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Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS

Overview of attention for article published in International Journal of Nanomedicine, April 2012
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15 Mendeley
Title
Pharmacokinetics, tissue distribution, and metabolites of a polyvinylpyrrolidone-coated norcantharidin chitosan nanoparticle formulation in rats and mice, using LC-MS/MS
Published in
International Journal of Nanomedicine, April 2012
DOI 10.2147/ijn.s29696
Pubmed ID
Authors

Xue-Nong Zhang

Abstract

A novel formulation containing polyvinylpyrrolidone (PVP) K(30)-coated norcantharidin (NCTD) chitosan nanoparticles (PVP-NCTD-NPs) was prepared by ionic gelation between chitosan and sodium tripolyphosphate. The average particle size of the PVP-NCTD-NPs produced was 140.03 ± 6.23 nm; entrapment efficiency was 56.33% ± 1.41%; and drug-loading efficiency was 8.38% ± 0.56%. The surface morphology of NCTD nanoparticles (NPs) coated with PVP K(30) was characterized using various analytical techniques, including X-ray diffraction and atomic force microscopy. NCTD and its metabolites were analyzed using a sensitive and specific liquid chromatography-tandem mass spectrometry method with samples from mice and rats. The results indicated the importance of the PVP coating in controlling the shape and improving the entrapment efficiency of the NPs. Pharmacokinetic profiles of the NCTD group and PVP-NCTD-NP group, after oral and intravenous administration in rats, revealed that relative bioavailabilities were 173.3% and 325.5%, respectively. The elimination half-life increased, and there was an obvious decrease in clearance. The tissue distribution of NCTD in mice after the intravenous administration of both formulations was investigated. The drug was not quantifiable at 6 hours in all tissues except for the liver and kidneys. The distribution of the drug in the liver and bile was notably improved in the PVP-NCTD-NP group. The metabolites and excretion properties of NCTD were investigated by analyzing rat feces and urine samples, collected after oral administration. A prototype drug and two metabolites were found in the feces, and seven metabolites in the urine. The primary elimination route of NCTD was via the urine. The quantity of the parent drug eliminated in the feces of the PVP-NCTD-NP group, was 32 times greater than that of the NCTD group, indicating that the NPs dramatically increased the reduction quantity from liver to bile. We conclude that PVP-NCTD-NPs are an adequate formulation for enhancing the absorption of NCTD, and significantly improving therapeutic effects targeting the hepatic system. Decarboxylation and hydroxylation were the dominant metabolic pathways for NCTD. Metabolites were mainly excreted into rat kidney and finally into urine.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 15 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 7%
Unknown 14 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 33%
Student > Master 4 27%
Researcher 1 7%
Student > Postgraduate 1 7%
Student > Bachelor 1 7%
Other 0 0%
Unknown 3 20%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 20%
Chemistry 3 20%
Pharmacology, Toxicology and Pharmaceutical Science 2 13%
Physics and Astronomy 1 7%
Environmental Science 1 7%
Other 2 13%
Unknown 3 20%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 April 2012.
All research outputs
#9,957,201
of 12,438,331 outputs
Outputs from International Journal of Nanomedicine
#1,919
of 2,456 outputs
Outputs of similar age
#85,890
of 120,428 outputs
Outputs of similar age from International Journal of Nanomedicine
#43
of 78 outputs
Altmetric has tracked 12,438,331 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,456 research outputs from this source. They receive a mean Attention Score of 3.0. This one is in the 12th percentile – i.e., 12% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 120,428 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 78 others from the same source and published within six weeks on either side of this one. This one is in the 33rd percentile – i.e., 33% of its contemporaries scored the same or lower than it.