New formulation of ibuprofen on absorption-rate: A comparative bioavailability study in healthy volunteers.

BACKGROUND: Enteric-coated capsules are solid dosage forms which are designed to bypass the stomach and release the drug in the small intestine. This study was done to compare pharmacokinetics of ibuprofen tablet and ibuprofen as enteric-coated capsule using sodium alginate beads. METHODS: A crossover randomized study was performed on 12 healthy volunteers receiving a single dose of regular ibuprofen tablet (200 mg) and enteric-coated capsule (200 mg). The washout time between the periods was one month. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. High-performance liquid chromatography (HPLC) method used the following specifications: C18 column with 4.6 mm diameter & 25 mm length, the fluorescent detector of excitation and emission wavelengths were 224 and 290 nm, respectively. RESULTS: After a single oral dose of ibuprofen formulations, the median times to maximum concentration were 60 and 240 minutes in ibuprofen tablet (200 mg) and enteric-coated capsule, respectively. The maximum levels for the participants receiving ibuprofen tablet and enteric-coated capsule were 11.71±1.3 and 10.32±4.19 µg/mL, respectively. The pharmacokinetic (PK) modeling data showed the area under curve (AUC) to be 61.51 hours & 86.62 hours for the group receiving the tablet and the capsule, respectively. CONCLUSION: According to the results, in is concluded that enteric coating may delay the onset of ibuprofen effect and increases the duration of action. This formulation has advantages over the conventional drug delivery systems as it lengthens the dosing intervals and also increases patient compliance for chronic pain.

Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines.

BACKGROUND: Quercetin is a plant polyphenol from the flavonoid group that plays a fundamental role in controlling homeostasis due to its potent antioxidant properties. However, quercetin has extremely low water solubility, which is a major challenge in drug absorption. METHOD: In this study, we described a simple method for the synthesis of quercetin nanoparticles. The quercetin nanoparticles had an average diameter of 82 nm and prominent yellow emission under UV irradiation. Therefore, we used an in vitro model treated with quercetin and quercetin nanoparticles to investigate the effects of quercetin nanoparticles on MCF-7 breast cancer cell line. FINDING: MCF-7 cells were cultured with different concentrations (1-100 µM) of quercetin nanoparticles at the 24th, 48th and 72 nd hours, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In this study, we found that quercetin nanoparticles (1-100 µM) could significantly reduce cell vitality, growth rate and colony formation of MCF-7 cells. CONCLUSION: Quercetin nanoparticles can inhibit cell growth by blocking the cell cycle and promoting apoptosis in MCF-7 cells more than quercetin. As a result, quercetin nanoparticles may be useful therapy or prevention on breast cancer.

Nonylphenol induces liver toxicity and oxidative stress in rat.

BACKGROUND: Nonylphenol (NP) is one of the most widely used synthetic xenoestrogens in detergents, plastic products, paints and the most important environmental degradation factor. In this study, the effects NP was investigated on hepatic oxidative stress-related gene expression in rats. METHOD: Wistar male rats weighing 150-200 g were divided into control and NP receiving groups. NP was given in three doses (5, 25, and 125 µg/kg). All doses were given by gavage and the experiment continued for a consecutive 35 days. AST, ALT and ALP determined by the colorimetric method. The RNA was extracted from the rats liver tissue and RT- PCR was used to investigate the changes in gene expression. For this purpose, primers and specific probes of HO1 and Gadd45b genes as well as B-actin as control were prepared and the expression of each gene was separately assessed with ABI-7300. Hematoxylin and eosin staining was performed for evaluating of cell death. FINDING: The data from our study indicated nonylphenol increased alkaline phosphatase level but not changed aspartate aminotransferase and alanine aminotransferase in serum. That various doses of NP result in a dose-dependent increase in the expression of HO-1 gene. The intensified expression of HO-1 was statistically significant just at the doses of 25 and 125 µg/kg compared to control group (p < 0.05). In addition, it was shown that different doses of nonylphenol raised the expression of Gadd45b gene and this increase was significantly evident at 5 µg/kg (p < 0.05). Histological evaluation also indicated that NP increased hepatocytes cell death. CONCLUSION: We conclude that NP increased serum alkaline phosphatase, lead to liver damage and can increase the expression of HO1 and Gadd45b genes and may modify the toxic effects on liver through induction of oxidative stress.

Induction Effect of Bisphenol A on Gene Expression Involving Hepatic Oxidative Stress in Rat.

Background and Objective. Bisphenol A (BPA) is an abundantly used xenoestrogenic chemical which may cause various disorders in body. In the present study, we sought to investigate the effects of various doses of BPA on hepatic oxidative stress-related gene expression in rats. Methods. Male Wistar rats weighing 150-200 g were used in this study. Three doses of the BPA (5, 25, and 125 µg/kg) in corn oil were administered as gavage during 35 consecutive days. After the experiment, the rats were expired and the livers were removed and stored at -80°C freezer for RNA extraction. Findings. The Real Time PCR showed increased expression of HO-1 in the rats receiving BPA doses compared to the control group. This effect was dose-dependent and higher at doses of 25 and 125 µg/kg than 5 µg/kg of body weight (p < 0.05). It was also demonstrated that various doses BPA can increase GADD45B gene expression compared to control group. That expression was significantly dominant in the lowest dose (5 µg/kg) of the BPA (p < 0.05). The final body weights (168.0 ± 10.0 gr) in the treatment group [BPA (125 µg/kg)] showed a significant decrease compared to control group (191.60 ± 6.50 gr). Conclusion. These findings demonstrate that BPA generated ROS and increased the antioxidant gene expression that causes hepatotoxicity.