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Research ArticleArticle

Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

Rajendra S. Kadam, David W. A. Bourne and Uday B. Kompella
Drug Metabolism and Disposition July 2012, 40 (7) 1380-1388; DOI: https://doi.org/10.1124/dmd.112.044925
Rajendra S. Kadam
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David W. A. Bourne
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Uday B. Kompella
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Abstract

The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance.

Footnotes

  • This work was supported by the National Institutes of Health National Eye Institute [Grants R01-EY017533, R01-EY018940, R0-1EY017045].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    http://dx.doi.org/10.1124/dmd.112.044925.

  • ABBREVIATIONS:

    AUC
    area under the plasma concentration versus time curve
    GI
    gastrointestinal
    PK
    pharmacokinetic
    AIC
    Akaike information criterion.

  • Received February 8, 2012.
  • Accepted April 12, 2012.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 40 (7)
Drug Metabolism and Disposition
Vol. 40, Issue 7
1 Jul 2012
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Research ArticleArticle

PHARMACOKINETICS OF BIODEGRADABLE NANOPARTICLES

Rajendra S. Kadam, David W. A. Bourne and Uday B. Kompella
Drug Metabolism and Disposition July 1, 2012, 40 (7) 1380-1388; DOI: https://doi.org/10.1124/dmd.112.044925

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Research ArticleArticle

PHARMACOKINETICS OF BIODEGRADABLE NANOPARTICLES

Rajendra S. Kadam, David W. A. Bourne and Uday B. Kompella
Drug Metabolism and Disposition July 1, 2012, 40 (7) 1380-1388; DOI: https://doi.org/10.1124/dmd.112.044925
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