title: Localized delivery of antisense oligonucleotides by cationic hydrogel suppresses TNF-α expression and endotoxin-induced osteolysis.
abstract: OBJECTIVE
  To investigate the possibility of using localized nucleic drug delivery methods for the treatment of osteolysis-related bone disease.
  
  
  METHODS
  A bio-degradable cationic hydrogel composed of gelatin and chitosan was used to deliver an antisense oligonucleotide (ASO) targeting murine TNF-α for the treatment of endotoxin-induced osteolysis.
  
  
  RESULTS
  ASO combined with this hydrogel was released when it was digested by adhering cells. The released ASO was efficiently delivered into contacted cells and tissues in vitro and in vivo. When tested in animal models of edotoxin-induced bone resorption, ASO delivered by such means effectively suppressed the expression of TNF-α and subsequently the osteoclastogenesis in vivo. Osteolysis in the edotoxin-induced bone resorption animal models was blocked by the treatment.
  
  
  CONCLUSIONS
  This is a successful attempt to apply localized gene delivery method to treat inflammatory diseases in vivo.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Huang
authors.forename: Xing
authors.initials: X
authors.lastname: Cai
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xiang
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Jiangning
authors.initials: J
authors.lastname: Chen
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005780:Gelatin / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D010012:Osteogenesis / Q000187:drug effects; D010014:Osteolysis / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002412:Cations; D004731:Endotoxins; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D048271:Chitosan