Pulmonary administration of a water-soluble curcumin complex reduces severity of acute lung injury.
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 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.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Emory University/Atlanta Veterans Affairs Medical Center, 1670 Clairmont Road, Atlanta, GA 30033, USA.
Madathilparambil V
MV
Suresh
Matthew C
MC
Wagner
Gus R
GR
Rosania
Kathleen A
KA
Stringer
Kyoung Ah
KA
Min
Linda
L
Risler
Danny D
DD
Shen
George E
GE
Georges
Aravind T
AT
Reddy
Jaakko
J
Parkkinen
Raju C
RC
Reddy
D055371:Acute Lung Injury / Q000517:prevention & control*; D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004333:Drug Administration Routes; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D012995:Solubility
D003474:Curcumin