Determination of Regorafenib monohydrate (colorectal anticancer drug) solubility in supercritical CO2: Experimental and thermodynamic modeling.

In this study, the solubilities of Regorafenib monohydrate (REG), a widely used as a colorectal anticancer drug, in supercritical carbon dioxide (ScCO2) were measured under various pressures and temperature conditions, for the first time. The minimum value of REG in mole fraction was determined to be 3.06×10-7, while the maximum value was found to be 6.44×10-6 at 338 K and 27 MPa. The experimental data for REG were correlated through the utilization of two types of models: (1) a set of 25 existing empirical and semi-empirical models that incorporated 3-8 parameters according to functional dependencies, (2) a model that relied on solid-liquid equilibrium (SLE) and the newly improved association models. All of the evaluated models were capable of generating suitable fits to the solubility data of REG, however, the average absolute relative deviation (AARD) of Gordillo et al. model (AARD=13.2%) and Reddy et al. model (AARD=13.5%) indicated their superiority based on AARD%. Furthermore, solvation and sublimation enthalpies of REG drug were estimated for the first time.

Preparation and physicochemical characterization of N-succinyl chitosan-coated liposomes for oral delivery of grape seed extract and evaluation of its effect on pulmonary fibrosis induced by bleomycin in rats.

Objectives: This study aimed to develop an oral succinyl chitosan-coated liposomal formulation containing grape seed extract and assess its therapeutic efficacy in rats with bleomycin-induced pulmonary fibrosis. Materials and Methods: N-succinyl chitosan was synthesized, and the liposomal formulations were prepared and characterized regarding phenolic content assay and morphology. Size, zeta potential, in vitro drug release, and stability. Pulmonary fibrosis was induced by intratracheal bleomycin injection, and hydroxyproline measurements, lung weight, animal body weight, as well as histopathological studies were performed. Results: Succinyl chitosan increases the physical stability of the formulation, especially in acidic conditions. Drug release studies revealed that 66.27% of the loaded drug was released from CF2 in an acidic medium in 2 hr, but 92.31% of the drug was released in 8 hr in a pH=7 medium. An in vivo study demonstrated that rats exposed to bleomycin significantly lost weight, while those treated with CF2 (400 mg/kg) partially regained weight. Bleomycin treatment increased the mean lung weight and the amount of hydroxyproline in the lungs; these values were significantly decreased in the group treated with 400 mg/kg CF2 (P<0.05). Histopathological examination confirmed that treatment with 400 mg/kg CF2 improved lung fibrosis. Conclusion: In rats, oral administration of N-succinyl chitosan-coated liposomes containing grape seed extract at the 400 mg/kg dose ameliorates bleomycin-induced pulmonary fibrosis.

Effects of Ellagic Acid on Oxidative Stress Index, Inflammatory Markers and Quality of Life in Patients With Irritable Bowel Syndrome: Randomized Double-blind Clinical Trial.

Irritable bowel syndrome (IBS) is a common disorder that affects the large intestine. Oxidative stress and inflammation play a major role in IBS. Considering the antioxidant properties of ellagic acid (EA), this study was designed to evaluate the effect of EA on oxidative stress index, inflammatory markers, and quality of life in patients with IBS. This research was conducted as a randomized, double-blind, placebo-controlled clinical trial; 44 patients with IBS were recruited. Patients who met the inclusion criteria were randomly allocated to consume a capsule containing 180 mg of EA per day (n = 22) or a placebo (n = 22) for 8 weeks. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), C-reactive protein (CRP), and interleukin-6 (IL-6) were measured at the beginning and the end of the study. Also, quality of life was assessed using a self-report questionnaire for IBS patients (IBS-QOL). At the end of the study, we saw a significant decrease and increase in the MDA and TAC in the intervention group, respectively (p < 0.05). Also, EA consumption reduced CRP and IL-6 levels, and these changes were significant in comparison with placebo group changes (p < 0.05). The overall score of IBS-QOL significantly decreased, and quality of life was increased (p < 0.05), but there were no significant changes in the placebo group. According to these findings, receiving polyphenols, such as EA, may help maintain intestinal health by modulating inflammation and oxidative stress and ultimately improving the quality of life in IBS patients. Trial Registration: Iranian Registry of Clinical Trials Identifier: IRCT20141025019669N11.

Ascorbic Acid Significantly Decreases Creatine Kinase Plasma Levels in an Animal Model of Statin/Fibrate-Induced Myopathy.

BACKGROUND: Myopathy is one of the side effects of lipid-lowering drugs, especially statins and particularly when combined with a fibrate. To diagnose myopathy and determine its severity, the plasma levels of three enzymes, creatine kinase (CK), aldolase, and lactate dehydrogenase (LDH), are routinely measured. Physical exercise can aggravate the statin-associated muscular disease. The question is whether antioxidants like ascorbic acid (Vit. C) can prevent such myopathy. METHODS: In this experiment, a combination of atorvastatin (ATV, 80 mg/kg/day) and gemfibrozil (GMF, 1000 mg/kg/day) orally for 10 days as well as exercise as forced swimming on days 8, 9, and 10 were used to induce myopathy. Ascorbic acid (50 mg/kg/day, orally) was added to ATV/GMF plus exercise regimen throughout the 10 days in the treatment group. Mean blood levels of CK, aldolase, and LDH were measured in addition to swimming tolerance times. RESULTS: There was a significantly higher swimming tolerance time (P < 0.05) and lower CK levels (P < 0.01) in rats receiving ATV/GMF/Vit. C plus exercise compared with rats not taking Vit. C. LDH and aldolase did not decrease significantly. CONCLUSION: The results of this study showed that Vit. C can be effective in preventing myopathy caused by fat-lowering drugs.

Red Lentil Extract: Neuroprotective Effects on Perphenazine Induced Catatonia in Rats.

INTRODUCTION: Parkinsonism is a neurodegenerative disease that is defined by certain symptoms such as muscle rigidity, impaired movement, catatonia, tremor and disorientation of body. AIM: The aim was to investigate the effect of red lentil extract on perphenazine-induced Catatonia in model of rat. MATERIALS AND METHODS: This experimental study was done on 48 male albino rats (weight 180-200g) of the Sprague-Dawley strain. Animals were randomly divided into six groups and were pre-treated with a single dose of red lentil extract (200, 400, 800 and 1000 mg/kg), most effective dose of bromocriptine (30mg/kg) and normal saline (5ml/kg) via intraperitoneal (IP) route. perphenazine (5 mg/kg) was after 30 minutes, administered (IP) to induce catatonia. The scoring method of Morpurgo was used to determine the muscular rigidity of animals. RESULTS: The results showed that the 200mg/kg red lentil extract treated group had no significant reduction in catatonic responses after perphenazine administration in comparison with control group while the groups that received 800 and 1000mg/kg of red lentil extract showed significant difference (p<0.05) at all the time points. CONCLUSION: The results revealed that hydroalcoholic extract of red lentil has protective effect on Catatonia induced by perphenazine in rats. So this extract may be probably beneficial for catatonia in Parkinsonism.