Thymoquinone Glucuronide Conjugated Magnetic Nanoparticle for Bimodal Imaging and Treatment of Cancer as a Novel Theranostic Platform.

BACKGROUND: Theranostic oncology combines therapy and diagnosis and is a new field of medicine that specifically targets the disease by using targeted molecules to destroy the cancerous cells without damaging the surrounding healthy tissues. OBJECTIVE: We aimed to develop a tool that exploits enzymatic TQ release from glucuronide (G) for the imaging and treatment of lung cancer. We added magnetic nanoparticles (MNP) to enable magnetic hyperthermia and MRI, as well as 131I to enable SPECT imaging and radionuclide therapy. METHODS: A glucuronide derivative of thymoquinone (TQG) was enzymatically synthesized and conjugated with the synthesized MNP and then radioiodinated with 131I. New Zealand white rabbits were used in SPECT and MRI studies, while tumor modeling studies were performed on 6-7- week-old nude mice utilized with bioluminescence imaging. RESULTS: Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectra confirmed the expected structures of TQG. The dimensions of nanoparticles were below 10 nm and they had rather polyhedral shapes. Nanoparticles were radioiodinated with 131I with over 95% yield. In imaging studies, in xenograft models, tumor volume was significantly reduced in TQGMNP-treated mice but not in non-treated mice. Among mice treated intravenously with TQGMNP, xenograft tumor models disappeared after 10 and 15 days, respectively. CONCLUSION: Our findings suggest that TQGMNP in solid, semi-solid and liquid formulations can be developed using different radiolabeling nuclides for applications in multimodality imaging (SPECT and MRI). By altering the characteristics of radionuclides, TQGMNP may ultimately be used not only for diagnosis but also for the treatment of various cancers as an in vitro diagnostic kit for the diagnosis of beta glucuronidase-rich cancers.

Development and in vitro/in vivo evaluation of immediate release perindopril tablets.

Perindopril erbumine (PE) is a BCS (Biopharmaceutics Classification System) class 3 drug with high solubility and low permeability. It is an inhibitor of the enzyme that converts angiotensin I (Angiotensin Converting Enzyme, ACE) into angiotensin II as well as causing the degradation of the vasodilator bradykinin into an inactive heptapeptide. The aim of this study was to develop an alternative drug product by using a different salt of perindopril and to evaluate the bioequivalence between PE, not still licensed, and perindopril arginine (PA), licensed in many countries, and to prepare PE tablets by using direct compression method. Many different formulations were prepared, among which F3-coded formulation was only selected due to releasing of 98.03% active substance at 45th minute. Bioequivalence study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study and conducted in 24 male healthy volunteers via peroral route. The results of bioequivalence study were evaluated for Perindopril and Perindoprilat according to Cmax, tmax and AUC criteria. The geometric mean ratios (90% CI) of perindopril and perindoprilat followed test and reference drug were calculated for AUC0-t and Cmax, 105.946% (100.218-112.002%) and 110.437% (102.534-118.948%); 109.542% (98.364-121.992%) and 115.729% (101.031-132.565%), respectively. The 90% confidence intervals of them were found within the standard bioequivalence range (80-125%).

Does desloratadine alter the serum levels of montelukast when administered in a fixed-dose combination?

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the serum levels of montelukast when administered alone or in combination with desloratadine. STUDY DESIGN: A prospective crossover study. METHODS: Twenty-three healthy volunteers were investigated in two sessions. Volunteers were given 10 mg of montelukast orally with 250 mL water in the first session. The same subjects were given 10 mg of montelukast in fixed combination with 5 mg desloratadine 10 days after first session. Blood samples were collected 2, 3, and 4 hours after drug administration, and kept at -80°C after both applications. Plasma samples were analyzed for montelukast concentration. RESULTS: Mean concentration values of both groups were not statistically different (P > .05), but the differences were statistically significant according to time (P < .05). Statistically significant difference was not found between the groups according to the area under curve on the basis of both marginal and cumulative values for all different time intervals (P > .05). CONCLUSIONS: The absorption rate of montelukast was not altered when administered with desloratadine. This study suggested that desloratadine does not influence the bioavailability of montelukast, and their combination therapy can be used safely.

Effect of grapefruit juice on bioavailability of montelukast.

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate possible interactions between grapefruit juice and montelukast for up to 4 hours. STUDY DESIGN: A prospective, crossover study with 23 healthy volunteers was performed in two sessions. METHODS: In the first session, volunteers were treated with oral montelukast 10 mg once daily with 250 ml water. After a 10-day washout period, the same volunteers were treated with 10 mg montelukast with 250 ml grapefruit juice. Blood samples were collected 2, 3, and 4 hours after drug administration and kept at -80°C after both applications. Plasma samples were analyzed for montelukast concentration. RESULTS: The mean plasma concentration of montelukast across all time intervals was significantly greater (P = 0.0001) for those given grapefruit juice (517, 484, and 440) versus those treated with water (366, 356, and 292). Moreover, with respect to the time the sample was collected, there was no significant difference (P = 0.13) in the mean total plasma concentration up to 4 hours after montelukast ingestion for either group. There was a significant difference between the groups according to the area under curve with regard to marginal and cumulative values for all different time intervals (P < 0.05). CONCLUSIONS: Plasma concentration of montelukast was higher when administered with grapefruit juice, as compared to with water. This may have been due to the effect of grapefruit on liver metabolism of montelukast and the cytochrome P450 system.

Antioxidant, anti-inflammatory activities and acute toxicity of the polyherbal formulation: Romix®.

CONTEXT: Polyherbal formulations containing different plants are used for the treatment of various diseases. Romix® powder is a polyherbal formulation consisting of 14 traditionally used herbs and is used as a food supplement. There is no information about pharmaceutical activities of Romix®. OBJECTIVE: This study determined the total phenolic and total flavonoid content, and investigated the antioxidant and anti-inflammatory activities and acute toxicity of Romix®. MATERIAL AND METHODS: The total phenolics in the extracts were determined colorimetrically by using the Folin-Ciocalteu reagent. The total flavonoid content of the extracts was evaluated by a spectrophotometric method. The quercetin content of the extract was analyzed using the high-performance liquid chromatography (HPLC) method. Antioxidant activity of the extracts was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assays. The anti-inflammatory activity was evaluated by the carrageenan-induced paw edema test in the rat. RESULTS: The flavonoid and phenolics contents of Romix® were 50.58 and 265.83 mg/g in ethanol extract and 18.60 and 222.50 mg/g in water extract, respectively. Total quercetin content of Romix® was determined as 2.857 mg/g. Antioxidant activity results showed that ethanol extract in 1 mg/mL concentration (4.49775 µg/mL) had moderate antioxidant activity than water extract in the same concentration (4.28191 µg/mL). Intraperitoneal administration of 25 mg/kg Romix® extract exhibited anti-inflammatory activity and inhibited paw swelling at 1, 2, 3, 4, 5 and 6 h in rats with no acute toxicity. CONCLUSION: These findings suggest that Romix® due to its antioxidant and anti-inflammatory activities may be useful in the prevention or treatment of aging-related and inflammatory diseases.

Hypericum triquetrifolium Turra. Extract exhibits antiinflammatory activity in the rat.

The aim of the present study was to explore the probable antiinflammatory effect of Hypericum triquetrifolium Turra. in a rat model of carrageenan induced inflammation. Male Wistar rats were treated intraperitoneally with 0.4% dimethylsulphoxide (DMSO) (as control group) and H. triquetrifolium extract (25, 50, 60 mg/kg), 30 min before 0.1 ml 1% carrageenan injection. Paw volume was measured before and 1, 2, 3, 4, 5 and 6 h after the injection of carrageenan. The results are expressed as the mean+/-s.e. mean and the statistical significance of differences between groups was analyzed by One Way Analysis of Variance (ANOVA). The intraplantar injection of carrageenan caused a time-dependent paw edema in the rat although saline injection caused no swelling. Intraperitoneal administration of H. triquetrifolium extract (25, 50, 60 mg/kg) inhibited paw swelling dose-dependently at 2, 3, 4, 5 and 6 h after carrageenan injection (P<0.05). We can conclude that H. triquetrifolium extract may exert an antiinflammatory effect in rats.