title: Antioxidant polymeric nanoparticles as novel therapeutics for airway inflammatory diseases.
abstract: 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.
authors.affiliation: Department of BIN Fusion Technology, Chonbuk National University, Jeonju 561-756, Republic of Korea.
authors.forename: Donghyuck
authors.initials: D
authors.lastname: Yoo
authors.forename: Kyeonghye
authors.initials: K
authors.lastname: Guk
authors.forename: Hyungmin
authors.initials: H
authors.lastname: Kim
authors.forename: Gilson
authors.initials: G
authors.lastname: Khang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
mesh_terms: D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000975:Antioxidants / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001592:Benzyl Alcohols / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000276:immunology; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010047:Ovalbumin; D011108:Polymers / Q000737:chemistry*
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D016207:Cytokines; D011108:Polymers; D010047:Ovalbumin