ArticleJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2016
Anticancer 20(R)-dammarane-3β,12β,20,25-tetrol-loaded polymeric micelles: Preparation, quantification and pharmacokinetics.
Article in Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors at 4 institutions in 2 countries.
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Abstract
Polymeric micelles are effective drug-loading sites and often used to formulate poorly water-soluble agents. In the present study, the amphiphilic copolymer methoxy-capped poly(ethyleneglycol)-block-poly(Ɛ-caprolactone) (mPEG-b-PCL) was successfully developed for the delivery of 20(R)-dammarane-3β,12β,20,25-tetrol (25-OH-PPD), a natural anticancer product from Panax notoginseng. The 25-OH-PPD-loaded micelles were characterized by morphological observation and thermodynamic stability testing. The concentrations of 25-OH-PPD was determined by HPLC-MS/MS. The optimum MRM transition of 25-OH-PPD was selected at m/z 479.4.0→461.4. The chromatographic separation was achieved on a SB-C18 column (1.8μm, 2.1×50mm) with an optimized gradient mobile phase system. The extraction recoveries of plasma and various tissue homogenates were within the range of 81.1%-110.4% and the matrix effects ranged from 81.9% to 106.7%. The intra- and inter- day precision values (RSD%) were less than 12.0%, with accuracies ranging from 85.2% to 114.2%. In addition, 25-OH-PPD was found to be stable in different biological matrix after three freeze-thaw cycles, at room temperature and at -70°C for 4 weeks. The pharmacokinetics of 25-OH-PPD-loaded micelles was evaluated in rats. The micelles appeared as transparent liquid, stable and uniform spheres with an average particle size of 35.4±4.2nm. The maximum concentration of 25-OH-PPD in micelles was much lower than in free drug preparation. However, the drug in the micelles was released steadily, with a t1/2 of 9.1±4.0h, significantly longer than in free drug (3.3±1.4h). However, the drug concentrations in tissues after the micelle administration were lower than the levels after administration of the free drugs. In summary, the micelles were characterized by long circulation and sustained release, with an ability to avoid uptake by the reticuloendothelial system, providing a promising approach to deliver intravenous 25-OH-PPD for therapy.
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