Localized delivery of antisense oligonucleotides by cationic hydrogel suppresses TNF-α expression and endotoxin-induced osteolysis.

PURPOSE: 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.

CONCLUSION

This is a successful attempt to apply localized gene delivery method to treat inflammatory diseases in vivo.