Pharmacokinetics of 5-fluorouracil in the hamster following inhalation delivery of lipid-coated nanoparticles

Cory J. Hitzman, Lee W. Wattenberg, Timothy S. Wiedmann

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

The inhalation delivery of 5-fluorouracil (5-FU) in lipid-coated nanoparticles (LNPs) to hamsters was evaluated to determine the feasibility for use in lung cancer chemotherapy. The inhaled dose, 30 mg LNPs/kg body weight (1.5 mg/kg 5-FU), was delivered over an 8-min interval. Fluorescein isothiocyanate dextran (FITC-dextran) was included within the LNPs to provide an estimate of the particle concentration. The concentration of FITC-dextran and total 5-FU (released and LNP-associated) was determined as a function of time in the lung, trachea, larynx, esophagus, and serum. Concentrations of 5-FU and FITC-dextran were initially high in the trachea, larynx, and esophagus, and lower in the lung. Within 24 h, greater than 99% of the LNPs were cleared from the respiratory tract and total 5-FU concentrations mirrored the LNP concentration. An eight-compartment pharmacokinetic model was used to describe the observed trends in concentrations of LNPs and total 5-FU and to estimate the released 5-FU concentration in the above tissues. From this analysis, effective local targeting as well as sustained efficacious concentrations of 5-FU in the expected tumor sites were demonstrated.

Original languageEnglish (US)
Pages (from-to)1196-1211
Number of pages16
JournalJournal of Pharmaceutical Sciences
Volume95
Issue number6
DOIs
StatePublished - Jun 2006

Keywords

  • 5-fluorouracil
  • Aerosol distribution
  • Aerosol inhalation
  • Lipid-coated nanoparticles
  • Lung cancer
  • Mucociliary clearance
  • Pharmacokinetics
  • Sustained release

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