Comparative pharmacokinetics of a marker compound, baicalin in KOB extract after oral administration to normal and allergic-induced rats.

KOB extracts are a polyherbal medicine had been prescribed for the treatment of hyperhydrosis and allergic diseases such as allergic asthma and rhinitis in oriental clinics. Therefore, the pharmacokinetic studies of the KOB extract administered orally to normal rats and rhinitis-induced rats to understand the correlation of the efficacy and plasma concentration of KOB in patients of allergic rhinitis in future were performed. The study was conducted according to administration for pure baicalin in normal rats, baicalin in KOB extract in normal rats and rhinitis-induced rats. Baicalin in rat plasma was analyzed and validated by HPLC analysis. The interday precision based on the standard deviation of replicates of quality control samples ranged from 3.6% to 7.9% with accuracy ranging from 92.9% to 101.2% for baicalin. Based on validated analysis, pharmacokinetic study was carried out. Pure baicalin in normal rats and baicalin in KOB extract in normal rats showed bimodal curves due to direct absorption and glucuronidation. The Tmax, Cmax and AUC of pure baicalin in normal rats or baicalin in KOB extract in normal rats were 12 h, 0.68 µg/ml and 9.85 µg h/ml, respectively, or 12 h, 0.46 µg/ml and 6.36 µg h/ml, respectively. The analytical method showed excellent sensitivity, precision and accuracy, being successfully employed in a pharmacokinetic study of polyherbal medicine, KOB extract. Allergic-induced condition did not affect the pharmacokinetics of KOB extracts, suggesting KOB extracts did not require dosage adjustment in subjects with allergic-induced diseases.

Surface-modified gemcitabine with mucoadhesive polymer for oral delivery.

Gemcitabine microparticles were prepared using chitosan, polyethylene oxide or carbopol as the mucoadhesive polymer and eudragit L100-55 as the enteric polymer by a double emulsion method. The particle size and zeta potential changed from 1338.3 ± 254.1 nm to 2459.4 ± 103.6 nm and -5.16 ± 1.62 mV to 2.84 ± 0.65 mV, respectively, with increasing chitosan to gemcitabine weight ratio from 0.25 to 1. The gemcitabine-loaded microparticles without mucoadhesive polymer (F50) showed the particle size and zeta potential of 671.3 ± 58.3 nm and - 16.7 ± 1.82 mV, respectively. The cellular uptake of gemcitabine into Caco-2 cells from gemcitabine-loaded microparticles with chitosan increased with increasing incubation time in Caco-2 cells compared to that of gemcitabine-loaded microparticles with polyethylene oxide or carbopol, suggesting that chitosan might be the optimal mucoadhesive polymer. Gemcitabine microparticles will be tested to identify whether the oral absorption could be increased in the future.

Preparation and evaluation of polymeric microparticulates for improving cellular uptake of gemcitabine.

BACKGROUND: Gemcitabine must be administered at high doses to elicit the required therapeutic response because of its very short plasma half-life due to rapid metabolism. These high doses can have severe adverse effects. METHODS: In this study, polymeric microparticulate systems of gemcitabine were prepared using chitosan as a mucoadhesive polymer and Eudragit L100-55 as an enteric copolymer. The physicochemical and biopharmaceutical properties of the resulting systems were then evaluated. RESULTS: There was no endothermic peak for gemcitabine in any of the polymeric gemcitabine microparticulate systems, suggesting that gemcitabine was bound to chitosan and Eudragit L100-55 and its crystallinity was changed into an amorphous form. The polymeric gemcitabine microparticulate system showed more than 80% release of gemcitabine in 30 minutes in simulated intestinal fluid. When mucin particles were incubated with gemcitabine polymeric microparticulates, the zeta potential of the mucin particles was increased to 1.57 mV, indicating that the polymeric gemcitabine microparticulates were attached to the mucin particles. Furthermore, the F53 polymeric gemcitabine microparticulates having 150 mg of chitosan showed a 3.8-fold increased uptake of gemcitabine into Caco-2 cells over 72 hours compared with gemcitabine solution alone. CONCLUSION: Overall, these results suggest that polymeric gemcitabine microparticulate systems could be used as carriers to help oral absorption of gemcitabine.

Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid.

BACKGROUND: Nanoparticles fabricated from the biodegradable and biocompatible polymer, polylactic-co-glycolic acid (PLGA), are the most intensively investigated polymers for drug delivery systems. The objective of this study was to explore fully the development of a PLGA nanoparticle drug delivery system for alternative preparation of a commercial formulation. In our nanoparticle fabrication, our purpose was to compare various preparation parameters. METHODS: Docetaxel-loaded PLGA nanoparticles were prepared by a single emulsion technique and solvent evaporation. The nanoparticles were characterized by various techniques, including scanning electron microscopy for surface morphology, dynamic light scattering for size and zeta potential, x-ray photoelectron spectroscopy for surface chemistry, and high-performance liquid chromatography for in vitro drug release kinetics. To obtain a smaller particle, 0.2% polyvinyl alcohol, 0.03% D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), 2% Poloxamer 188, a five-minute sonication time, 130 W sonication power, evaporation with magnetic stirring, and centrifugation at 8000 rpm were selected. To increase encapsulation efficiency in the nanoparticles, certain factors were varied, ie, 2-5 minutes of sonication time, 70-130 W sonication power, and 5-25 mg drug loading. RESULTS: A five-minute sonication time, 130 W sonication power, and a 10 mg drug loading amount were selected. Under these conditions, the nanoparticles reached over 90% encapsulation efficiency. Release kinetics showed that 20.83%, 40.07%, and 51.5% of the docetaxel was released in 28 days from nanoparticles containing Poloxamer 188, TPGS, or polyvinyl alcohol, respectively. TPGS and Poloxamer 188 had slower release kinetics than polyvinyl alcohol. It was predicted that there was residual drug remaining on the surface from x-ray photoelectron spectroscopy. CONCLUSION: Our research shows that the choice of surfactant is important for controlled release of docetaxel.