Antioxidant polymeric nanoparticles as novel therapeutics for airway inflammatory diseases

Successful pulmonary drug delivery requires polymeric drug delivery systems which have excellent biocompatibility and fast degradation rates, when frequent administration is necessary. Here, we report a new family of fully biodegradable hydroxybenzyl alcohol (HBA)-incorporated polyoxalate (HPOX) as a novel therapeutics of airway inflammatory diseases. HPOX was designed to incorporate antioxidant and anti-inflammatory HBA and peroxalate ester linkages capable of reacting with hydrogen peroxide (H₂O₂) in its backbone. HPOX nanoparticles exhibited highly potent antioxidant and anti-inflammatory effects by scavenging H₂O₂, reducing the generation of intracellular oxidative stress and suppressing the expression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin (IL)-1β in stimulated macrophages. The potential of HPOX nanoparticles as an anti-asthmatic agent was evaluated using a murine model of asthma. Intratracheal administration of HPOX nanoparticles remarkably reduced the recruitment of inflammatory cells and expression of pro-inflammatory mediators such as IL-4 and iNOS. Based on their excellent antioxidant, anti-inflammatory and anti-asthmatic activities, we believe that HPOX nanoparticles have great potential as therapeutics and drug carriers for the treatment of airway inflammatory diseases such as asthma.