Atelocollagen-Mediated Systemic DDS for Nucleic Acid Medicines

Authors

  • KOJI HANAI,

    1. Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Osaka 567-0878 Japan (Formerly; Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd.)
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  • FUMITAKA TAKESHITA,

    1. National Cancer Center Research Institute, Tokyo 104-0045 Japan
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  • KIMI HONMA,

    1. Koken Bioscience Institute, Tokyo 115-0051 Japan
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  • SHUNJI NAGAHARA,

    1. Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Osaka 567-0878 Japan (Formerly; Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd.)
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  • MIHO MAEDA,

    1. Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Osaka 567-0878 Japan (Formerly; Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd.)
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  • YOSHIKO MINAKUCHI,

    1. Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Osaka 567-0878 Japan (Formerly; Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd.)
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  • AKIHIKO SANO,

    1. Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., Osaka 567-0878 Japan (Formerly; Formulation Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd.)
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  • TAKAHIRO OCHIYA

    1. National Cancer Center Research Institute, Tokyo 104-0045 Japan
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Address for correspondence: Koji Hanai, Formulation Laboratories, Technology Research and Development Center, Dainippon Sumitomo Pharma Co., Ltd., 3-45 Kurakakiuchi 1-chome, Ibaraki, Osaka 567-0878, Japan. Voice: +81-72-627-8146; fax: +81-72-627-8140.
 e-mail: koji-hanai@ds-pharma.co.jp

Abstract

Abstract: 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.

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