Injectable polyplex hydrogel for localized and long-term delivery of siRNA.
Here, we describe a concept for localized and long-term delivery of short interfering RNA (siRNA) using an injectable polyplex hydrogel possessing thermosensitivity and biodegradability properties. We prepared a low molecular weight polyethyleneimine-poly(organophosphazene) conjugate as a thermosensitive and cationic polymer that has a cleavable ester linkage. The conjugates formed about 100 nm sized polyplexes with siRNAs, and the polyplex solution turned into a polyplex hydrogel at body temperature via a hydrophobic interaction. We injected the polyplex hydrogel with siRNA of cyclin B1, an essential protein for controlling the cell cycle, into the tumor xenograft model. Polyplexes were slowly released from the polyplex hydrogel by dissolution and degradation, allowing an in vivo antitumor effect via cyclin B1 gene silencing for 4 weeks with only a single injection.
Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Young-Min
YM
Kim
Mi-Ran
MR
Park
Soo-Chang
SC
Song
D000818:Animals; D045744:Cell Line, Tumor; D056744:Cyclin B1 / Q000037:antagonists & inhibitors / Q000235:genetics; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D020868:Gene Silencing; D006801:Humans; D020100:Hydrogels; D007267:Injections; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008970:Molecular Weight; D058726:Nanoconjugates / Q000737:chemistry; D036103:Nanotechnology; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D010316:Particle Size; D044367:Phase Transition; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D014783:Viscosity; D023041:Xenograft Model Antitumor Assays
D056744:Cyclin B1; D003692:Delayed-Action Preparations; D020100:Hydrogels; D058726:Nanoconjugates; D009943:Organophosphorus Compounds; D011108:Polymers; D034741:RNA, Small Interfering; C515246:poly(organophosphazene); D011094:Polyethyleneimine