Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice

David C. Bibby, James E Talmadge, Milind K. Dalal, Scott G. Kurz, Kevin M. Chytil, Stephen E. Barry, David G. Shand, Matthias Steiert

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

We report the biodistribution and pharmacokinetics (PK) of a cyclic RGD-doxorubicin-nanoparticle (NP) formulation in tumor-bearing mice. The NP core was composed of inulin multi-methacrylate with a targeting peptide, cyclic RGD, covalently attached to the NPs via PEG-400. Seventy-two percent of the doxorubicin was attached to the NP matrix via an amide bond; 28% of doxorubicin was entrapped as unconjugated drug. The PK of total, unconjugated and metabolized doxorubicin was examined for 5 days following intravenous (i.v.) administration of the NP formulation (250 μg doxorubicin equiv.), revealing a bi-exponential fix with a terminal half-life of 5.99 h. In addition, the biodistribution studies revealed decreasing drug concentrations over time in the heart, lung, kidney and plasma and accumulating drug concentrations in the liver, spleen and tumor. The drug concentration in these latter tissues peaked between 24 and 48 h with the liver, spleen and tumor containing 56, 3.5 and 1.8% of the administered dose at t = 48 h, respectively. In contrast to all of the organs studied, the tumors contained high levels of a doxorubicin metabolite.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume293
Issue number1-2
DOIs
StatePublished - Apr 11 2005

Fingerprint

Nanoparticles
Doxorubicin
Pharmacokinetics
Neoplasms
Pharmaceutical Preparations
Spleen
Inulin
Methacrylates
Liver
Amides
Intravenous Administration
Half-Life
Kidney
Lung
Peptides
cyclic arginine-glycine-aspartic acid peptide

Keywords

  • Biodistribution
  • Doxorubicin
  • Mice
  • Nanoparticles
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice. / Bibby, David C.; Talmadge, James E; Dalal, Milind K.; Kurz, Scott G.; Chytil, Kevin M.; Barry, Stephen E.; Shand, David G.; Steiert, Matthias.

In: International Journal of Pharmaceutics, Vol. 293, No. 1-2, 11.04.2005, p. 281-290.

Research output: Contribution to journalArticle

Bibby, David C. ; Talmadge, James E ; Dalal, Milind K. ; Kurz, Scott G. ; Chytil, Kevin M. ; Barry, Stephen E. ; Shand, David G. ; Steiert, Matthias. / Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice. In: International Journal of Pharmaceutics. 2005 ; Vol. 293, No. 1-2. pp. 281-290.
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