发表一篇学和医学成像类SCI论文
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Abstract:
:Small, synthetic oligonucleotides (ON) are of great interest as potential disease modifying drugs, mainly because of their ability to modulate previously undruggable target mutations. To date, therapeutic applications of ON are, however, limited by their physicochemical properties, including poor stability, rapid excretion and low intracellular access. In order to overcome some of these shortcomings, ON are generally formulated using nanoparticle (NP) delivery systems. Alternatively, the poor stability can be circumvented by including chemical modifications to the backbone or sugars of the ON. Some of these modifications also result in better intracellular target access of these otherwise membrane-impermeable macromolecules. Therefore, complex formulation of ON into NP in order to overcome the hurdle of intracellular access might not always be needed, especially in case of local delivery. In this study, the delivery and functionality of chemically modified ON in free form was compared to polymeric NP assisted delivery, measuring their effectivity and efficiency. For this reason, phosphorothioate (PS) backbone-modified 18-mer ON with either 2'OMe or 2'MOE-modifications were selected, capable of eliciting exon-skipping of an aberrant exon in fluorescence based in vitro and in vivo model systems. The NP consisted of poly(D,L-lactic,co-glycolic acid) and poly-β-amino-ester, previously demonstrated to successfully deliver nucleic acids via the pulmonary route. Several NP formulation parameters were tested in order to optimize the delivery of the ON, including ratio polymer:ON, NP size and concentration. The results reported here show clear differences between gymnotic and nanoparticle mediated ON delivery in terms of cellular uptake and local tissue distribution. In vitro, differences in exon-skipping efficiencies were observed with 2'OMe and 2'MOE ON either in free form or formulated in NP, with the striking observation that 2'OMe ON formulated in polymeric NP did not result in exon skipping. Gymnotic delivery of 2'MOE ON into the respiratory tract of mice resulted in functional delivery of exon-skipping ON into nasal epithelia and lungs as well as other downstream tissues and organs, pointing towards a gradual redistribution of locally delivered ONs, with limited but measurable systemic exposure. Conversely, NP-mediated delivery into the respiratory tract resulted in a more contained functional delivery at 10× lower ON doses compared to gymnotic delivery. Based on these findings we conclude that gymnotic delivery of 2'OMe or 2'MOE exon-skipping ON to the respiratory tract is effective, but that NP formulation might be advantageous in case spread of ON to non-target tissue can lead to undesired effects.
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SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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The journal publishes papers on the science and technology of the controlled release and delivery of drugs and other agents. The terms "controlled release" and "delivery" are used in their broadest sense to include mechanisms such as diffusion, chemical and enzymatic reactions, dissolution, osmosis, targeting, and the utilization and manipulation of biological processes. A broad spectrum of papers dealing with all aspects of controlled release and delivery, including gene delivery, tissue engineering and diagnostic agents, is encouraged. The use of prodrugs and carriers such as water-soluble polymers, micro- and nanoparticles, liposomes and micelles is included in the scope. Relevant papers on the toxicology and biocompatibility of drug delivery systems are also published. In addition to original full length papers, notes, reviews and rapid communications, the journal includes book reviews, reports of future meetings, and announcements pertaining to the activities of the Controlled Release Society.
该杂志发表了关于药物和其他制剂的控释和交付的科学和技术论文。术语“控制释放”和“传递”在广义上包括扩散、化学和酶反应、溶解、渗透、靶向以及生物过程的利用和操作等机制。鼓励发表涉及控释和释放所有方面的广泛论文,包括基因释放、组织工程和诊断试剂。前药和载体的使用,如水溶性聚合物,微和纳米颗粒,脂质体和胶束包括在范围内。还发表了有关药物给药系统毒理学和生物相容性的相关论文。除了原稿、笔记、评论和快速通讯外,该杂志还包括书评、关于未来会议的报告和有关管制发行协会活动的公告。
大类(学科) | 小类(学科) | 学科排名 |
医学 |
PHARMACOLOGY & PHARMACY (药学) 2区 CHEMISTRY, MULTIDISCIPLINARY (化学综合) 1区 |
23/171 9/261 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
479 | 394 | 85 |
引文计数(2018)
文献(2015-2017)
12605次引用
1596篇文献
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Pharmacology, Toxicology and Pharmaceutics
小类(学科):Pharmaceutical Science
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#4/174
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影响因子:5.576
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研究方向:MEDICINE, GENERAL & INTERNAL-
影响因子:11.15
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研究方向:医学-医学:内科
发表一篇学和医学成像类SCI论文
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