Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
Volume 25, Issue 6
Displaying 1-7 of 7 articles from this issue
Feature articles “Application of Drug Delivery Systems to Oligonucleotide Therapeutics” Editor : Yoshinobu Takakura
  • Hiroaki Okada
    2010 Volume 25 Issue 6 Pages 552-564
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    A novel biomaterial of therapeutic oligonucleotides such as siRNA and miRNA exactly brought a new paradigm shift in the drug discovery. The technologies to overcome the off-target effects, enzymatic and membrane barrier for attaining a new medicine of these oligonucleotides are overviewed.
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  • Shinichi Mochizuki, Kazuo Sakurai
    2010 Volume 25 Issue 6 Pages 565-572
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    It has been demonstrated that β-1,3-glucans can form novel complexes with homo ODNs via a combination of hydrogen bonding and hydrophobic interactions. Dectin-1 is a major receptor involved in the recognition of β-glucans on APCs, including macrophages, dendritic cells, monocytes, neutrophils, and a subset of T cells. Therefore, the complex could be used to deliver an antisense ODN that can rectify abnormalities associated with inflammation. In this study, we show the application of the novel complex consisting of β-1,3-glucan and antisense oligonucleotide (AS-ODN) or CpG-DNA for drug delivery system. In-vivo, CpG-DNA/SPG induced robust type interferon responses dependently of Toll-like receptor 9. AS-ODN/SPG reduced the inflammation of dextran sulfate-induced colitis.
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  • Kohta Mohri, Makiya Nishikawa, Yuki Takahashi, Yoshinobu Takakura
    2010 Volume 25 Issue 6 Pages 573-578
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    Living organisms on the Earth use nucleic acids, which hybridize to complementary sequences to form double-stranded structures, to transfer genetic information to the next generations. This property of double-strand formation has been applied to construct a variety of DNA-based structures to open a novel research field of DNA nanotechnology. Our laboratory has shown that the immunostimulatory activity of oligodeoxynucleotide (ODN) containing CpG motifs, a well-known immunostimulator, can be greatly increased by building it up into Y-shaped DNA or dendrimer-like DNA.
    This article reviews the recent findings on these ODN-based nano-sized systems, which could find application to in vivo delivery of a variety of pharmaceutical compounds.
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  • Kazuyo Wada, Ryuichi Morishita
    2010 Volume 25 Issue 6 Pages 579-589
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    In recent years, nucleic acid medicines, such as antisense, decoy, siRNA and aptamer have been regarded as the targeted therapy for next generation. On the basis of many research results that elucidate functional mechanism of the nucleic acid medicines, efficacies of the medicines on various diseases have been verified and their development as pharmaceuticals and/or medical devices have been more and more expected. Besides, it is expected that application of the adequate DDS technique would enable to deliver the nucleic acid medicines to the targeted organ/tissue, which makes the medicines act on the targeted cell/molecule, and thus such application of the DDS technique would broaden indication of treatment by the nucleic acid medicines. However, there are several points to be considered in the development of the nucleic acid medicines, which are different from that of biologics and/or chemical drugs that do not have such concern generally. So, it is necessary for development of nucleic acid medicines to overcome such a variety of challenges.
    In this review, challenges in the development of nucleic acid medicines for pharmaceuticals and investigation of DDS application for medical devices are introduced, focusing on the clinical development of NFκB decoy oligodeoxynucleotides.
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  • Hidetaka Akita, Hiroto Hatakeyama, Hideyoshi Harashima
    2010 Volume 25 Issue 6 Pages 590-597
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    RNA interference (RNAi), discovered in the latter part of the 20th century is a promising technology for use in curing intractable genetic diseases by the sequence-specific cleavage of mRNA. Since incorporation of siRNA into the multi-protein RNA-Induced Silencing Complex (RISC) is a key process for siRNA activity, efficient cytoplasmic delivery system is essential for the application of siRNA in clinical use.
    In the present manuscript, we introduce our recent approach to control an intracellular trafficking of siRNA by means of multifunctional envelope-type nano device (MEND).
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  • Hidetoshi Arima, Keiichi Motoyama
    2010 Volume 25 Issue 6 Pages 598-606
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    Gene and oligonucleotide therapies are emerging as a potential strategy for the treatment of genetic diseases, cancers, cardiovascular diseases and infectious diseases. We have evaluated the potential use of various polyamidoamine (PAMAM) dendrimer (dendrimer, generation (G) 2-4) conjugates with cyclodextrins (CyDs) as novel DNA and RNA carriers. Among the various dendrimer conjugates with CyDs, the dendrimer (G3) conjugate with α-CyD having an average degree of substitution (DS) of 2.4 (α-CDE (G3, DS2.4)) displayed remarkable properties as DNA, shRNA and siRNA delivery carriers through the sensor function of α-CDEs toward nucleic acid drugs, cell surface and endosomal membranes. In an attempt to develop cell-specific gene transfer carriers, we prepared sugar-appended α-CDEs. Of the various sugar-appended α-CDEs prepared, galactose- or mannose-appended α-CDEs provided superior gene transfer activity to α-CDE in various cells, but not cell-specific gene delivery ability. However, lactose-appended α-CDE (Lac-α-CDE (G2)) was found to possess asialoglycoprotein receptor (AgpR)-mediated hepatocyte-selective gene and siRNA transfer activity both in vitro and in vivo. Most recently, we prepared folate-poly(ethylene glycol)-appended α-CDE (Fol-PαC (G3)) and revealed that Fol-PαC (G3) imparted folate receptor (FR)-mediated cancer cell-selective gene transfer activity. Consequently, α-CDEs bearing integrated, multifunctional molecules may possess the potential for DNA, shRNA and siRNA carriers.
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  • Naoki Makita, Shunji Nagahara
    2010 Volume 25 Issue 6 Pages 607-614
    Published: 2010
    Released on J-STAGE: February 25, 2011
    JOURNAL FREE ACCESS
    Recently, functional oligonucleotides, including siRNA and miRNA, draw much attention as candidates for novel medicine. Although siRNA and miRNA, which induce RNA interference, are powerful tools for regulating gene expression in vitro, it is not sufficient to apply them to clinical use, and efficient and safety delivery method is indispensable for practice. Atelocollagen-mediated nucleic acid delivery technology dramatically enhances the efficacy of siRNA and miRNA in vivo.
    In this review, we describe the effectiveness of atelocollagen-mediated DDS by introducing recent reports on its application for siRNA or miRNA.
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