Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
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Volume 38, Issue 4
Drug Delivery System
Displaying 1-14 of 14 articles from this issue
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FOREWORD
OPINION
[Feature articles] “Glycan based DDS” Editor:Shino Manabe
  • Increased Target Cell Selectivity of Exosome Modified with Glycan Polymers
    Yutaka Inagaki, Yuki Matsuki, Takayo Yanagawa, Mitsuaki Goto, Toshihir ...
    2023 Volume 38 Issue 4 Pages 270-276
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.270
    JOURNAL FREE ACCESS
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    Exosomes are secreted from a variety of cells and transmit parental cell-derived biomolecules to recipient cells in distant organs. Although they are expected to serve as natural drug carriers, the use of exosomes as drug delivery tools is limited due to the low uptake efficiency by the target cells, degradation of the contents of exosome in the lysosome, and possible adverse effects caused by the delivery to non-target cells. Among them, target cell selectivity is most critical for developing exosome-based novel treatment modality. We are interested in the compositions of glycans on the surface of exosome that determine the selective delivery to target cells. For example, we have succeeded, by modifying exosomes with a lactose-carrying polymer, to enhance their selective delivery to parenchymal hepatocytes through asialoglycoprotein receptors that recognize galactose.
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  • Cyclodextrin-based supramolecular carriers for biopharmaceuticals
    Taishi Higashi
    2023 Volume 38 Issue 4 Pages 277-286
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.277
    JOURNAL FREE ACCESS
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    In recent years, active pharmaceutical ingredients have expanded from natural products and low-molecular-weight compounds to peptides, proteins, antibodies, nucleic acids, and genome-editing molecules, requiring advanced and diverse pharmaceutical technologies or DDS. In particular, the evolution and development speed of biopharmaceuticals are extremely fast；however, the levels of required formulation and DDS technology are extremely high. Therefore, designing optimal formulation and DDS carriers for each API leads to stagnation in drug development. In this review article, we introduce our recent supramolecular carriers, termed as transformable polymers, with the ultimate goal of developing DDS carriers that can be applied to all biopharmaceuticals.
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  • Cyclodextrin-porphyrin inclusion complexes that bind toxic gas components in the body for urinary excretion
    Hiroaki Kitagishi
    2023 Volume 38 Issue 4 Pages 287-296
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.287
    JOURNAL FREE ACCESS
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    Fire gas poisoning is the cause of about 40％ of deaths in fire accidents. The causative gases are carbon monoxide（CO） generated by incomplete combustion of wood materials and hydrogen cyanide（HCN） generated by the combustion of household materials such as acrylics and urethane. There is no clinically available drug for these gas poisonings, and thus many people are suffered each year. The author has developed an artificial hemoglobin-model compound, hemoCD, in the organic chemistry lab. HemoCD derivatives bind gaseou components such as CO and HCN in animals during circulation and excretes these gases as in the urine. This review article describes about hemoCD-Twins, a novel drug discovery seed that enables simultaneous detoxification of CO and HCN with a single administration.
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  • N-glycans bring therapeutic antibody
    Atsushi Yonezawa
    2023 Volume 38 Issue 4 Pages 297-304
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.297
    JOURNAL FREE ACCESS
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    Therapeutic antibodies play an important role in pharmacotherapy. The Asn297 residue of the Fc region is bound by an N-linked glycan, which plays an important role in pharmacodynamics and pharmacokinetics of therapeutic antibodies. In particular, terminal galactose, sialic acid and fucose are known to affect antibody-dependent cellular cytotoxicity （ADCC）, complement-dependent cytotoxicity （CDC） and liver uptake. N-glycans bring therapeutic antibody. On the other hand, the enzyme-linked immunosorbent assay （ELISA method） is mainly used to measure antibody drugs. It is impossible to detect the changes in sugar chains by ELISA method. Recent studies have been demonstrating that antibody drugs also undergo structural changes （biotransformation） in vivo. Novel analytical method using mass spectrometry technology is attracting attention. In this paper, we introduce the role of N-glycans in therapeutic antibodies and also our research.
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  • Studies on the drug delivery utilizing glycan-protein interactions
    Hiromune Ando
    2023 Volume 38 Issue 4 Pages 305-312
    Published: 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.305
    JOURNAL FREE ACCESS
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    Glycans are present on all cell surfaces and serve as intermediaries for communication with the outside world. Glycan-protein interaction is the central interaction, and various combinations of glycan-protein interactions have been found. The application of these interactions to drug delivery systems has been actively pursued for almost 40 years. In this article, we trace the history of research to date and review the research trends by organizing the research into two categories: research targeting cellular and tissue glycans and research targeting sugar-binding proteins （lectins）.
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  • Development of targeted siRNA delivery technologies by saccharide ligand conjugates
    Keiji Uehara
    2023 Volume 38 Issue 4 Pages 313-320
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.313
    JOURNAL FREE ACCESS
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    Nucleic acid-based medicines such as small interfering RNA（siRNA） and antisense oligonucleotides（ASOs） have great potential to address undruggable targets that use classical small-molecule approaches or traditional biologics. GalNAc-ligand-conjugated oligonucleotides, which targets the asialoglycoprotein receptor（ASGPR） on hepatocytes, is the most validated for targeted delivery of oligonucleotides, have been under evaluation in clinical trials for modulation of various liver-disease-related genes and includes several FDA-approved drugs. Given the success of GalNAc–oligonucleotides, ligand-conjugated oligonucleotides outside the liver are expected to create the novel drugs. However, receptor-mediated targeted delivery outside the liver using ligand-conjugated oligonucleotides remains challenging. We have investigated targeted delivery of siRNA to extrahepatic tissues/cells using glycan conjugated siRNA because we focused on unique binding properties between ligand and receptor result in enhancement of uptake amount of payloads into the cells. In this paper, we introduce a case study.
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Front line of DDS development in pharmaceutical industries
  • Drug for Duchenne muscular dystrophy ViltepsoⓇ
    Naoki Watanabe
    2023 Volume 38 Issue 4 Pages 322-328
    Published: September 25, 2023
    Released on J-STAGE: December 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.322
    JOURNAL FREE ACCESS
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    ViltepsoⓇ（viltolarsen） is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy （DMD）. It was discovered through joint research between Nippon Shinyaku Co., Ltd., and the National Center of Neurology and Psychiatry （NCNP）. It is an antisense oligonucleotide using phosphorodiamidate morpholino oligomer （PMO） that restores dystrophin protein lacking in DMD patients amenable to exon 53 skipping. VILTEPSO received marketing authorization under an accelerated approval pathway in Japan in March 2020. In the United States, it received accelerated approval from the US Food and Drug Administration （FDA） in August 2020.
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Tips for your DDS research
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