverages except distilled water. Amongst all immersion media, 4% acetic acid produced the most severe surface roughness across all time periods (i.e., baseline, 24 h, 96 h, and 168 h). A statistically significant difference in the surface roughness values between all immersion media and across all four time intervals was observed. Erosive agents had a negative effect on the surface roughness and topography of the tested ceramic. The surface roughness increased with increased storage time intervals.     

Development,In-Vitro Characterization and Preclinical Evaluation of Esomeprazole-Encapsulated Proniosomal Formulation for the Enhancement of Anti-Ulcer Activity

Objective: The present study aimed to develop and optimize esomeprazole loaded proniosomes (EZL-PNs) to improve bioavailability and therapeutic efficacy. Method: EZL-PNs formulation was developed by slurry method and optimized by 33 box-Bhekhen statistical design software. Span 60 (surfactant), cholesterol, EZL concentration were taken as independent variables and their effects were evaluated on vesicle size (nm), entrapment efficiency (%, EE) and drug release (%, DR). Furthermore, optimized EZL-PNs (EZL-PNs-opt) formulation was evaluated for ex vivo permeation, pharmacokinetic and ulcer protection activity. Result: The EZL-PNs-opt formulation showed 616 ± 13.21 nm of vesicle size, and 81.21 ± 2.35% of EE. EZL-PNs-opt exhibited negative zeta potential and spherical confirmed scanning electron microscopy. EZL-PNs-opt showed sustained release of EZL (95.07 ± 2.10% in 12 h) than pure EZL dispersion. The ex-vivo gut permeation result exhibited a significantly (p < 0.05) enhanced flux than pure EZL. The in vivo results revealed 4.02-fold enhancement in bioavailability and 61.65% protection in ulcer than pure EZL dispersion (43.82%). Conclusion: Our findings revealed that EZL-PNs formulation could be an alternative delivery system of EZL to enhance oral bioavailability and antiulcer activity.     

Preparation of nano-hydroxyapatite/poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) biocomposite microspheres

Nano-hydroxyapatite (HA)/poly(l-lactide) (PLLA) composite microspheres with relatively uniform size distribution were prepared by a solid-in-oil-in-water (s/o/w) emusion solvent evaporation method. The encapsulation of the HA nanopaticles in microshperes was significantly improved by grafting PLLA on the surface of the HA nanoparticles (p-HA) during emulsion process. This procedure gave a possibility to obtain p-HA/PLLA composite microspheres with uniform morphology and the encapsulated p-HA nanoparticle loading reached up to 40 wt% (33 wt% of pure HA) in the p-HA/PLLA composite microspheres. The microstructure of composite microspheres from core-shell to single phase changed with the variation of p-HA to PLLA ratios. p-HA/PLLA composite microspheres with the diameter range of 2–3 μm were obtained. The entrapment efficiency of p-HA in microspheres could high up to 90 wt% and that of HA was only 13 wt%. Surface and bulk characterizations of the composite microspheres were performed by measurements such as wide angle X-ray diffraction (WAXD), thermal gravimetric analysis (TGA), environmental scanning electron microscope (ESEM) and transmission electron microscopy (TEM).     

Preparation and Photocatalytic Performance of TiO2 Nanowire-Based Self-Supported Hybrid Membranes

Nowadays, the use of hybrid structures and multi-component materials is gaining ground in the fields of environmental protection, water treatment and removal of organic pollutants. This study describes promising, cheap and photoactive self-supported hybrid membranes as a possible solution for wastewater treatment applications. In the course of this research work, the photocatalytic performance of titania nanowire (TiO₂ NW)-based hybrid membranes in the adsorption and degradation of methylene blue (MB) under UV irradiation was investigated. Characterization techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffractometry (XRD) were used to study the morphology and surface of the as-prepared hybrid membranes. We tested the photocatalytic efficiency of the as-prepared membranes in decomposing methylene blue (MB) under UV light irradiation. The hybrid membranes achieved the removal of MB with a degradation efficiency of 90% in 60 min. The high efficiency can be attributed to the presence of binary components in the membrane that enhanced both the adsorption capability and the photocatalytic ability of the membranes. The results obtained suggest that multicomponent hybrid membranes could be promising candidates for future photocatalysis-based water treatment technologies that also take into account the principles of circular economy.     

Selective hydroaminomethylation of olefins using simple and efficient Rh–phosphinite complex catalyst

Hydroaminomethylation of various olefins with primary and secondary amines was carried out using a simple and efficient rhodium–phosphinite complex catalyst. The influence of various reaction parameters including the effects of temperature, pressure, catalyst loading, time and solvents has been investigated. The present protocol is general with wider substrate applicability for the synthesis of an important class of aliphatic amines and arylethylamines. High activity and selectivity for amines was achieved with a very good substrate/catalyst molar ratio (turnover number 2500) under mild reaction conditions. Copyright © 2013 John Wiley & Sons, Ltd.