type: misc

label: url

en: ビタミンEエステル体の抗肥満薬としての可能性

ja: ビタミンEエステル体の抗肥満薬としての可能性

en: バイオインダストリー

ja: バイオインダストリー


en: Intradermal delivery of drugs by weak electric current

ja: 微弱電流による薬剤の皮内送達

en: Chemical engineering

ja: 化学工学


en: Biomimetic nanoparticle drug delivery systems to overcome biological barriers for therapeutic applications.

en: Targeted drug delivery using nanoparticles has been applied for the treatment of diverse diseases, including cancer and inflammatory diseases. Nanoparticle-mediated delivery of therapeutic agents via the enhanced permeability and retention effect generally augments their therapeutic efficiency; however, limitations with passive entry of nanoparticles into diseased sites, due to the presence of biological barriers represented by the endothelial layer, remain to be addressed. To this end, development of nanoparticles with intrinsic characteristics similar to circulatory cells (e.g., leukocytes, platelets) for use as biomimetic drug delivery systems (DDS) has been focused as a means to overcome the issues of conventional DDS. In particular, synthetic biomimetic nanoparticles coated with cellular membranes were recently prepared and shown to actively overcome the inflamed vessels and tumor microenvironment as a result of the functionality of membrane proteins, which allowed secure drug delivery into diseased sites. We recently developed liposomes modified with leukocyte membrane proteins via intermembrane protein transfer, a simple method to reconstitute cellular membrane proteins onto lipid bilayers. The resultant liposomes demonstrated the ability to cross the inflamed endothelial layer and permeate into tumor tissue by mimicking the properties of leukocytes. Thus, biomimetic DDS offer promise as new therapeutic approaches for various diseases by overcoming biological barriers that typically inhibit drug delivery. Herein, we review recent approaches to develop biomimetic DDS using the cell membrane coating method, and highlight our recent findings on leukocyte-mimetic liposomes prepared via intermembrane protein transfer.

en: Chemical & Pharmaceutical Bulletin

ja: Chemical & Pharmaceutical Bulletin


en: Iontophoresis of Biological Macromolecular Drugs.

en: Over the last few decades, biological macromolecular drugs (e.g., peptides, proteins, and nucleic acids) have become a significant therapeutic modality for the treatment of various diseases. These drugs are considered superior to small-molecule drugs because of their high specificity and favorable safety profiles. However, such drugs are limited by their low oral bioavailability and short half-lives. Biological macromolecular drugs are typically administrated via invasive methods, e.g., intravenous or subcutaneous injections, which can be painful and induce needle phobia. Noninvasive transdermal delivery is an alternative administration route for the local and systemic delivery of biological macromolecular drugs. However, a challenge with the noninvasive transdermal delivery of biological macromolecular drugs is the outermost layer of the skin, known as the stratum corneum, which is a physical barrier that restricts the entry of extraneous macromolecules. Iontophoresis (IP) relies on the application of a low level of electricity for transdermal drug delivery, in order to facilitate the skin permeation of hydrophilic and charged molecules. The IP of several biological macromolecular drugs has recently been investigated. Herein, we review the IP-mediated noninvasive transdermal delivery of biological macromolecular drugs, their routes of skin permeation, their underlying mechanisms, and their advance applications.

en: Pharmaceutics

ja: Pharmaceutics


en: Application and utility of liposomal neuroprotective agents and biomimetic nanoparticles for the treatment of ischemic stroke

en: Ischemic stroke is still one of the leading causes of high mortality and severe disability worldwide. Therapeutic options for ischemic stroke and subsequent cerebral ischemia/reperfusion injury remain limited due to challenges associated with drug permeability through the blood-brain barrier (BBB). Neuroprotectant delivery with nanoparticles, including liposomes, offers a promising solution to address this problem, as BBB disruption following ischemic stroke allows nanoparticles to pass through the intercellular gaps between endothelial cells. To ameliorate ischemic brain damage, a number of nanotherapeutics encapsulating neuroprotective agents, as well as surface-modified nanoparticles with specific ligands targeting the injured brain regions, have been developed. Combination therapy with nanoparticles encapsulating neuroprotectants and tissue plasminogen activator (t-PA), a globally approved thrombolytic agent, has been demonstrated to extend the narrow therapeutic time window of t-PA. In addition, the design of biomimetic drug delivery systems (DDS) employing circulating cells (e.g., leukocytes, platelets) with unique properties has recently been investigated to overcome the injured BBB, utilizing these cells' inherent capability to penetrate the ischemic brain. Herein, we review recent findings on the application and utility of nanoparticle DDS, particularly liposomes, and various approaches to developing biomimetic DDS functionalized with cellular membranes/membrane proteins for the treatment of ischemic stroke.


en: Transdermal drug delivery by iontophoresis

ja: イオントフォレシスによる経皮デリバリー

en: Functional macromolecules, such as siRNA, are expected as the ideal drugs to induce immune response and suppress specific genes for therapy of skin disorders and cancer. However, delivery of the macromolecules into skin is difficult due to large molecular weight and high hydrophilicity. Since iontophoresis is known to accelerate transdermal permeation of charged molecules by applying a weak electric current to the skin, we paid attention to iontophoresis as an ideal technology for transdermal delivery, and attempted transdermal delivery of macromolecules. siRNA is expected as novel nucleic acid medicines. Thus, we examined iontophoresis of naked siRNA on rat skin in vivo. Naked siRNA was effectively accumulated in the skin after iontophoresis. In addition, iontophoretic delivery of siRNA significantly reduced the target mRNA. From this result, it was suggested that siRNA was delivered into not only the skin tissue, but also cytoplasm of target cells. Then, we analyzed the in vitro intracellular delivery of fluorescent-labeled siRNA by weak electric current(WEC), and found that cellular uptake of fluorescent-labeled siRNA was increased by WEC, while endocytosis inhibitors significantly prevented siRNA uptake. These results indicate that the cellular uptake mechanism by WEC is endocytosis. Moreover, we compared the intracellular trafficking of macromolecule FITC-dextran, which has different molecular weight, 10,000 and 70,000, taken up by weak electric current. The 10,000 dextran spread to cytoplasm, but 70,000 dextran remained in endosome/lysosomes. This result suggested that WEC treatment induced very unique endosome that leaked macromolecules with a molecular weight of less than 70,000. Transmission electron microscopy of cells treated by WEC showed that the WEC-induced endosomes exhibited an elliptical shape. In the WEC-induced endosomes, ceramide, which makes pore structures in the membrane, was localized. Interestingly, we found that WEC accelerates the production of exosomes as a result of stimulation of the endocytosis. In this review, we also introduce recent findings regarding IP-mediated transdermal drug delivery of bio-macromolecules such as antibody and WEC-mediated increases in vascular permeability.

ja: イオントフォレシス(IP)は，微弱電流を用いる経皮デリバリー技術であるが，従来その適用は荷電を有する疎水性化合物に限定され，親水性高分子はIPに適用できないと考えられてきた．しかし筆者らは，核酸医薬siRNAなどのIPによる経皮デリバリーに成功した．メカニズム解析の結果，微弱電流処理により，細胞シグナル系が活性化されて皮膚組織細胞間隙が開裂することで，高分子が皮内に浸透可能になること，さらに，エンドサイトーシスが誘起され細胞質まで送達されることが明らかになってきた．また，微弱電流によってエクソソーム分泌が促進されることも見出している．本稿では，最近の知見も交えてIPによる経皮デリバリーについて紹介する．

en: Drug Delivery System

ja: Drug Delivery System


en: Noninvasive transdermal delivery of liposomes by weak electric current.

en: Noninvasive transdermal drug delivery (NTDD) offers an exciting new method of administration relative to conventional routes, but is associated with some challenges. Liposomes are capable of encapsulating transdermally-unfavorable drugs. However, the horny layer of skin is a significant barrier that limits efficient transdermal delivery of liposomes. Iontophoresis using weak electric current (WEC) represents a NTDD technology. WEC treatment of liposomes applied to the skin surface improves transdermal penetration of encapsulated drugs by cooperative effects. In this review, we provide an overview of the application of WEC/liposomes for transdermal delivery of macromolecules and low molecular weight drugs. We compare the transdermal delivery and therapeutic efficiency of the combined system with conventional routes of administration and their individual use. We discuss a novel perspective on the mechanism of WEC-mediated transdermal delivery of liposomes, which suggests that WEC activates the intracellular signaling pathway for transdermal permeation and induces unique endocytosis in skin cells.

en: Advanced Drug Delivery Reviews

ja: Advanced Drug Delivery Reviews


en: [Drug Delivery to Various Body Organs via Non-blood Circulatory Pathway].

en: Delivery of nucleic acid therapeutics to target body organs requires injection of nanocarriers into the bloodstream. However, as such nanocarriers would also be delivered to non-target organs, low delivery efficiency to target organs and risk of unexpected effects are clear limitations of this technology. We recently applied iontophoresis (IP) for direct delivery of nucleic acid therapeutics to various organs. IP relies on a weak electric current for noninvasive transdermal drug delivery. We found that IP can deliver hydrophilic macromolecules and nanoparticles into the skin. We previously succeeded in transdermal delivery of siRNA, and subsequent knockdown (70%) of target mRNA levels in the skin via IP of siRNA (Int. J. Pharm., 383, 2010, Kigasawa et al.). Moreover, we found that cell signal activation and cleavage of intercellular junctions are induced by IP (J. Biol. Chem., 289, 2014, Hama et al.). We hypothesized that this phenomenon should be observed in not only skin but also other organs, and subsequently carried out IP of nucleic acid therapeutics to various body organs including liver, pancreas and kidney. This technique resulted in delivery of nucleic acid therapeutics into the various target body organs, and subsequent knockdown of target genes. These results suggest that direct delivery to target body organs via non-blood circulatory pathway is possible. This technology may offer a solution to the various limitations associated with current drug delivery systems (DDS).

en: Journal of the Pharmaceutical Society of Japan

ja: 薬学雑誌


en: イオントフォレシスによる核酸医薬の展開-微弱電流による組織細胞生理の制御

ja: イオントフォレシスによる核酸医薬の展開-微弱電流による組織細胞生理の制御

en: Journal of Clinical and Experimental Medicine

ja: 医学のあゆみ


en: アスタキサンチンのヘマトコッカス培養による生産と機能性研究

ja: アスタキサンチンのヘマトコッカス培養による生産と機能性研究

en: アグリバイオ

ja: アグリバイオ


en: ビタミンE コハク酸の多彩な生理作用と薬学への展開

ja: ビタミンE コハク酸の多彩な生理作用と薬学への展開

en: Vitamins

ja: ビタミン


en: Control of Tissue and Cellular Physiology by Faint Electricity for Delivery of Nanomedicine

ja: ナノメディシン送達のための微弱電流による組織細胞生理の制御

en: Chemical Industry

ja: 化学工業


en: Enhancement of Nitric Oxide and Superoxide Generations by α-Tocopheryl Succinate and Its Apoptotic and Anticancer Effects

en: Tocopheryl succinate (TS), a succinyl ester of alpha-tocopherol (alpha-T), has been reported to have various biological activities. In this communication, we review the current findings about TS including our recent studies of its effects on nitric oxide (NO) and superoxide (O2-) generations implicated in cancer and atherosclerosis. First, we investigated the effect of TS on NO production in vascular smooth muscle cells (VSMC) under atherosclerosis-like conditions using lipopolysaccharide (LPS) and interferon-gamma (IFN). TS enhanced LPS/IFN-dependent NO production, but alpha-T itself did not. The enhancement by TS of NO production was inhibited by alpha-T but not by antioxidants such as ascorbic acid and 2[3]-t-butyl-4-hydroxyanisole (BHA). TS enhanced the amount of protein kinase Calpha (PKCalpha) in VSMC, and PKC inhibitors inhibited TS-enhanced NO production, suggesting that the enhancing effect of TS on NO production is caused by up-regulation of PKC. Second, we found that TS induced apoptosis in VSMC associated with increase in O2- generation via NADPH-dependent oxidase. We further observed that a mouse breast cancer cell line C127I was more susceptible for TS-induced apoptosis than a mouse breast normal cell line NmuMG, and that superoxide dismutase, alpha-T, and BHA inhibited TS-caused morphological cell damage in C127I. From these results, O2- itself and/or other reactive oxygen species are assumed to associate with TS-induced cell toxicity, and antioxidative defense systems are supposed to be lowered in cancer cells. Finally, we found that intravenous injection of TS vesicles completely inhibited the growth of melanoma cells B16-F1 inoculated on the back of hairless mice and enhanced their survival time.

en: Biochemistry (Moscow)

ja: Biochemistry (Moscow)


en: Tocopheryl succinate-versatile function due to its unique physicochemical properties

en: Journal of Clinical Biochemistry and Nutrition


en: ビタミンEコハク酸 : アポトーシス誘導作用と抗ガン剤としての可能性

ja: ビタミンEコハク酸 : アポトーシス誘導作用と抗ガン剤としての可能性


en: 喫煙が血液中で悪玉リン脂質をつくるー動脈硬化との関連ー

ja: 喫煙が血液中で悪玉リン脂質をつくるー動脈硬化との関連ー

en: 日本薬学会 第122年会講演ハイライト

ja: 日本薬学会 第122年会講演ハイライト


en: Platelet-activating factor (PAF)- like oxidized phospholipids: relevance to atherosclerosis

en: Lipid peroxidation is involved in the pathogenesis of chronic diseases including atherosclerosis. Oxidized lipoprotein has diverse biological activities and is believed to initiate atheroma formation and maturate fatty plaque. The active components of oxidized lipoproteins still remain to be clarified, but a likely candidate is the phosphatidylcholine (PC) having an sn-2-short-chain acyl group with a methyl, hydroxyl, aldehydic or carboxylic terminal. These unique PCs, formed by oxidative fragmentation of the polyunsaturated acyl group of the parent PC in liposomes, low density lipoproteins and blood plasma, induce platelet aggregation through the activation of the receptor for platelet-activating factor (PAF), due to their resemblance in structure with PAF. We have found that PAF-like lipids regulate DNA synthesis and production of nitric oxide independently of the activation of the PAF receptor in vascular smooth muscle cells. Regulation of vascular cell function through two distinct signaling pathways mediated by PAF-like lipids provides new insight into the mechanism of induction of atherosclerosis.

en: BioFactors

ja: BioFactors