Atelocollagen-mediated systemic DDS for nucleic acid medicines.
The goal of our research is to provide a practical platform for drug delivery in oligonucleotide therapy. We report here the efficacy of an atelocollagen-mediated oligonucleotide delivery system applied to systemic siRNA and antisense oligonucleotide treatments in animal disease models. Atelocollagen and oligonucleotides formed a complex of nanosized particles, which was highly stable against nucleases. The complex allowed oligonucleotides to be delivered efficiently into several organs and tissues via intravenous administration. In a tumor metastasis model, the complex successfully delivered siRNA to metastasized tumors in bone tissue and inhibited their growth. We also demonstrated that a single intravenous treatment of the antisense oligodeoxynucleotide complex suppressed ear dermatitis in a contact hypersensitivity model. These results indicate the strong potential of the atelocollagen-mediated drug delivery system for practical therapeutic technology.
Hanai
Koji
K
Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Ibaraki, Osaka 567-0878, Japan. koji-hanai@ds-pharma.co.jp
Takeshita
Fumitaka
F
Honma
Kimi
K
Nagahara
Shunji
S
Maeda
Miho
M
Minakuchi
Yoshiko
Y
Sano
Akihiko
A
Ochiya
Takahiro
T
D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary; D003094:Collagen / Q000627:therapeutic use*; D003872:Dermatitis / Q000628:therapy; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009841:Oligonucleotides / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014018:Tissue Distribution
D004337:Drug Carriers; D009841:Oligonucleotides; D034741:RNA, Small Interfering; C059821:atelocollagen; D003094:Collagen