Polymeric curcumin nanoparticle pharmacokinetics and metabolism in bile duct cannulated rats

Peng Zou, Lawrence Helson, Anirban Maitra, Stephan T. Stern, Scott E. McNeil

Research output: Contribution to journalArticle

Abstract

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle-encapsulated (nanocurcumin) and solvent-solubilized curcumin formulations in Sprague-Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon intravenous (i.v.) administration of nanocurcumin only nanoparticle-encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent-solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent-solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested a rapid "burst" release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent-solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent-solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations.

Original languageEnglish (US)
Pages (from-to)1977-1987
Number of pages11
JournalMolecular Pharmaceutics
Volume10
Issue number5
DOIs
StatePublished - May 6 2013

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Curcumin
Bile Ducts
Nanoparticles
Pharmacokinetics
Sprague Dawley Rats
Neoplasms
Jugular Veins
Bile
Intravenous Administration

Keywords

  • biliary excretion
  • curcumin
  • metabolite profile
  • nanoformulation
  • urinary excretion

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

Cite this

Polymeric curcumin nanoparticle pharmacokinetics and metabolism in bile duct cannulated rats. / Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

In: Molecular Pharmaceutics, Vol. 10, No. 5, 06.05.2013, p. 1977-1987.

Research output: Contribution to journalArticle

Zou, Peng ; Helson, Lawrence ; Maitra, Anirban ; Stern, Stephan T. ; McNeil, Scott E. / Polymeric curcumin nanoparticle pharmacokinetics and metabolism in bile duct cannulated rats. In: Molecular Pharmaceutics. 2013 ; Vol. 10, No. 5. pp. 1977-1987.
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