Characterization and pharmacokinetic analysis of tacrolimus dispersion for nebulization in a lung transplanted rodent model

Alan B. Watts, Adam M. Cline, Adham R. Saad, Scott B. Johnson, Jay I. Peters, Robert O. Williams

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Lung transplantation animal models have been well established and enabled the investigation of a variety of new pharmacotherapeutic strategies for prevention of lung allograft rejection. Direct administration of immunosuppressive agents to the lung is a commonly investigated approach; however, can prove challenging due to the poor solubility of the drug molecule, the tortuous pathways of the lung periphery, and the limited number of excipients approved for inhalation. In this study, we aimed to evaluate a solubility enhancing formulation of tacrolimus for localized therapy in a lung transplanted rat model and determine the extent of drug absorption into systemic circulation. Characterization of the nebulized tacrolimus dispersion for nebulization showed a fine particle fraction (FPF) of 46.1% and a mass median aerodynamic diameter (MMAD) of 4.06 μm. After single dose administration to transplanted and non-transplanted rats, a mean peak transplanted lung concentration of 399.8 ± 29.2 ng/g and mean peak blood concentration of 4.88 ± 1.6 ng/mL were achieved. It is theorized that enhanced lung retention of tacrolimus is due to lipophilic associations with bronchial tissue and phospholipid surfactants in lung fluid. These findings indicate that tacrolimus dispersion for nebulization can achieve highly localized therapy for lung transplant recipients.

Original languageEnglish (US)
Pages (from-to)46-52
Number of pages7
JournalInternational Journal of Pharmaceutics
Volume384
Issue number1-2
DOIs
StatePublished - Jan 15 2010

Keywords

  • Lung transplant
  • Nanoparticles
  • Preclinical
  • Pulmonary delivery
  • Tacrolimus

ASJC Scopus subject areas

  • Pharmaceutical Science

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