Innovative Technologies in Nanomedicines: From Passive Targeting to Active Targeting/From Controlled Pharmacokinetics to Controlled Intracellular Pharmacokinetics

Sato, Yusuke; Sakurai, Yasuhisa; Kajimoto, Kazuaki; Nakamura, Takashi; Yamada, Yuma; Akita, Hidetaka; Harashima, Hideyoshi

doi:10.1002/mabi.201600179

Cited by 26 publications

(13 citation statements)

References 120 publications

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“…The endothelial cells lining all the blood vessels in the body are in direct contact with the blood in the circulatory system. Unlike the capillary endothelium in the liver and spleen, which contains relatively large pores or fenestrae, the endothelium in most organs of the body is continuous, with no large pores or fenestrae 18) (Fig. 4).…”

Section: Lnps For Gene Delivery To Endothelial Cellsmentioning

confidence: 99%

“…Generally, systemically administered LNPs carrying nucleic acids can access organs in which the capillaries are characterized by the presence of pores or fenestrations such as the liver and spleen. [17][18][19] Parenchymal cells in these two organs are thus considered accessible to LNPs, which make them particularly interesting candidate organs for gene therapy. The liver has received the most attention so far, and several lipid formulations are in different clinical trial stages.…”

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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The last few years have witnessed a great advance in the development of nonviral systems for in vivo targeted delivery of nucleic acids. Lipid nanoparticles (LNPs) are the most promising carriers for producing clinically approved products in the future. Compared with other systems used for nonviral gene delivery, LNPs provide several advantages including higher stability, low toxicity, and greater efficiency. Additionally, systems based on LNPs can be modified with ligands and devices for controlled biodistribution and internalization into specific cells. Efforts are ongoing to improve the efficiency of lipid-based gene vectors. These efforts depend on the appropriate design of nanocarriers as well as the development of new lipids with improved gene delivery ability. Several ionizable lipids have recently been developed and have shown dramatically improved efficiency. However, enhancing the ability of nanocarriers to target specific cells in the body remains the most difficult challenge. Systemically administered LNPs can access organs in which the capillaries are characterized by the presence of fenestrations, such as the liver and spleen. The liver has received the most attention to date, although targeted delivery to the spleen has recently emerged as a promising tool for modulating the immune system. In this review, we discuss recent advances in the use of LNPs for cellspecific targeted delivery of nucleic acids. We focus mainly on targeting liver hepatocytes and spleen immune cells as excellent targets for gene therapy. We also discuss the potential of endothelial cells as an alternate approach for targeting organs with a continuous endothelium.

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Section: Lnps For Gene Delivery To Endothelial Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Khalil

Younis

Kimura

et al. 2020

Biological & Pharmaceutical Bulletin

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“…Polymeric nanoparticles are another drug loading system for BBB penetration improvement. It represented as a solid colloidal system is composed of biocompatible one or more different polymers that have low solubility in water [ 83 , 84 , 85 ]. The specific classification is shown in Figure 7 .…”

Section: Research Progress In Methods For Blood–brain Barrier Permmentioning

confidence: 99%

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

Liu

Liang

et al. 2018

Cells

238

129

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The blood–brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability.

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“…We have continued our research on the development of nanomedicines based on MITO-Porter technology. This research includes fields such as mitochondrial gene therapy [45][46][47], cancer therapy [48][49][50][51][52], ischemic diseases therapy [42,53], and cell therapy [54].…”

Section: Mitochondrial Dds Technologymentioning

confidence: 99%

Challenges in Promoting Mitochondrial Transplantation Therapy

Yamada

Ito

Arai

et al. 2020

IJMS

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Mitochondrial transplantation therapy is an innovative strategy for the treatment of mitochondrial dysfunction. The approach has been reported to be useful in the treatment of cardiac ischemic reperfusion injuries in human clinical trials and has also been shown to be useful in animal studies as a method for treating mitochondrial dysfunction in various tissues, including the heart, liver, lungs, and brain. On the other hand, there is no methodology for using preserved mitochondria. Research into the pharmaceutical formulation of mitochondria to promote mitochondrial transplantation therapy as the next step in treating many patients is urgently needed. In this review, we overview previous studies on the therapeutic effects of mitochondrial transplantation. We also discuss studies related to immune responses that occur during mitochondrial transplantation and methods for preserving mitochondria, which are key to their stability as medicines. Finally, we describe research related to mitochondrial targeting drug delivery systems (DDS) and discuss future perspectives of mitochondrial transplantation.

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Innovative Technologies in Nanomedicines: From Passive Targeting to Active Targeting/From Controlled Pharmacokinetics to Controlled Intracellular Pharmacokinetics

Cited by 26 publications

References 120 publications

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Lipid Nanoparticles for Cell-Specific <i>in Vivo</i> Targeted Delivery of Nucleic Acids

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

Challenges in Promoting Mitochondrial Transplantation Therapy

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