A new collaborative study led by researchers Drs. Saguna Verma and Juwon Park, at the University of Hawai‘i at Mānoa, and Dr. Wooram Park at Sungkyunkwan University, South Korea, have developed an innovative drug delivery system that may help reduce severe lung injury. The findings were recently published in the
Journal of Controlled Release (2025 Jun 10;382:113736. doi: 10.1016/j.jconrel.2025.113736), a leading journal in drug delivery and biomaterials research with an impact factor of 11.467.
The research team engineered a specialized lipid nanoparticle (LNPs) drug delivery system capable of carrying and delivering two drugs directly to the neutrophils in the lungs. Using SARS-CoV-2 as a model to study role of neutrophil-associated inflammatory responses in driving lung injury, the team demonstrated that the these LNPs only targeted lung neutrophils, did not cause any toxicity, and efficiently suppressed lung inflammation, and early signs of fibrosis in infected mice. The experiments were conducted at JABSOM’s high-containment biosafety facility (ABSL-3/BSL3), which enabled researchers to conduct this cutting-edge study. This study shows the first successful attempt to deliver two NET-inhibiting drugs, DNase I and Sivelestat, together in a cell-specific and lung-targeted manner using an advanced nanoparticle platform.
Activated neutrophils are one of the drivers of lung injury in COVID-19“We know that excessive neutrophil activation and neutrophil extracellular trap (NET) formation contribute to lung injury and long-term complications. NETs play a crucial role in defending the host against infections. However, excessive or uncontrolled NET formation can contribute to the severity of COVID-19 and has been recognized as a potential therapeutic target for COVID-19–associated acute lung injury. Although drugs that block NETs exist, they often require high doses due to instability in the body and nonspecific off-target effects. Our new approach overcomes these limitations by delivering both drugs directly to lung neutrophils using lipid nanoparticles, which improves drug effectiveness and minimizes side effects,” said Dr. Park.
“This project is a great example of how interdisciplinary research can facilitate the development of novel drug delivery platforms and evaluate their efficiency in animal models. Recently, LNP-based selective organ targeting (SORT) has been developed for specifically targeting the liver, lung, or spleen. However, the strength of this study is that our LNPs are designed not only to target the lung but specifically to lung neutrophils,” said Dr. Verma.
The research team believes this lipid nanoparticle platform could also be adapted to target other inflammatory immune cells in the lung or deliver different drugs. The researchers aim to investigate the therapeutic potential of these LNPs in other acute respiratory conditions, including influenza and sepsis.
