Pulmonary administration of a water-soluble curcumin complex reduces severity of acute lung injury

Madathilparambil V. Suresh, Matthew C. Wagner, Gus R. Rosania, Kathleen A. Stringer, Kyoung Ah Min, Linda Risler, Danny D. Shen, George E. Georges, Aravind T. Reddy, Jaakko Parkkinen, Raju C. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, andhypoxemia.Curcumin, a plant-derivedpolyphenoliccompound, exhibits potent anti-inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-γ- cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin's association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-κB. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung targeted, curcumin-based therapy for the treatment of patients with ALI.

Original languageEnglish (US)
Pages (from-to)280-287
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume47
Issue number3
DOIs
StatePublished - Sep 2012

Keywords

  • Calu-3
  • Cyclodextrin
  • LPS
  • Oxidative stress
  • TEER
  • Turmeric

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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