Drug Delivery System
Online ISSN : 1881-2732
Print ISSN : 0913-5006
ISSN-L : 0913-5006
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Volume 38, Issue 1
Drug Delivery System
Displaying 1-15 of 15 articles from this issue
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The new year's greetings
FOREWORD
OPINION
[Feature articles] “DDS for creating innovations in phamaceutical modalities” Editor:Makiya Nishikawa
  • Receptor mediated tissue targeted delivery of oligonucleotide
    Tetsuya Nagata, Takanori Yokota
    2023 Volume 38 Issue 1 Pages 8-14
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.8
    JOURNAL FREE ACCESS
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    Oligonucleotide therapeutics, represented by antisense and siRNA, are designed to bind to RNA by Watson-Crick base pairing. They are attracting attention as a new modality for treating diseases, especially hereditary and intractable diseases that have been difficult to treat in the past. The first two nucleic acid drugs on the market were both topically administered within the eye, followed by the first systemically administered oligonucleotide drug in 2013. Efficient delivery to target organs or cellwas one challenge. siRNA conjugated with N-acetylgalactosamine（GalNac）, which binds to a ligand on hepatocytes（ASGPR）, was developed and its usefulness was demonstrated in clinical trials. Now, four GalNac-siRNAs are on the market by 2022. The development of ligand-binding oligonucleotide drugs especially extra-hepatic target is expected to advance further in the future. Here, we review the current status of oligonucleotidedrug development, with a particular focus on ligand-directed development.
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  • Chemical synthesis of super messenger RNA medicine
    Mizuki Tada, Naoko Abe, Hiroshi Abe
    2023 Volume 38 Issue 1 Pages 15-23
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.15
    JOURNAL FREE ACCESS
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    Messenger RNA （mRNA） medicine was urgently approved in 2020 as a vaccine for COVID-19. However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.
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  • Oncolytic virus-induced activation of antitumor immunity and combination with cancer immunotherapy
    Fuminori Sakurai, Hiroyuki Mizuguchi
    2023 Volume 38 Issue 1 Pages 24-30
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.24
    JOURNAL FREE ACCESS
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    Much attention has been focused on oncolytic viruses, which specifically infect and kill tumor cells without apparent cytotoxicity in normal cells, as a novel anticancer agent. In 2021, a recombinant oncolytic herpesvirus simplex virus （HSV）-1 was approved in Japan（conditional and time-limited approval）. Recent studies demonstrated that oncolytic viruses induce not only activation of innate immunity, but also release of neoantigens and damage-associated molecular patterns（DAMPs） from infected tumor cells, leading to efficient activation of antitumor immunity, which contributes to the antitumor effects of oncolytic viruses. In addition, several studies reported that combination therapy of oncolytic viruses and cancer immunotherapy, including immune checkpoint inhibitors, exhibits superior synergistic therapeutic effects on various types of cancers. In this review, we introduce oncolytic virus-mediated activation of antitumor immunity and combination therapy with cancer immunotherapy.
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  • Cell therapeutics loaded with drug delivery system technology
    Kosuke Kusamori, Makiya Nishikawa
    2023 Volume 38 Issue 1 Pages 31-41
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.31
    JOURNAL FREE ACCESS
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    The recent diversification of modalities in drug discovery has been remarkable, and not only small molecule drugs and biopharmaceuticals but also oligonucleotide therapeutics and antibody-drug conjugates have been actively developed. Cell therapeutics is one of new drug modalities used in cell-based therapy, in which living cells are transplanted into patients, and has demonstrated the excellent therapeutic effects against various diseases including refractory diseases. On the other hand, the efficacy and safety of cell therapeutics are not still reliable and these issues need to be resolved for accelerating the development of cell therapeutics. In recent years, the technology of drug delivery system （DDS）, which is a methodology to optimize the therapeutic efficacy and safety of drugs, has been applied to cell therapeutics for the purpose of improving their efficacy and safety. In addition, the application of DDS technology to cell therapeutics opens the new cell-based therapy. In this article, we summarize the cell therapeutics that has been approved in Japan and review the recent findings of cell therapeutics loaded with DDS technology.
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  • In vitro BBB model derived from human iPS cells
    Tomoko Yamaguchi, Kenji Kawabata
    2023 Volume 38 Issue 1 Pages 42-48
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.42
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    The blood-brain barrier（BBB） constitutes the interface between the blood and the brain to prevent the invasion of pathogens and chemical substances. BBB also prevents the transport of drugs into the brain. Impairments of its barrier functions have been reported in case of some CNS diseases. In vitro BBB models are useful to understand the effects of CNS diseases on barrier functions and develop the novel CNS drugs. Brain microvascular cells differentiated from human iPS cells are used for in vitro BBB models to apply to the study of drug disposition, disease models, and drug delivery systems. Finally, the problems and improvements of current BBB models are mentioned.
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  • Development in Antibody-based Drug Delivery System Technology
    Etsuji Kaneko
    2023 Volume 38 Issue 1 Pages 49-57
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.49
    JOURNAL FREE ACCESS
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    Antibodies, which play a role in defense mechanisms from pathogens in human, have come to be widely used as a pharmaceutical platform due to their unique characteristics such as specific antigen recognition and high stability in vivo. Driving this trend are antibody engineering efforts to reduce antigenicity, enhance effector functions, reduce antibody molecular weight, and add multiple recognition capabilities, which have ultimately enabled antibodies to perform a variety of functions beyond simple neutralization of target antigens. In recent years, there have been many cases in which antibodies have been utilized as drug delivery tools by taking advantage of their most prominent feature, the ability to specifically recognize antigens. Drug delivery to tumor tissue and the central nervous system, which was once a major challenge in drug discovery, is being overcome, and antibody-based DDS is beginning to attract attention.
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  • Development of DDS using extracellular vesicles
    Yuki Takahashi
    2023 Volume 38 Issue 1 Pages 58-66
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.58
    JOURNAL FREE ACCESS
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    Extracellular Vesicles（EVs） are endogenous delivery carriers that deliver endogenous substances such as nucleic acids and proteins to the cells that take up EVs. Because of their nature as endogenous delivery carriers, development of EV-based DDS is expected. For the development of EV-based DDS, it is necessary to develop methods to produce and collect EVs, to load drugs onto EVs, and to control the pharmacokinetics of EVs in the body. Numerous research groups, including the author’s research group, have conducted research aimed at developing these methods. In this article, we would like to introduce the results of these studies that have been conducted toward the development of EV-based DDS, as well as the future prospects.
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Front line of DDS development in pharmaceutical industries
  • IZCARGOⓇ: the world's first biological drug applied with brain drug delivery technology
    Hiroyuki Sonoda, Kohtaro Minami
    2023 Volume 38 Issue 1 Pages 68-74
    Published: January 25, 2023
    Released on J-STAGE: April 25, 2023
    DOIhttps://doi.org/10.2745/dds.38.68
    JOURNAL FREE ACCESS
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    Most drugs cannot be delivered to the brain from the systemic circulation due to the presence of the blood-brain barrier, and therefore it is quite challenging to develop therapeutics addressing central nervous system disorders. IZCARGOⓇ（general name: pabinafusp alfa） is the world’s first biological drug applied with the brain drug delivery technology J-Brain CargoⓇ, which utilizes the transferrin receptor-mediated Fe/transferrin transport to the brain, and was launched in Japan in May 2021 to treat patients with all forms of MPS II. The drug is a fusion protein consisting of anti-human transferrin receptor antibody and iduronate-2-sulfatase and penetrates the blood-brain barrier into the brain parenchyma where it exerts pharmacological effects. J-Brain CargoⓇ is a fundamental technology for drug delivery to the central nervous system, and its application is expected to be expanded to various diseases.
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Tips for your DDS research
“Young Square” (mini review)
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