A physiologically based pharmacokinetic
model was developed to
describe the tissue distribution kinetics of a dendritic nanoparticle
and its conjugated active pharmaceutical ingredient (API) in plasma,
liver, spleen, and tumors. Tumor growth data from MV-4-11 tumor-bearing
mice were incorporated to investigate the exposure/efficacy relationship.
The nanoparticle demonstrated improved antitumor activity compared
to the conventional API formulation, owing to the extended released
API concentrations at the site of action. Model simulations further
enabled the identification of critical parameters that influence API
exposure in tumors and downstream efficacy outcomes upon nanoparticle
administration. The model was utilized to explore a range of dosing
schedules and their effect on tumor growth kinetics, demonstrating
the improved antitumor activity of nanoparticles with less frequent
dosing compared to the same dose of naked APIs in conventional formulations.
A novel high-performance liquid chromatographic method with mass spectrometry and diode array detection method for the simultaneous qualitative and quantitative analysis of bioactive phenols was developed. In total, nine chemically diverse phenols including five bibenzyls, three phenanthrenes and a coumarin were unambiguously identified in Dendrobium aurantiacum var. denneanum by comparison with the available references or reported data according to their retention behaviors, UV spectra and fragmentations of ESI-MS. The contents of the four main phenolic compounds, moscatilin, gigantol, moscatin and coumarin, in D. aurantiacum var. denneanum from the wild and various cultivated populations were determined by HPLC-UV. The sample preparation involved a rapid and simple procedure based on solid-phase extraction using a C(18) reversed-phase cartridge. The quantitative analysis was performed on a Beckman Coulter ODS column (5 microm, 250 x 4.6 mm) using a linear gradient elution system of acetonitrile-0.5% formic acid. The method was validated for linearity, limits of detection (LOD) and quantification (LOQ), precision and accuracy. Good results were obtained with respect to the overall intra- and inter-day variations (RSD less than 3.22%) and the percentage recoveries (ranging from 90.50 to 99.22%). Notable differences in the contents of phenols were observed among different cultivated populations. The samples colleted in April and May (spring), or October and November (autumn) accumulated much higher contents of phenols than those collected in other seasons.
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