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Article ; Online: Gene and Oligonucleotide Delivery.

Kawakami, Shigeru / Arima, Hidetoshi

2022 Volume 46, Page(s) 100462

MeSH term(s)	Oligonucleotides ; Drug Delivery Systems
Chemical Substances	Oligonucleotides
Language	English
Publishing date	2022-04-25
Publishing country	England
Document type	Editorial
ZDB-ID	2095748-8
ISSN	1880-0920 ; 1347-4367 ; 0916-1139
ISSN (online)	1880-0920
ISSN	1347-4367 ; 0916-1139
DOI	10.1016/j.dmpk.2022.100462
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Article ; Online: Foreword.

Kawakami, Shigeru

Chemical & pharmaceutical bulletin

2017 Volume 65, Issue 7, Page(s) 611

Language	English
Publishing date	2017
Publishing country	Japan
Document type	Journal Article
ZDB-ID	213307-6
ISSN	1347-5223 ; 0009-2363
ISSN (online)	1347-5223
ISSN	0009-2363
DOI	10.1248/cpb.c17-ctf6507
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Zs.A 770: Show issues

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Article ; Online: Gait training with a safety suspension device accelerates the achievement of supervision level walking in subacute stroke: a randomized controlled trial.

Kawakami, Kenji / Miyasaka, Hiroyuki / Hioki, Yuichi / Furumoto, Ayako / Sonoda, Shigeru

International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation

2024 Volume 47, Issue 2, Page(s) 75–80

Abstract: Practicing walking in a safety suspension device allows patients to move freely and without excessive reliance on a therapist, which requires correcting errors and may facilitate motor learning. This opens the possibility that patients with subacute ... ...

Abstract	Practicing walking in a safety suspension device allows patients to move freely and without excessive reliance on a therapist, which requires correcting errors and may facilitate motor learning. This opens the possibility that patients with subacute stroke may improve their walking ability more rapidly. Therefore, we tested the hypothesis that overground gait training in a safety suspension device will result in achieving faster supervision-level walking than gait training without the suspension device. Twenty-seven patients with stroke admitted to the rehabilitation ward with functional ambulation categories (FAC) score of 2 at admission were randomly allocated to safety suspension-device group (SS group) or conventional assisted-gait training group (control group). In addition to regular physical therapy, each group underwent additional gait training for 60 min a day, 5 days a week for 4 weeks. We counted the days until reaching a FAC score of 3 and assessed the probability using Cox regression models. The median days required to reach a FAC score of 3 were 7 days for the SS group and 17.5 days for the control group, which was significantly different between the groups ( P < 0.05). The SS group had a higher probability of reaching a FAC score of 3 after adjusting for age and admission motor impairment (hazard ratio = 3.61, 95% confidence interval = 1.40-9.33, P < 0.01). The gait training with a safety suspension device accelerates reaching the supervision-level walking during inpatient rehabilitation. We speculate that a safety suspension device facilitated learning by allowing errors to be experienced and correct in a safe environment.
MeSH term(s)	Humans ; Male ; Stroke Rehabilitation/instrumentation ; Stroke Rehabilitation/methods ; Female ; Middle Aged ; Aged ; Walking ; Gait Disorders, Neurologic/rehabilitation ; Gait/physiology ; Stroke ; Exercise Therapy/instrumentation
Language	English
Publishing date	2024-04-09
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	533323-4
ISSN	1473-5660 ; 0342-5282
ISSN (online)	1473-5660
ISSN	0342-5282
DOI	10.1097/MRR.0000000000000625
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Zs.A 1326: Show issues

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Article ; Online: [Tackle Tough Questions of DDS].

Arima, Hidetoshi / Kawakami, Shigeru

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2020 Volume 140, Issue 5, Page(s) 609–610

MeSH term(s)	Drug Delivery Systems/methods ; Drug Delivery Systems/trends ; Humans
Language	Japanese
Publishing date	2020-05-07
Publishing country	Japan
Document type	Editorial
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.19-00218-F
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Zs.A 643: Show issues

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Article ; Online: Development of Triple-Negative Breast Cancer-Targeted Liposomes with MUC16 Binding Peptide Ligand in Triple-Negative Breast Cancer Cells.

Hagimori, Masayori / Kato, Naoya / Orimoto, Akira / Suga, Tadaharu / Kawakami, Shigeru

Journal of pharmaceutical sciences

2023 Volume 112, Issue 6, Page(s) 1740–1745

Abstract: Triple-negative breast cancer (TNBC) is a highly malignant tumor that does not express the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2). As molecular approaches to these targets have limited ... ...

Abstract	Triple-negative breast cancer (TNBC) is a highly malignant tumor that does not express the estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2). As molecular approaches to these targets have limited clinical utility in TNBC, novel strategies for the treatment of TNBC are urgently needed. MUC16 (Mucin-16) is a glycoprotein involved in cell proliferation and apoptosis and is overexpressed in breast cancer. To develop a clinically available strategy for TNBC treatment, we synthesized a MUC16 targeted peptide (EVQ)-grafted lipid derivative, EVQ-(SG)
MeSH term(s)	Humans ; Liposomes/chemistry ; Triple Negative Breast Neoplasms/drug therapy ; Ligands ; CA-125 Antigen/therapeutic use ; Cell Line, Tumor ; Peptides/therapeutic use ; Drug Carriers ; Lipids/chemistry ; Polyethylene Glycols/chemistry ; Membrane Proteins
Chemical Substances	Liposomes ; Ligands ; CA-125 Antigen ; Peptides ; Drug Carriers ; Lipids ; Polyethylene Glycols (3WJQ0SDW1A) ; MUC16 protein, human ; Membrane Proteins
Language	English
Publishing date	2023-03-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1016/j.xphs.2023.02.025
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Article ; Online: Influence of lipid composition of messenger RNA-loaded lipid nanoparticles on the protein expression via intratracheal administration in mice.

Geng, Longjian / Kato, Naoya / Kodama, Yukinobu / Mukai, Hidefumi / Kawakami, Shigeru

International journal of pharmaceutics

2023 Volume 637, Page(s) 122896

Abstract: Intratracheal (i.t.) administration, which takes advantage of the specific structure of the respiratory system, can effectively deliver nanoparticles to the lung. Much remains unknown about the i.t. administration of messenger RNA (mRNA)-lipid ... ...

Abstract	Intratracheal (i.t.) administration, which takes advantage of the specific structure of the respiratory system, can effectively deliver nanoparticles to the lung. Much remains unknown about the i.t. administration of messenger RNA (mRNA)-lipid nanoparticles (LNPs) and the effect of lipid composition. In this study, we administered minute amounts of mRNA-LNP solutions into mice intratracheally and investigated the effect of lipid composition on protein expression in the lungs. We first validated higher protein expression with mRNA-LNP compared to that with mRNA-PEI complex and naked mRNA. Then, we evaluated the influence of lipid composition of LNPs on the protein expression and found that: 1) decreasing the PEG molarity from 1.5% to 0.5% could significantly increase the protein expression; 2) replacing DMG-PEG with DSG-PEG could slightly increase the protein expression; 3) using DOPE instead of DSPC could increase protein expression by an order of magnitude. We successfully prepared an mRNA-LNP with optimal lipid compositions that led to robust protein expression following i.t. administration, thus providing meaningful insights into advanced development of mRNA-LNPs for therapeutic i.t. administration.
MeSH term(s)	Animals ; Mice ; Lipids/chemistry ; RNA, Messenger/metabolism ; Liposomes ; Nanoparticles/chemistry ; RNA, Small Interfering
Chemical Substances	Lipid Nanoparticles ; Lipids ; RNA, Messenger ; Liposomes ; RNA, Small Interfering
Language	English
Publishing date	2023-03-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	428962-6
ISSN	1873-3476 ; 0378-5173
ISSN (online)	1873-3476
ISSN	0378-5173
DOI	10.1016/j.ijpharm.2023.122896
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Zs.A 1409: Show issues

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Article ; Online: Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics.

Mukai, Hidefumi / Ogawa, Koki / Kato, Naoya / Kawakami, Shigeru

Drug metabolism and pharmacokinetics

2022 Volume 44, Page(s) 100450

Abstract: Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery ... ...

Abstract	Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.
MeSH term(s)	COVID-19/therapy ; Gene Editing ; Humans ; Lipids ; Liposomes ; Nanoparticles ; RNA, Messenger/genetics
Chemical Substances	Lipid Nanoparticles ; Lipids ; Liposomes ; RNA, Messenger
Language	English
Publishing date	2022-02-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2095748-8
ISSN	1880-0920 ; 1347-4367 ; 0916-1139
ISSN (online)	1880-0920
ISSN	1347-4367 ; 0916-1139
DOI	10.1016/j.dmpk.2022.100450
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Zs.A 3734: Show issues

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Article ; Online: The Molecular Basis of Heat-Stable Enterotoxin for Vaccine Development and Cancer Cell Detection.

Goto, Masaya / Yoshino, Shinya / Hiroshima, Kyona / Kawakami, Toru / Murota, Kaeko / Shimamoto, Shigeru / Hidaka, Yuji

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 3

Abstract: Heat-stable enterotoxin ( ... ...

Abstract	Heat-stable enterotoxin (ST
MeSH term(s)	Humans ; Enterotoxins/genetics ; Enterotoxins/chemistry ; Bacterial Toxins/genetics ; Bacterial Toxins/chemistry ; Hot Temperature ; Caco-2 Cells ; Enterotoxigenic Escherichia coli/genetics ; Enterotoxigenic Escherichia coli/metabolism ; Peptides/metabolism ; Escherichia coli Proteins ; Vaccine Development ; Disulfides ; Guanylate Cyclase/metabolism ; Neoplasms
Chemical Substances	Enterotoxins ; Bacterial Toxins ; Peptides ; Escherichia coli Proteins ; Disulfides ; Guanylate Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2023-01-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28031128
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Article ; Online: Investigation of enhanced intracellular delivery of nanomaterials modified with novel cell-penetrating zwitterionic peptide-lipid derivatives.

Sugimoto, Yuri / Suga, Tadaharu / Umino, Mizuki / Yamayoshi, Asako / Mukai, Hidefumi / Kawakami, Shigeru

Drug delivery

2023 Volume 30, Issue 1, Page(s) 2191891

Abstract: Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of ... ...

Abstract	Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)
MeSH term(s)	Liposomes ; Drug Delivery Systems ; Nanoparticles ; Cell-Penetrating Peptides ; Lipids ; RNA, Messenger
Chemical Substances	Liposomes ; Cell-Penetrating Peptides ; Lipids ; RNA, Messenger
Language	English
Publishing date	2023-03-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1213261-5
ISSN	1521-0464 ; 1071-7544
ISSN (online)	1521-0464
ISSN	1071-7544
DOI	10.1080/10717544.2023.2191891
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Zs.A 4252: Show issues

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Article ; Online: [Development of Nano-DDS Carriers for Control of Spatial Distribution Using Multi-color Deep Imaging].

Kawakami, Shigeru / Suga, Tadaharu

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2020 Volume 140, Issue 5, Page(s) 633–640

Abstract: Because active-targeted liposomes are very complex formulations, quality characteristics of functional lipids have not been defined yet, and this is a major obstacle in clinical application of active targeted liposomes. We have developed high ... ...

Abstract	Because active-targeted liposomes are very complex formulations, quality characteristics of functional lipids have not been defined yet, and this is a major obstacle in clinical application of active targeted liposomes. We have developed high functionality and quality (HFQ) lipids, which define quality characteristics of functional lipids for clinical drug delivery system (DDS) applications. Because HFQ lipids are designed to enable facile and rapid functionalization of DDS carrier by simple and one-step mixing, we are expanding applications for not only liposomes but also exosomes and cells. Recently, we developed multi-color deep imaging by tissue clearing for analysis of spatial distribution of DDS in various tissues. Nanocarriers are usually non-uniformly distributed in solid tumors because of their heterogeneity. Especially, in refractory cancer such as pancreatic cancer, the presence of collagen and blood vessels greatly affects intra-tumor distribution of DDS carrier. Therefore information on spatial relations between the tissue structure and DDS carrier is important to regulate precisely intra-tumor distribution of DDS carrier. Recently, our group has established multi-color deep imaging to analyze spatial distribution of stromal collagen, liposomes, and blood vessels in pancreatic tumor tissue. In this review, we present recent research in developing HFQ lipids. Moreover, current status of research on DDS for pancreatic cancer treatment is reviewed.
MeSH term(s)	Drug Carriers ; Drug Delivery Systems/methods ; Drug Development ; Humans ; Liposomes ; Molecular Imaging/methods ; Nanoparticles ; Pancreatic Neoplasms/metabolism ; Tissue Distribution
Chemical Substances	Drug Carriers ; Liposomes
Language	Japanese
Publishing date	2020-05-07
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.19-00218-4
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