Abstract Title:

Pulmonary Administration of Water-soluble Curcumin Complex Reduces ALI Severity.

Abstract Source:

Am J Respir Cell Mol Biol. 2012 Feb 3. Epub 2012 Feb 3. PMID: 22312018

Abstract Author(s):

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

Article Affiliation:

Department of Surgery, University of Michigan, Ann Arbor, Michigan, United States.

Abstract:

Local or systemic inflammation can result in acute lung injury (ALI) and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, 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 facilitates direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin association with and transport across Calu-3 human airway epithelial cell monolayers compared to uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, while it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity ofALI in a murine model. Fluorescence microscopic examination revealed association of curcumin with cells throughout the lung. Administration of CDC following LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage (BAL) fluid and lung. CDC also reduced oxidant stress in the lungs and activation of the pro-inflammatory 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.

Study Type : Animal Study

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