Drug Delivery System最新文献

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Lipid nanoparticles for mRNA delivery 用于信使核糖核酸递送的脂质纳米粒子

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.237

Hiroki Tanaka, Y. Sakurai, H. Akita

引用次数: 1

mRNA therapeutics for central nervous system disorders mRNA治疗中枢神经系统疾病

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.247

Yuta Fukushima, K. Itaka

The high efficacy of mRNA COVID-19 vaccine encourages the wider application of mRNA therapeutics. Protein replacement therapy with mRNA therapeutics is a promising alternative DDS approach for administering trophic factor proteins in central nervous system disorders or enzyme replacement therapy in inherited enzyme deficient diseases. Although the concept to deliver the mRNA in vivo as a drug was demonstrated as early as 1990, mRNA instability hindered subsequent research development. The polymer-based carrier, polyplex nanomicelle, is a novel carrier for in vivo mRNA administration. Here, we introduce the researches of in vivo mRNA administration using the nanomicelle carrier to treat animal models, especially focusing on the central nervous system disorders including Alzheimer’s disease, spinal cord injury and ischemic brain disease. We discuss the advantages of mRNA therapeutics and the characteristics of diseases which are highly suitable for mRNA therapeutics. © 2022, Japan Society of Drug Delivery System. All rights reserved.

mRNA新冠肺炎疫苗的高效性鼓励了mRNA疗法的更广泛应用。mRNA疗法的蛋白质替代疗法是一种很有前途的替代DDS方法，用于在中枢神经系统疾病中给予营养因子蛋白或在遗传性酶缺乏疾病中给予酶替代疗法。尽管早在1990年就已经证明了将信使核糖核酸作为药物在体内递送的概念，但信使核糖核酸的不稳定性阻碍了随后的研究发展。基于聚合物的载体，多聚体纳米胶束，是一种用于体内信使核糖核酸给药的新型载体。在这里，我们介绍了使用纳米胶束载体在体内给予信使核糖核酸治疗动物模型的研究，特别是关注中枢神经系统疾病，包括阿尔茨海默病、脊髓损伤和缺血性脑疾病。我们讨论了信使核糖核酸疗法的优势和高度适合信使核糖核酸治疗的疾病的特点。©2022，日本药物输送系统学会。保留所有权利。

引用次数: 0

Isolation and purification of exosomes 外泌体的分离和纯化

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.264

I. Nakase, Yuki Takahashi

引用次数: 0

Light-responsive RNA delivery 光响应性RNA递送

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.229

Kazunori Watanabe, T. Ohtsuki

引用次数: 0

Cationic polypeptide design for polyion complex-mediated mRNA delivery 阳离子多肽设计用于聚离子复合物介导的信使核糖核酸递送

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.221

Mitsuru Naito, K. Miyata

Recently, with the success of the COVID-19 vaccine, mRNA therapeutics have received a great deal of attention as a next-generation biopharmaceutical. One of the current key issues in mRNA therapeutics is the development of delivery vehicles with higher safety and targetability, excepting the liver. Herein, we introduce a systematic design strategy of cationic polypeptides and their polyplexes for enhanced mRNA delivery. Indeed, a series of cationic polypeptides were synthesized by the aminolysis reaction of poly（β-benzyl-L-aspartate）with varying amine compounds. First, cationic polyaspartamide derivatives were developed for efficient endosomal escape（or endosomal membrane destabilization）by highlighting the acidic pH-sensitivity of aminoethylene（-NHCH2 CH2-）units. Notably, a polyaspartamide derivative（PAsp（DET）） bearing diethylenetriamine（DET）moieties allowed efficient endosomal escape of polyplexes with lowered cytotoxicity. Second, varying hydrophobic moieties were introduced into the side chains of polyaspartamide derivative with the DET moieties to enhance the stability of mRNA-loaded polyplexes. The results indicated that the derivatives with a hydrophobicity index（or logD）＞ –2.4 elicited efficient mRNA transfection in cultured cells. As a result, a polyaspartamide derivative（PAsp（DET/CHE））with DET and cyclohexylethyl（CHE）moieties achieved the most efficient mRNA transfection without marked cytotoxicity, allowing the topical mRNA delivery in the ventricle via intracranial/intrathecal administration and the systemic mRNA delivery into the lung via intravenous administration. Third, self-catalytic degradation of cationic polyaspartamide derivatives was investigated by slightly changing the spacer length in the side chains. The main-chain degradation was substantially affected by the spacer length；the loss of one methylene spacer resulted in the 5-fold higher degradation rate. A polyaspartamide derivative（PAsp（EDA）） bearing the shorter spacer showed higher mRNA transfection efficiency in cultured cells with reduced cytotoxicity with an increase in pre-incubation time, compared with those bearing the longer spacers. Altogether, it is demonstrated that the polyplex-mediated mRNA delivery can be dramatically improved by fine-tuning the chemical structure of cationic polypeptides. © 2022, Japan Society of Drug Delivery System. All rights reserved.

最近，随着新冠病毒疫苗的成功，mRNA治疗剂作为新一代生物制药备受关注。目前mRNA治疗的关键问题之一是开发具有更高安全性和靶向性的递送载体，肝脏除外。在此，我们介绍了一种系统的设计策略，阳离子多肽及其多聚体，以增强mRNA的传递。通过不同胺类化合物对聚β-苄- l-天冬氨酸的氨解反应，合成了一系列阳离子多肽。首先，通过强调氨基(- nhch2 - CH2-)单元的酸性ph敏感性，开发了阳离子聚天冬酰胺衍生物，用于有效的内体逃逸(或内体膜不稳定)。值得注意的是，含有二乙烯三胺(DET)部分的聚天冬酰胺衍生物(PAsp(DET))可以有效地使多聚体内体逃逸，降低细胞毒性。其次，在聚天冬酰胺衍生物的侧链中引入不同的疏水基团与DET基团，以提高mrna负载复合物的稳定性。结果表明，疏水指数(或logD)为> -2.4的衍生物可在培养细胞中高效转染mRNA。结果，聚天冬酰胺衍生物(PAsp(DET/CHE))具有DET和环己基乙基(CHE)部分，实现了最有效的mRNA转染，没有明显的细胞毒性，允许通过颅内/鞘内给药在脑室局部传递mRNA，并通过静脉给药在肺部全身传递mRNA。第三，通过改变侧链上的间隔长度，研究了阳离子聚阿斯巴胺衍生物的自催化降解。主链的降解主要受间隔段长度的影响，每减少一个亚甲基间隔段，降解率提高5倍。与具有较长间隔的细胞相比，具有较短间隔的聚阿斯巴胺衍生物(PAsp(EDA))在培养细胞中表现出更高的mRNA转染效率，并且随着预孵育时间的增加，细胞毒性降低。总之，研究表明，通过微调阳离子多肽的化学结构，可以显著改善多聚体介导的mRNA传递。©2022，日本药物输送系统协会。版权所有。

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引用次数: 0

Think ahead and prepare for future needs 未雨绸缪，为未来的需求做好准备

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.193

Takao Inoue

引用次数: 0

The 37th Annual Meeting of the Academy of Pharmaceutical Science and Technology, Japan 日本医药科学技术学会第37届年会

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.272

Masami Ukawa

引用次数: 0

The current situation and perspectives of mRNA delivery to the kidney 信使核糖核酸肾脏输送的现状与展望

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.253

M. Kawaguchi, Naoya Kato, M. Kamiya, Hidefumi Mukai, Shigeru Kawakami

引用次数: 0

Design of Synthetic mRNAs for Highly Efficient Translation 用于高效翻译的合成信使核糖核酸的设计

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.196

Masahito Inagaki, Mizuki Tada, H. Abe

Recently messenger RNA （mRNA）therapeutics is received much attention as one of the vaccination therapies to compete against the coronavirus disease 2019（COVID-19）pandemic. DDS mRNA therapeutics are generally produced by in vitro transcription utilizing RNA polymerase mediated elongation. However, its purity, stability, and protein synthesis ability, are difficult to be precisely controlled, which is pointed out as drawbacks that must be overcome. To overcome these issues, the introduction of chemically modified nucleic acids is focusing attention. However, it is difficult to flexible molecular design due to the requirement of RNA polymerase recognition ability of chemically modified nucleic acids under in vitro transcription reaction. In the future, the development of a new mRNA design concept based on a flexible molecular design by the progress of chemically modified mRNA therapeutics synthesis method. Under the situation, the authors are focusing on the translation mechanism of mRNA and proposing a new mRNA molecular design to accelerate the translation reaction cycle. In this paper, we introduce an update on therapeutic mRNA design. © 2022, Japan Society of Drug Delivery System. All rights reserved.

最近，信使RNA（mRNA）疗法作为对抗2019冠状病毒病（新冠肺炎）大流行的疫苗接种疗法之一受到了广泛关注。DDSMRNA治疗剂通常通过利用RNA聚合酶介导的延伸的体外转录产生。然而，它的纯度、稳定性和蛋白质合成能力很难精确控制，这被指出是必须克服的缺点。为了克服这些问题，化学修饰核酸的引入引起了人们的关注。然而，由于化学修饰核酸在体外转录反应下对RNA聚合酶的识别能力的要求，很难进行灵活的分子设计。未来，通过化学修饰信使核糖核酸疗法合成方法的进展，开发出一种基于柔性分子设计的新信使核糖核酸设计概念。在这种情况下，作者专注于信使核糖核酸的翻译机制，并提出了一种新的信使核糖核酸分子设计来加速翻译反应周期。在本文中，我们介绍了治疗性信使核糖核酸设计的最新进展。©2022，日本药物输送系统学会。保留所有权利。

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引用次数: 0

For developing next generation of mRNA medicines and vaccines 用于开发下一代mRNA药物和疫苗

Q4 Pharmacology, Toxicology and Pharmaceutics

Drug Delivery System

Pub Date : 2022-07-25 DOI: 10.2745/dds.37.191

K. Itaka

引用次数: 0

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