Pulmonary delivery of resveratrol-β-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury

Abstract

Smoke bombs are often used in military/fire training, which can produce a large amount of zinc chloride (ZnCl 2 ) smoke. Inhalation of ZnCl 2 smoke usually causes acute lung injury (ALI) that would likely develop to acute respiratory distress syndrome (ARDS). However, there is no effective prevention or treatment strategy for the smoke-induced ALI. Resveratrol (RES) is a natural polyphenol with good anti-inflammatory and anti-apoptotic activities, but its low solubility, stability, and bioavailability restrict its clinical application. In this study, an inhalable RES formulation composed of RES- β -cyclodextrin inclusion complexes (RES- β -CD) was prepared for the prevention of ZnCl 2 smoke-induced ALI. RES- β -CD powders had a small mass median aerodynamic diameter of 3.61 μm and a high fine particle fraction of 38.84%, suitable for pulmonary inhalation. RES- β -CD exhibited low BEAS-2B cytotoxicity. Pulmonary delivery of RES- β -CD to mice remarkably prevented the smoke-induced ALI with downregulation of TNF- α , IL-1 β , STAT3, and GATA3, and upregulation of T-bet and Foxp3. RES- β -CD protected the respiratory function, percutaneous oxygen saturation, physical activity, lung capillary integrity, and lung liquid balance, alleviating inflammation and apoptosis. Pulmonary delivery of the positive drug, budesonide (BUD), also alleviated the smoke-induced ALI by reduction of inflammation and cell apoptosis. RES- β -CD exhibited the regulation of the Th1/Th2 and Treg/Th17 balances, while BUD did not show any effect on immune balances. In conclusion, pulmonary delivery of RES- β -CD is a promising anti-inflammatory and anti-apoptosis strategy for the prevention of ZnCl 2 smoke-induced ALI by direct lung drug distribution and regulation of immune balance.

IL-33 Deficiency Attenuates Lung Inflammation by Inducing Th17 Response and Impacting the Th17/Treg Balance in LPS-Induced ARDS Mice via Dendritic Cells

“…Moreover, the relationship between Th17 cells and Treg cells is inseparable, and Th17 cells can influence the immunosuppressive effect of Treg cells [45]. The Th17/Treg balance is critical in maintaining immune homeostasis, and restoring the Th17/Treg balance can reduce inflammation in ALI [46]. Recent experimental evidence revealed that IL-33 plays a multifaceted role in the development and maintenance of the Th17 immune response.…”

Drugs against metabolic diseases as potential senotherapeutics for aging-related respiratory diseases

“…Interestingly, inhalation therapy using resveratrol as a senomorphic to treat respiratory disease shows that intratracheal administration preserves lung compliance and structure and prevents DNA damage in prematurely aging telomerase null ( terc -/-) mice ( 177 ). In addition, resveratrol-β-cyclodextrin inclusion complexes significantly suppresses ZnCl 2 smoke-induced acute lung injury through anti-inflammatory and anti-apoptotic mechanism ( 178 ).…”

First magnetic particle imaging to assess pulmonary vascular leakage in vivo in the acutely injured and fibrotic lung

“…A 2% Evans blue (Macklin, E808783) saline solution was prepared, and the tail vein was injected (20 mg/kg). 38 At 30 min post-injection, the mice were anesthetized by intraperitoneal injection of a mixture of 1.25% tribromoethanol and 2.5% 2-methyl-2-butanol. The chest cavity was exposed, and the abdominal aorta was excised.…”