Evaluation of the Physicochemical Properties, Pharmacokinetics, and In Vitro Anticancer Effects of Docetaxel and Osthol Encapsulated in Methoxy Poly(ethylene glycol)--Poly(caprolactone) Polymeric Micelles.

Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. To overcome these problems, we encapsulated DTX and OTH in methoxy poly(ethylene glycol)--poly(caprolactone) (mPEG--PCL) and conducted studies in vitro and in vivo.

Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Soluplus Polymeric Micelles Encapsulating Fenbendazole.

Fenbendazole (FEN), a broad-spectrum benzimidazole anthelmintic, suppresses cancer cell growth through various mechanisms but has low solubility and achieves low blood concentrations, which leads to low bioavailability. Solubilizing agents are required to prepare poorly soluble drugs for injections; however, these are toxic. To overcome this problem, we designed and fabricated low-toxicity Soluplus polymeric micelles encapsulating FEN and conducted toxicity assays in vitro and in vivo.

Revolutionizing technologies of nanomicelles for combinatorial anticancer drug delivery.

Insufficient efficacy of current single drug therapy of cancers have led to the advancement of combination drug-loaded formulations. Specifically, polymeric micelles have been focused on as efficient injectable vehicles for the delivery of several anticancer drugs simultaneously to cancer cells. These nano delivery systems have evolved with advancements in the area of nanotechnology.

Physicochemical, Pharmacokinetic, and Toxicity Evaluation of Methoxy Poly(ethylene glycol)--Poly(d,l-Lactide) Polymeric Micelles Encapsulating Alpinumisoflavone Extracted from Unripe Fruit.

Alpinumisoflavone, a major compound in unripe fruit is reported to exhibit numerous beneficial pharmacological activities, such as osteoprotective, antibacterial, estrogenic, anti-metastatic, atheroprotective, antioxidant, and anticancer effects. Despite its medicinal value, alpinumisoflavone is poorly soluble in water, which makes it difficult to formulate and administer intravenously (i.v.

Hepatic uptake of epirubicin by isolated rat hepatocytes and its biliary excretion after intravenous infusion in rats.

Anthracycline anticancer agents are widely used in the cancer chemotherapy for hepatocelluar carcinoma. However, accurate kinetic analyses of the hepatocellular uptake and efflux of the drugs have not been reported. We, therefore, investigated the hepatobiliary transport of epirubicin, an anthracycline derived antibiotic, after intravenous (i.

Extensive intracellular accumulation of ID-6105, a novel anthracycline, in SK-OV-3 ovarian cancer cells.

We investigated the anticancer activity of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, on weakly doxorubicin (Dox)-resistant SK-OV-3 ovarian cancer cells, and elucidated the relationship between its anticancer activity and accumulation in cells compared with those of Dox. Accumulation of ID-6105 in the cells was time-and concentration-dependent, a result of drug-induced cytotoxicity in the cells. SK-OV-3 cells were preloaded with ID-6105 or Dox for 12 h at concentrations ranging from 100 to 2000 nM and then incubated with drug-free medium for 0-48 h.

Pharmacokinetics of guanosine in rats following intravenous or intramuscular administration of a 1:1 mixture of guanosine and acriflavine, a potential antitumor agent.

A 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is under evaluation in preclinical studies as a possible antitumor agent. Guanosine is known to potentiate the anti-cancer activity of ACF. We therefore investigated the pharmacokinetics of guanosine following administration of the ACF/guanosine mixture in rats.

Determination of eperisone in human plasma by liquid chromatography-ESI-tandem mass spectrometry.

A sensitive and selective method for the determination of 4'-ethyl-3-methyl-3-piperidinopropiophenone hydrochloride (eperisone hydrochloride) in human plasma was developed and validated. The procedure employed an internal standard and a solvent extraction step followed by chromatography on a Xterra C18 minibore column. Detection was by electrospray ionization tandem mass spectrometry with multiple reaction monitoring.

Cytotoxic germacranolide sesquiterpene lactones from Carpesium triste var. manshuricum.

Four known germacranolide sesquiterpene lactones, 2alpha,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-isobutyloxy-germacran-8alpha,12-olide (1), 2alpha,5-epoxy-5,10-dihydroxy-6alpha,9beta-diangeloyloxy-germacran-8alpha,12-olide (2, divaricin B), 2alpha,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-(2-methylbutyloxy)-germacran-8alpha,12-olide (3) and 2alpha,5-epoxy-5,10-dihydroxy-6alpha-angeloyloxy-9beta-(3-methylbutyloxy)-germacran-8alpha,12-olide (4), were isolated from the chloroform-soluble fraction of the whole plants of Carpesium triste var. manshuricum. Their chemical structures were determined using spectroscopic methods, including 2D-NMR.

Effects of guanosine on the pharmacokinetics of acriflavine in rats following the administration of a 1:1 mixture of acriflavine and guanosine, a potential antitumor agent.

Preclinical studies are currently underway to examine the potential antitumor effects of a 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine. Guanosine potentiates the anticancer activity of some compounds. However, the effects of guanosine on the pharmacokinetics of ACF in mammals are unknown.

Endogenous sphingolipid metabolites related to the growth in Sphingomonas chungbukensis.

Sphingolipids are present in animals, plants, fungi, yeasts and some bacteria. In mammalian cells sphingolipids act as lipid mediators for cell growth, differentiation, apoptosis and angiogenesis. In contrast, in bacteria the biological significance of sphingolipids has not been fully elucidated and sphingolipid metabolism has not been investigated.

Physicochemical characteristics and bioavailability of a novel intestinal metabolite of ginseng saponin (IH901) complexed with beta-cyclodextrin.

In an effort to improve the bioavailability (BA) of the insoluble compound 20-O-(beta-d-glucopyranosyl)-20(S)-protopanaxadiol (IH901), we prepared beta-cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) inclusion complexes containing IH901. IH901 is a major metabolite formed by intestinal bacteria from protopanaxadiol ginseng saponins. We developed and validated an HPLC-based method to measure IH901 levels from samples prepared in vitro.

PCR-based detection of Mycoplasma species.

In this study, we describe our newly-developed sensitive two-stage PCR procedure for the detection of 13 common mycoplasmal contaminants (M. arthritidis, M. bovis, M.

Pharmacokinetic characteristics and hepatic distribution of IH-901, a novel intestinal metabolite of ginseng saponin, in rats.

We investigated the pharmacokinetic characteristics of 20- O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), a metabolite that is formed by intestinal bacteria, after its intravenous (i.v.) or oral administration in rats.

Determination of mequitazine in human plasma by gas-chromatography/mass spectrometry with ion-trap detector and its pharmacokinetics after oral administration to volunteers.

The objective of this study was to develop an assay for mequitazine (MQZ) for the study of the bioavailability of the drug in human subjects. Using one mL of human plasma, the pH of the sample was adjusted and MQZ in the aqueous phase extracted with hexane; the organic layer was then evaporated to dryness, reconstituted and an aliquot introduced to a gas chromatograph/mass spectrometer (GC/MS) system with ion-trap detector. Inter- and intra-day precision of the assay were less than 15.

High performance liquid chromatographic analysis an pharmacokinetic characteristics of ID-7181, a novel quaternary ammoniopropenyl cephalosporin, following intravenous and intramuscular injections to rats.

The purpose of the present study was to examine the pharmacokinetic characteristics of 7-[(z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[(E)-3-(E)-(1-carbamoyl-1-propene-3-yl) 3-ethylmethylammonio]-1-propene- 1-yl]-3-cepheme-4-carboxylate (CAS 206126-08-1, ID-7181), a novel quaternary ammoniopropenyl cephalosporin that contains two vinyl groups at the C-3 side chain, after being administered intravenously (i.v.) or intramuscularly (i.

Induction of apoptotic cell death by 2'-hydroxycinnamaldehyde is involved with ERK-dependent inactivation of NF-kappaB in TNF-alpha-treated SW620 colon cancer cells.

2'-Hydroxycinnamaldehyde (HCA) inhibits cell growth of several human cancer cells with unknown mechanisms. We investigated the inhibitory effect of HCA on TNF-alpha-induced cell growth and possible signal pathway in SW620 colon cancer cells. HCA inhibited TNF-alpha-induced SW620 colon cell growth in time- and dose-dependent manner through induction of apoptotic cell death.

A set of epitope-tagging integration vectors for functional analysis in Saccharomyces cerevisiae.

Functional analysis of genes from Saccharomyces cerevisiae has been the major goal after determination of genome sequences. Even though several tools for molecular-genetic analyses have been developed, only a limited number of reliable genetic tools are available to support functional assay at protein level. Epitope tagging is a powerful tool for detecting, purifying, and functional studying of proteins.

Pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after i.v. bolus multiple administration in rats.

We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats.

HPLC analysis and pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, in rats and beagle dogs.

We investigated the pharmacokinetic characteristics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration in rats and beagle dogs.

HPLC determination and pharmacokinetics of endogenous acetyl-L-carnitine (ALC) in human volunteers orally administered a single dose of ALC.

Acetyl-L-carnitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, validation of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacokinetics after oral administration of ALC to human volunteers.

Pharmacokinetics of PEG-hemoglobin SB1, a hemoglobin-based oxygen carrier, after its intravenous administration in beagle dogs.

The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity (r2=0.

Pharmacokinetics and bioequivalence of tiropramide in healthy volunteers.

Two formulations of tiropramide ((+/-)alpha-(benzoylamino)-4-[2-(diethylamino) ethoxy]-N,N-dipropyl-benzenepropanamide hydrochloride, CAS 55837-29-1), an antispasmodic agent, were orally administered to 16 healthy volunteers by the Latin cross-over design with the purpose of evaluating bioequivalence and pharmacokinetics of tiropramide. Tiropramide in human plasma was determined by a gas chromatography/nitrogen phosphorus detector. The detection limit of tiropramide was 5 ng/ml.

Quantitative analysis of tiropramide in human blood by gas chromatography with nitrogen-phosphorus detector.

The analytical method of antispasmodic agent tiropramide ((+/-)alpha-(benzoylamino)-4-[2-(diethylamino)ethoxy]-N,N-dipropylbenzenepropanamide hydrochloride) was developed by gas chromatography/nitrogen-phosphorus detector (GC/NPD) in human plasma. Two kinds of tiropramide tablets were orally administered to volunteers by Latin square crossover design, and blood was withdrawn as designed schedule. The plasma of 1 mL was loaded on Sep-pak C18 cartridge and eluted with methanol after washing with 30% methanol.