Effects of Chemical Modification on the Structure and Biological Activities of Polysaccharides Extracted from Inonotus Obliquus by Microwave.

A novel polysaccharide, Inonotus obliquus polysaccharide (IOP), was extracted using a microwave extraction method and subsequently subjected to modifications through sulfation, carboxymethylation, phosphorylation, and acetylation. Its physical and chemical properties were analyzed using various chemical techniques, including high-pressure liquid chromatography, ultraviolet light, Fourier-transform infrared spectroscopy, X-ray diffraction, Congo red test, and scanning electron microscopy. The antioxidant capacity was assessed using DPPH, ABTS, and hydroxyl radical assays, as well as by measuring the reducing power. Additionally, hypoglycemic activity was evaluated through α-glucosidase and α-amylase assays. The results indicated that the chemical modifications effectively altered the physical and chemical properties, as well as the biological activities of IOP. Compared to the unmodified IOP, the derivatives exhibited reduced sugar content, uronic acid content, and molecular weight, while demonstrating varying levels of antioxidant and hypoglycemic capabilities. Notably, the carboxymethylated IOP (IOP-C) displayed lower molecular weight, higher ABTS free radical scavenging rate, greater reducing ability, and increased α-amylase inhibition rate. Therefore, IOP-C shows promise as a potential edible antioxidant and hypoglycemic agent.

Incorporation of Complexation into a Coamorphous System Dramatically Enhances Dissolution and Eliminates Gelation of Amorphous Lurasidone Hydrochloride.

As a BCS II drug, the atypical antipsychotic agent lurasidone hydrochloride (LH) has low oral bioavailability mainly because of its poor aqueous solubility/dissolution. Unexpectedly, amorphous LH exhibited a much lower dissolution than that of its stable crystalline form arising from its gelation during the dissolution process. In the current study, a supramolecular coamorphous system of LH with l-cysteine hydrochloride (CYS) was prepared and characterized by powder X-ray diffraction and differential scanning calorimetry. Surprisingly, in comparison to crystalline and amorphous LH, such a coamorphous system dramatically enhanced solubility (at least ∼50-fold in the physiological pH range) and dissolution (∼1200-fold) of LH, and exhibited superior physical stability under long-term storage condition. More importantly, the coamorphous system was able to eliminate gelation of amorphous LH during dissolution. In order to further explore the mechanism of such improvement, the internal interactions of the coamorphous system in the solid state and in aqueous solution were investigated. Fourier transform infrared spectroscopy, Raman spectroscopy, and solid-state 13C NMR suggested that intermolecular hydrogen bonds formed between the nitrogen atom in the benzisothiazole ring of LH and the NH3+ group of CYS after coamorphization. A fluorescence quenching test with a Stern-Volmer plot and density functional theory modeling, phase-solubility study, and NMR test in D2O indicated that ground-state complexation occurred between LH and CYS in aqueous solution, which contributed to the solubility and dissolution enhancement of LH. The current study offers a promising strategy to overcome poor solubility/dissolution and be able to eliminate gelation of amorphous materials by coamorphization and complexation.

Improving Tabletability of Excipients by Metal-Organic Framework-Based Cocrystallization: a Study of Mannitol and CaCl2.

PURPOSE: To improve tabletability of pharmaceutical excipient mannitol by forming cocrystal with metal-organic framework (MOF) structure. METHODS: Mannitol was cocrystallized with CaCl2 by slurry method and solvent evaporation method. The obtained cocrystal was characterized by SCXRD, PXRD, and thermal analysis. Comparative study on tabletability between cocrystal and ß-mannitol were then conducted. Differences in tabletability were subsequently analyzed using the bonding area-bonding strength (BA-BS) model and correlated with their crystal structures. RESULTS: The prepared cocrystal contains mannitol, CaCl2 and water in molar ratio of 1:1:2 (i.e. mannitol·CaCl2·2H2O) and all the Ca2+ in the cocrystal are linked together by mannitol molecules through an infinite coordination network, demonstrating a typical MOF structure. Compared with ß-mannitol, such MOF-based cocrystal showed improved tabletability (~2-fold increased tensile strength) and reduced lamination tendency (~3-fold increased minimum compaction pressure to occur lamination). The tabletability improvement of cocrystal was dominated by its higher BS, which is attributed to stronger intermolecular interactions. The reduced lamination tendency was attributed to its lower in-die elastic recovery than ß-mannitol. CONCLUSIONS: MOF-based cocrystallization will be a promising and valuable approach to tailor mechanical properties of pharmaceutical materials in order to achieve better pharmaceutical performance.

Gel Formation Induced Slow Dissolution of Amorphous Indomethacin.

PURPOSE: Amorphous indomethacin (IMC) forms gel with a decreased dissolution behavior compared to crystalline IMC during dissolution. The current study aims to explore gelation mechanism and attempt to eliminate gelling effect by formulation development. METHODS: Amorphous IMC was prepared by melt-quenching method. Dissolution tests of amorphous IMC were performed at various temperatures under sink condition. The formed gels were characterized by PLM, SEM, DSC and XRPD. RESULTS: Amorphous IMC exhibited an initial higher dissolution followed by a decreased dissolution lower than its crystalline counterpart at 32 and 37°C, and even a much lower dissolution during the whole dissolution period at 45°C. Meanwhile, a viscous soft mass ("gel") was observed to adhere upon the paddle or wall of the vessel. The formed gel could be characterized as a three-dimensional dense micro-fiber structure under SEM. The gel formation was proposed to be related to the decreased Tg of amorphous IMC when contacting aqueous medium, resulting in entering into supercooled liquid state with high viscosity. The addition of hydrophilic silica accelerated gel formation, while mixing with hydrophobic silica was able to weaken and even eliminate the gelation, and hence significantly enhancing dissolution. CONCLUSIONS: The present study recommends that gel formation should be included in the investigation of amorphous materials in order to find ways for resolving defects of amorphous materials while keeping their advantages in pharmaceutics.

18F-FDG PET/CT metabolism multi-parameter prediction of chemotherapy efficacy in locally progressive gastric cancer.

PURPOSE: This study aimed to use an 18F-FDG PET/CT multiparametric quantitative analysis to determine the efficacy of neoadjuvant chemotherapy in patients with locally progressive gastric cancer. MATERIALS AND METHODS: We conducted a retrospective analysis of 34 patients with pathologically identified gastric cancer who received neoadjuvant chemotherapy and surgery. Chemotherapy regimens were followed and 18F-FDG PET/CT was conducted. We ascertained multiparamaters of the target lesions pre- and post-treatment and determined the ideal cutoff values for the percentage change in biomarkers. Independent factors were evaluated using binary logistic regression. A response classification system was used to explore the association between metabolic and anatomical responses and the degree of pathological remission. RESULTS: Binary logistic regression analysis showed that Lauren bowel type and change in total lesion glycolysis >45.2% were risk predictors for the efficacy of neoadjuvant chemotherapy; total lesion glycolysis demonstrated the best predictive efficacy. The categorical variable system of the two-module response (metabolic and anatomical response) group had a higher predictive accuracy than that of the single-module response (metabolic or anatomical response) group. CONCLUSIONS: Using 18F-FDG PET/CT multiparametric quantitative analysis, Lauren bowel type and change in total lesion glycolysis >45.2% were independent predictors of the efficacy of neoadjuvant chemotherapy in patients with gastric adenocarcinoma. Additionally, the dual-module assessment demonstrated high predictive efficacy.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

Surface activation of graphene oxide nanosheets by ultraviolet irradiation for highly efficient anti-bacterials.

A comprehensive investigation of anti-bacterial properties of graphene oxide (GO) and ultraviolet (UV) irradiated GO nanosheets was carried out. Microscopic characterization revealed that the GO nanosheet-like structures had wavy features and wrinkles or thin grooves. Fundamental surface chemical states of GO nanosheets (before and after UV irradiation) were investigated using x-ray photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. Minimum inhibitory concentration (MIC) results revealed that UV irradiated GO nanosheets have more pronounced anti-bacterial behavior than GO nanosheets and standard antibiotic, kanamycin. The MIC of UV irradiated GO nanosheets was 0.125 µg ml⁻¹ for Escherichia coli and Salmonella typhimurium, 0.25 µg ml⁻¹ for Bacillus subtilis and 0.5 µg ml⁻¹ for Enterococcus faecalis, ensuring its potential as an anti-infective agent for controlling the growth of pathogenic bacteria. The minimum bactericidal concentration of normal GO nanosheets was determined to be two-fold higher than its corresponding MIC value, indicating promising bactericidal activity. The mechanism of anti-bacterial action was evaluated by measuring the enzymatic activity of ß-D-galactosidase for the hydrolysis of o-nitrophenol-ß-D-galactopyranoside.

A novel drug-drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide.

Tadalafil and repaglinide, categorized as BCS class II drugs, have low oral bioavailabilities due to their poorly aqueous solubilities and dissolutions. The aim of this study was to enhance the dissolution of tadalafil and repaglinide by co-amorphization technology and evaluate the storage and compression stability of such coamorphous system. Based on Flory-Huggins interaction parameter (χ ≤ 0) and Hansen solubility parameter (δ t ≤ 7 MPa0.5) calculations, tadalafil and repaglinide was predicted to be well miscible with each other. Coamorphous tadalafil-repaglinide (molar ratio, 1 : 1) was prepared by solvent-evaporation method and characterized with respect to its thermal properties, possible molecular interactions. A single T g (73.1 °C) observed in DSC and disappearance of crystallinity in PXRD indicated the formation of coamorphous system. Principal component analysis of FTIR in combination with Raman spectroscopy and Ss 13C NMR suggested the absence of intermolecular interactions in coamorphous tadalafil-repaglinide. In comparison to pure crystalline forms and their physical mixtures, both drugs in coamorphous system exhibited significant increases in intrinsic dissolution rate (1.5-3-fold) and could maintain supersaturated level for at least 4 hours in non-sink dissolution. In addition, the coamorphous tadalafil-repaglinide showed improved stability compared to the pure amorphous forms under long-term stability and accelerated storage conditions as well as under high compressing pressure. In conclusion, this study showed that co-amorphization technique is a promising approach for improving the dissolution rate of poorly water-soluble drugs and for stabilizing amorphous drugs.