title: Delivery of the high-mobility group box 1 box A peptide using heparin in the acute lung injury animal models.
abstract: In this study, the efficacy of the high-mobility group box-1 box A (HMGB1A)/heparin complex was evaluated for the treatment of acute lung injury (ALI). HMGB1A is an antagonist against wild-type high-mobility group box-1 (wtHMGB1), a pro-inflammatory cytokine that is involved in ALIs. HMGB1A has positive charges and can be captured in the mucus layer after intratracheal administration. To enhance the delivery and therapeutic efficiency of HMGB1A, the HMGB1A/heparin complex was produced using electrostatic interactions, with the expectation that the nano-sized complex with a negative surface charge could efficiently penetrate the mucus layer. Additionally, heparin itself had an anti-inflammatory effect. Complex formation with HMGB1A and heparin was confirmed by atomic force microscopy. The particle size and surface charge of the HMGB1A/heparin complex at a 1:1 weight ratio were 113nm and -25mV, respectively. Intratracheal administration of the complex was performed into an ALI animal model. The results showed that the HMGB1A/heparin complex reduced pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, more effectively than HMGB1A or heparin alone. Hematoxylin and eosin staining confirmed the decreased inflammatory reaction in the lungs after delivery of the HMGB1A/heparin complex. In conclusion, the HMGB1A/heparin complex might be useful to treat ALI.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Song
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Chunxian
authors.initials: C
authors.lastname: Piao
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Seonyeong
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea.
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Song
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Chungnam National University, Daejeon 305-764, Korea.
authors.forename: Joon Sig
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Korea. Electronic address: minhyung@hanyang.ac.kr.
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002460:Cell Line; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage* / Q000627:therapeutic use; D024243:HMGB1 Protein / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D006493:Heparin / Q000008:administration & dosage* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D011994:Recombinant Proteins; D013499:Surface Properties
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D024243:HMGB1 Protein; D010455:Peptides; D011994:Recombinant Proteins; D006493:Heparin
keywords: Acute lung injury; Complex; Heparin; High-mobility group box-1; Inflammation