Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Sadikot, Ruxana T.; Kolanjiyil, Arun V.; Kleinstreuer, Clement; Rubinstein, Israel

Most of our work has focused on targeting macrophages and immune cells in lung injury. However, the vascular endothelium represents an important therapeutic target for lung injury, especially for systemic conditions such as sepsis. Several studies have focused on targeting the vascular endothelium, especially for molecules that are deficient or overexpressed in lung injury. Studies in animal models have investigated nanocarriers to target endothelial cells [38] . Shuvaev and Muzykantov [39] used vascular immune targeting to modulate reactive oxygen species producing enzymes by encapsulation in protease-resistant carriers. In a mouse model of LPS-induced lung injury, anti-PECAM liposomes loaded with EUK-134, a potent superoxide dismutase/catalase mimetic, enhanced targeting to the endothelium as compared to control IgG-coated liposomes. These liposomes alleviated LPSinduced lung injury, suggesting that anti-PECAM/EUK/liposome may be useful for alleviating acute pulmonary inflammation [40] . Ferrer et al. [41] used dexamethasone encapsulated in ICAM-1-targeted nanogels in a model of pulmonary inflammation. Nanogels are nanosized networks that can absorb large amounts of water while preserving their structure via physical or chemical crosslinks. In contrast to traditional nanoparticles, nanogels can deform to pass physiological filters, resulting in greater delivery efficiency than can be reached using stiffer nanoparticles. By using nanogels, they showed enhanced delivery of DEX to the lungs while reducing the toxicity of free DEX to nontarget organs and showed that the nanogels alleviate pulmonary inflammation. There is scant data that have targeted lung epithelium using a systemic approach. In a mouse model of LPS-induced lung injury, Lin et al. [42] tested polyethylenimine and DNA nanoparticles targeted to the β 2 -adrenergic receptor. Their study showed that treatment with polyethylenimine/ β 2 -adrenergic receptor improved survival of mice from 28 to 64% in lethal LPS-induced lung injury. Together, these studies show the potential of targeting specific molecules and cell types using a nanomedicine approach to mitigate lung injury and inflammation.