Mitochondrial drug delivery and mitochondrial disease therapy--an approach to liposome-based delivery targeted to mitochondria.
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概要
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Recent progress in genetics and molecular biology has provided useful information regarding the molecular mechanisms associated with the mitochondrial diseases. Genetic approaches were initiated in the late 1980s to clarify the gene responsible for various mitochondrial diseases, and information concerning genetic mutations is currently used in the diagnosis of mitochondrial diseases. Moreover, it was also revealed that mitochondria play a central role in apoptosis, or programmed cell death, which is closely related to the loss of physiological functions of tissues. Therefore, drug therapies targeted to the mitochondria would be highly desirable. In spite of the huge amount of mechanism-based studies of mitochondrial diseases, effective therapies have not yet been established mainly because of the lack of an adequate delivery system. To date, numerous investigators have attempted to establish a mitochondrial drug delivery system. However, many problems remain to be overcome before a clinical application can be achieved. To fulfill a drug delivery targeted to mitochondria, we first need to establish a method to encapsulate various drugs, proteins, peptides, and genes into a drug carrier depending on their physical characteristics. Second, we need to target it to a specific cell. Finally, multi-processes of intracellular trafficking should be sophisticatedly regulated so as to release a drug carrier from the endosome to the cytosol, and thereafter to deliver to the mitochondria. In this review, we describe the current state of the development of mitochondrial drug delivery systems, and discuss the advantage and disadvantage of each system. Our current efforts to develop an efficient method for the packaging of macromolecules and regulating intracellular trafficking are also summarized. Furthermore, novel concept of "Regulation of intramitochondrial trafficking" is proposed herein as a future challenge to the development of a mitochondrial drug delivery system.
- Elsevierの論文
著者
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Kamiya Hiroyuki
Faculty of Pharmaceutical Sciences, Hokkaido University
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Kiwada Hiroshi
徳島大学 ヘルスバイオサイエンス研究部薬物動態制御学
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Kiwada Hiroshi
Faculty Of Pharmaceutifal Sciences The University Of Tokushima
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原島 秀吉
北大院・薬学研究科
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Kamada Haruhiko
医薬基盤研究所 創薬プロテオミクスプロジェクト
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Kiwada Hiroshi
Department Of Pharmacokinetics And Biopharmaceutics Faculty Of Pharmaceutical Sciences The Universit
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Yamada Yuma
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Yamada Yuma
Laboratory For Molecular Design Of Pharmaceutics Faculty Of Pharmaceutical Sciences Hokkaido Univers
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Kamiya Hiroyuki
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Kogure Kentaro
Dep. Of Biophysical Chemistry Kyoto Pharmaceutical Univ.
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Akita Hidetaka
Lab. For Molecular Design Of Pharmaceutics Fac. Of Pharmaceutical Sciences Hokkaido Univ.
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Shim Chang
Faculty Of Pharmaceutical Sciences University Of Tokyo : (present Address) College Of Pharmacy Seoul
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Kasai Hiroshi
Inst. Of Industrial Ecological Sciences Univ. Of Occupational And Environmental Health 1-1 Iseigaoka
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Harashima Hideyoshi
Department Of Pharmacokinetics And Pharmaceutics Graduate School Of Pharmaceutical Sciences The Univ
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Kamiya Hiroyuki
産業医科大学産業生態科学研究所
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Akita Hidetaka
Graduate School Of Pharmaceutical Sciences Hokkaido University
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Kamiya Hiroyuki
Faculty Of Pharmaceutical Sciences Hokkaido University:crest Japan Science And Technology
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山田 勇磨
北海道大学大学院薬学研究科薬剤分子設計学分野
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Kogure Kentaro
Kyoto Pharmaceutical University
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