Pharmacodynamic Analysis of Magnetic Resonance Imaging-Monitored Focused Ultrasound-Induced Blood-Brain Barrier Opening for Drug Delivery to Brain Tumors.

Pharmacodynamic analysis of magnetic resonance imaging-monitored focused ultrasound-induced blood-brain barrier opening for drug delivery to brain tumors.

Biomed Res Int. 2013; 2013: 627496
Chu PC, Chai WY, Hsieh HY, Wang JJ, Wey SP, Huang CY, Wei KC, Liu HL

Microbubble-enhanced focused ultrasound (FUS) can enhance the delivery of therapeutic agents into the brain for brain tumor treatment. The purpose of this study was to investigate the influence of brain tumor conditions on the distribution and dynamics of small molecule leakage into targeted regions of the brain after FUS-BBB opening. A total of 34 animals were used, and the process was monitored by 7T-MRI. Evans blue (EB) dye as well as Gd-DTPA served as small molecule substitutes for evaluation of drug behavior. EB was quantified spectrophotometrically. Spin-spin (R1) relaxometry and area under curve (AUC) were measured by MRI to quantify Gd-DTPA. We found that FUS-BBB opening provided a more significant increase in permeability with small tumors. In contrast, accumulation was much higher in large tumors, independent of FUS. The AUC values of Gd-DTPA were well correlated with EB delivery, suggesting that Gd-DTPA was a good indicator of total small-molecule accumulation in the target region. The peripheral regions of large tumors exhibited similar dynamics of small-molecule leakage after FUS-BBB opening as small tumors, suggesting that FUS-BBB opening may have the most significant permeability-enhancing effect on tumor peripheral. This study provides useful information toward designing an optimized FUS-BBB opening strategy to deliver small-molecule therapeutic agents into brain tumors. HubMed – drug


Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry for Identification of In Vitro and In Vivo Metabolites of Bornyl Gallate in Rats.

J Anal Methods Chem. 2013; 2013: 473649
Lan W, Bian L, Zhao X, Jia P, Meng X, Wu Y, Wang S, Liao S, Yu J, Zheng X

Bornyl gallate (BG) is a potential drug candidate synthesized by the reaction of two natural products, gallic acid and borneol. Previous studies have strongly suggested that BG is worthy of further investigation due to antioxidant, antiatherosclerosis activities, and obvious activity of stimulating intersegmental vessel growth in zebrafish. This work was designed to elucidate the metabolic profile of BG through analyzing its metabolites in vitro and in vivo by a chromatographic separation coupled with a mass spectrometry. The metabolites of BG were characterized from the rat liver microsome incubation solution, as well as rat urine and plasma after oral administration. Chromatographic separation was performed on an Agilent TC-C18 column (250?mm?×?4.6?mm, 5? ? m) with gradient elution using methanol and water containing 0.2% (V?:?V) formic acid as the mobile phase. Metabolites identification involved analyzing the retention behaviors, changes of molecular weights and MS/MS fragment patterns of BG and the metabolites. Five compounds were identified as isomers of hydroxylated BG metabolites in vitro. The major metabolites of BG in rat urine and plasma proved to be BG-O-glucuronide and O-methyl BG-O-glucuronide. The proposed method confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of BG. HubMed – drug


Rapid screening of drug-protein binding using high-performance affinity chromatography with columns containing immobilized human serum albumin.

J Anal Methods Chem. 2013; 2013: 439039
Li YF, Zhang XQ, Hu WY, Li Z, Liu PX, Zhang ZQ

For drug candidates, a plasma protein binding (PPB) more than 90% is more meaningful and deserves further investigation in development. In the study, a high-performance liquid chromatography method employing column containing immobilized human serum albumin (HSA) to screen in vitro PPB of leading compounds was established and successfully applied to tested compounds. Good correlation (a coefficient correlation of 0.96) was attained between the reciprocal values (X) of experimentally obtained retention time of reference compounds eluted through HSA column and the reported PPB values (Y) with a correlation equation of Y = 92.03 – 97.01X. The method was successfully applied to six test compounds, and the result was confirmed by the conventional ultrafiltration technique, and both yielded equal results. However, due to the particular protein immobilized to column, the method cannot be applied for all compounds and should be exploited judiciously based on the value of the logarithmic measure of the acid dissociation constant (pKa) as per the requirement. If ?1-acid glycoprotein and other plasma proteins could be immobilized like HSA with their actual ratio in plasma to column simultaneously, the result attained using immobilized column may be more accurate, and the method could be applied to more compounds without pKa limitation. HubMed – drug


Headspace single-drop microextraction gas chromatography mass spectrometry for the analysis of volatile compounds from herba asari.

J Anal Methods Chem. 2013; 2013: 380705
Wang GJ, Tian L, Fan YM, Qi ML

A rapid headspace single-drop microextraction gas chromatography mass spectrometry (SDME-GC-MS) for the analysis of the volatile compounds in Herba Asari was developed in this study. The extraction solvent, extraction temperature and time, sample amount, and particle size were optimized. A mixed solvent of n-tridecane and butyl acetate (1?:?1) was finally used for the extraction with sample amount of 0.750?g and 100-mesh particle size at 70°C for 15?min. Under the determined conditions, the pound samples of Herba Asari were directly applied for the analysis. The result showed that SDME-GC-MS method was a simple, effective, and inexpensive way to measure the volatile compounds in Herba Asari and could be used for the analysis of volatile compounds in Chinese medicine. HubMed – drug


Protective effect of quercetin on chloroquine-induced oxidative stress and hepatotoxicity in mice.

Malar Res Treat. 2013; 2013: 141734
Kumar Mishra S, Singh P, Rath SK

The present study was aimed to find out the protective effect of quercetin on hepatotoxicity resulting by commonly used antimalarial drug chloroquine (CQ). Swiss albino mice were administered with different amounts of CQ ranging from human therapeutic equivalent of 360?mg/kg body wt. to as high as 2000?mg/kg body wt. We observed statistically significant generation of reactive oxygen species, liver toxicity, and oxidative stress. Our observation of alterations in biochemical parameters was strongly supported by real-time PCR measurement of mRNA expression of key biochemical enzymes involved in hepatic toxicity and oxidative stress. However, the observed hepatotoxicity and accompanying oxidative stress following CQ administration show dose specific pattern with little or apparently no effect at therapeutic dose while having severe effects at higher dosages. We further tested quercetin, an antioxidant flavanoid, against CQ-induced hepatoxicity and found encouraging results as quercetin was able to drastically reduce the oxidative stress and hepatotoxicity resulting at higher dosages of CQ administration. In conclusion, our study strongly suggests co administration of antioxidant flavonoid like quercetin along with CQ for antimalarial therapy. This is particularly important when CQ is administered as long-term prophylactic treatment for malaria as chronic exposure has shown to be resulting in higher dose level of drug in the body. HubMed – drug