Polymeric Curcumin Nanoparticle Pharmacokinetics and
Metabolism in Bile Duct Cannulated Rats
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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 <i>in vivo</i> 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 (<i>n</i> = 5). Nanocurcumin
increased the plasma <i>C</i><sub>max</sub> 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