Tissue distribution

组织分布
  • 文章类型: Journal Article
    小干扰RNA(siRNA)有望成为各种疾病的治疗方法,然而,在实现有效交付方面仍然存在挑战,生物分布,最小化脱靶效应。正在开发脂质纳米制剂来解决这些障碍,但临床前研究的最佳剂量仍不清楚.本系统综述和荟萃分析旨在确定纳米制剂siRNA的最佳剂量,并探索影响剂量和生物分布的因素。为该领域未来的研究提供信息。对四个电子数据库进行了全面搜索,确定了25项潜在研究,筛选后选择15人进行荟萃分析。质量评估是使用SYRCLE的偏倚风险工具进行的,该工具根据研究问题修改为动物研究。研究发现,平均siRNA剂量为1.513±0.377mg/kg,平均下调为65.79%,siRNA-LNP主要在肝脏中积累。虽然个别因素没有显着相关性,观察到剂量和下调之间的正相关,其他影响因素。将静脉注射剂量外推至潜在的口服剂量,我们建议初始口服剂量范围为1.5至8毫克/千克,考虑siRNA-LNP的生物利用度。这些发现有助于推进RNA干扰研究,并鼓励进一步探索个性化医疗中基于siRNA的治疗方法。
    Small interfering RNA (siRNA) holds promise as a therapeutic approach for various diseases, yet challenges persist in achieving efficient delivery, biodistribution, and minimizing off-target effects. Lipidic nanoformulations are being developed to address these hurdles, but the optimal dose for preclinical investigations remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of nanoformulated siRNA and explore factors influencing dose and biodistribution, informing future research in this field. A comprehensive search across four electronic databases identified 25 potential studies, with 15 selected for meta-analysis after screening. Quality assessment was conducted using SYRCLE\'s risk of bias tool modified for animal studies based on research question. Study found an average siRNA dose of 1.513 ± 0.377 mg/kg with mean downregulation of 65.79 % achieved, with siRNA-LNPs mainly accumulating in the liver. While individual factors showed no significant correlation, a positive association between dose and downregulation was observed, alongside other influencing factors. Extrapolating intravenous doses to potential oral doses, we suggest an initial oral dose range of 1.5 to 8 mg/kg, considering siRNA-LNPs bioavailability. These findings contribute to advancing RNA interference research and encourage further exploration of siRNA-based treatments in personalized medicine.
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  • 文章类型: Journal Article
    纳米技术通过引入有效递送药物的创新方法,显著改变了癌症治疗。这篇文献综述深入分析了纳米载体在癌症治疗中的作用。特别关注隐身效应的关键概念。隐形效应是指纳米载体逃避免疫系统和克服生理障碍的能力。该评论调查了各种纳米载体的设计和组成,如脂质体,胶束,和无机纳米粒子,强调表面改性和功能化的重要性。免疫系统之间复杂的相互作用,调理,吞噬作用,并检查了蛋白质电晕以了解隐形效应。审查仔细评估了增强隐身效果的策略,包括聚合物表面涂层,仿生伪装,和靶向配体。隐形纳米载体的体内行为及其对药代动力学的影响,生物分布,和毒性也进行了系统检查。此外,这篇综述介绍了临床应用,批准的基于纳米载体的癌症治疗的案例研究,和临床试验中的新兴配方。该领域的未来方向和障碍,例如纳米载体工程的进步,个性化纳米医学,监管方面的考虑,和道德含义,进行了详细讨论。该综述总结了主要发现,并强调了隐形纳米载体在彻底改变癌症治疗方面的变革潜力。这篇综述通过提供对先进研究的见解,增强了对基于纳米载体的癌症疗法及其潜在影响的理解。临床应用,和监管方面的考虑。
    Nanotechnology has significantly transformed cancer treatment by introducing innovative methods for delivering drugs effectively. This literature review provided an in-depth analysis of the role of nanocarriers in cancer therapy, with a particular focus on the critical concept of the \'stealth effect.\' The stealth effect refers to the ability of nanocarriers to evade the immune system and overcome physiological barriers. The review investigated the design and composition of various nanocarriers, such as liposomes, micelles, and inorganic nanoparticles, highlighting the importance of surface modifications and functionalization. The complex interaction between the immune system, opsonization, phagocytosis, and the protein corona was examined to understand the stealth effect. The review carefully evaluated strategies to enhance the stealth effect, including surface coating with polymers, biomimetic camouflage, and targeting ligands. The in vivo behavior of stealth nanocarriers and their impact on pharmacokinetics, biodistribution, and toxicity were also systematically examined. Additionally, the review presented clinical applications, case studies of approved nanocarrier-based cancer therapies, and emerging formulations in clinical trials. Future directions and obstacles in the field, such as advancements in nanocarrier engineering, personalized nanomedicine, regulatory considerations, and ethical implications, were discussed in detail. The review concluded by summarizing key findings and emphasizing the transformative potential of stealth nanocarriers in revolutionizing cancer therapy. This review enhanced the comprehension of nanocarrier-based cancer therapies and their potential impact by providing insights into advanced studies, clinical applications, and regulatory considerations.
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  • 文章类型: Journal Article
    介孔二氧化硅纳米粒子(MSNs)由于其独特的介观结构特征(高比表面积,大孔隙体积,和可调的孔隙结构),易于改性的表面,高载药量,和持续释放配置文件。然而,MSN在健康组织中的持久和非特异性富集可能由于其降解缓慢而导致毒性并阻碍其临床应用。可降解MSN的出现为这一问题提供了解决方案。了解调节这些MSN的降解和清除以促进临床试验和扩大其生物学应用的策略至关重要。这里,各种各样的可降解MSN关于物理化学性质和降解掺杂策略的考虑,MSN在体内的生物分布,内部间隙机构,重点介绍了间隙物理参数的调整。最后,概述了这些可降解和可明确的MSN生物安全战略,并展望了所遇到的挑战。
    Mesoporous silica nanoparticles (MSNs) have attracted extensive attention as drug delivery systems because of their unique meso-structural features (high specific surface area, large pore volume, and tunable pore structure), easily modified surface, high drug-loading capacity, and sustained-release profiles. However, the enduring and non-specific enrichment of MSNs in healthy tissues may lead to toxicity due to their slow degradability and hinder their clinical application. The emergence of degradable MSNs provided a solution to this problem. The understanding of strategies to regulate degradation and clearance of these MSNs for promoting clinical trials and expanding their biological applications is essential. Here, a diverse variety of degradable MSNs regarding considerations of physiochemical properties and doping strategies of degradation, the biodistribution of MSNs in vivo, internal clearance mechanism, and adjusting physical parameters of clearance are highlighted. Finally, an overview of these degradable and clearable MSNs strategies for biosafety is provided along with an outlook of the encountered challenges.
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  • 文章类型: Systematic Review
    目的:药物剂量应理想地基于目标部位的药物浓度,which,对于大多数药物来说,对应于组织。生长和发育对药物组织分布的确切影响尚不清楚。本系统综述汇编了有关儿童全身应用药物组织分布的最新知识,目的是确定该人群组织药代动力学(PK)研究的优先事项。
    方法:在MEDLINE和Embase数据库中进行了系统的文献检索。
    结果:确定了42篇相关文章,其中71%的人调查了抗生素,而其他研究的药物类别是抗癌药物,抗真菌药,驱虫药,镇静剂,甲状腺静力学,免疫调节剂,抗心律失常药,和外显子跳跃疗法。大多数研究(83%)采用组织活检作为采样技术。最常检查扁桃体和/或腺样组织(占所有患者的70%)。大多数研究的样本量较小(中位数9,范围1-93),不包括最年轻的年龄类别(新生儿和婴儿),报告质量低。由于来自不同研究化合物的数据不均匀,给药时间表,人口,和目标组织,研究之间比较PK数据的可能性有限.
    结论:生长和发育对药物组织分布的影响仍然是一个知识空白,由于儿童组织PK数据的缺乏,尤其是在年轻的年龄段。由于可以使用安全研究儿童药物组织分布的技术,因此应鼓励该领域的未来研究。
    OBJECTIVE: Drug dosing should ideally be based on the drug concentrations at the target site, which, for most drugs, corresponds to the tissue. The exact influence of growth and development on drug tissue distribution is unclear. This systematic review compiles the current knowledge on the tissue distribution of systemically applied drugs in children, with the aim to identify priorities in tissue pharmacokinetic (PK) research in this population.
    METHODS: A systematic literature search was performed in the MEDLINE and Embase databases.
    RESULTS: Forty-two relevant articles were identified, of which 71% investigated antibiotics, while drug classes from the other studies were anticancer drugs, antifungals, anthelmintics, sedatives, thyreostatics, immunomodulators, antiarrhythmics, and exon skipping therapy. The majority of studies (83%) applied tissue biopsy as the sampling technique. Tonsil and/or adenoid tissue was most frequently examined (70% of all included patients). The majority of studies had a small sample size (median 9, range 1-93), did not include the youngest age categories (neonates and infants), and were of low reporting quality. Due to the heterogeneous data from different study compounds, dosing schedules, populations, and target tissues, the possibility for comparison of PK data between studies was limited.
    CONCLUSIONS: The influence of growth and development on drug tissue distribution continues to be a knowledge gap, due to the paucity of tissue PK data in children, especially in the younger age categories. Future research in this field should be encouraged as techniques to safely investigate drug tissue disposition in children are available.
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  • 文章类型: Journal Article
    微米和纳米塑料(MNPs)由于其独特的环境影响而吸引了越来越多的全球研究关注。解决不断升级的问题。多样的材料,尺寸,和MNPs的形状导致一系列的环境影响。尺寸,MNPs的一个关键特征,影响他们的环境行为,影响迁移等过程,沉降,聚合,和吸附。此外,大小调节MNPs在水生生物中的生物分布和毒性。这篇综述深入研究了塑料尺寸的综合影响,主要关注环境行为和毒性作用。最终,这篇综述强调了MNP规模的生态意义,为今后该领域的研究奠定了基础。
    Micro and nanoplastics (MNPs) have attracted growing global research attention due to their distinct environmental impacts, addressing escalating concerns. The diverse materials, sizes, and shapes of MNPs result in a range of environmental impacts. Size, a crucial characteristic of MNPs, influences their environmental behavior, affecting processes like migration, sedimentation, aggregation, and adsorption. Moreover, size modulates the biodistribution and toxicity of MNPs in aquatic organisms. This review delves into the comprehensive impacts of plastic size, with a primary focus on environmental behavior and toxic effects. Ultimately, this review emphasizes the ecological implications of MNP size, laying a foundation for future research in this field.
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  • 文章类型: Journal Article
    肿瘤由恶性肿瘤细胞组成,被其他非肿瘤细胞元素包围,在微环境或肿瘤基质中。近年来,关于肿瘤微环境重要性的证据并没有停止增长。它在细胞增殖中起着核心作用,组织侵入,血管生成和细胞迁移。范例是新的FAPI放射性药物家族,其显示成纤维细胞活化蛋白(FAP)的密度,该蛋白在活化的癌症相关成纤维细胞(CAF)的细胞膜中过表达,其存在与不良预后有关。此教育文件包括执行PET/CTFAPI的程序,生物分布和迄今为止在肿瘤学中的主要潜在临床应用。
    Neoplasms are composed of malignant tumor cells, which are surrounded by other non-tumor cellular elements, in what has been defined as the microenvironment or tumor stroma. Evidence on the importance of the tumor microenvironment has not stopped growing in recent years. It plays a central role in cell proliferation, tissue invasion, angiogenesis and cell migration. The paradigm is the family of new FAPI radiopharmaceuticals that show the density of the fibroblast activation protein (FAP) which is overexpressed in the cell membrane of activated cancer-associated fibroblasts (CAF), and its presence is related to poor prognosis. This educational document includes the procedure for performing PET/CT FAPI, biodistribution and the main potentially clinical applications in oncology to date.
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  • 文章类型: Systematic Review
    外泌体是细胞分泌的纳米级细胞外囊泡,由含有各种生物活性物质如蛋白质的脂双层膜包裹,脂质,和核酸。通过亲本细胞的遗传修饰产生的工程化外泌体显示出有望作为药物递送载体,它们已经被证明在治疗癌症方面具有巨大的治疗潜力,心血管,神经学,和免疫性疾病,但是缺乏有关优化载药量和评估递送功效的系统知识。这篇综述总结了目前用于改造外泌体和评估其药物递送效果的方法。以及目前评估外泌体载药量和释放动力学的技术,细胞靶向,生物分布,药代动力学,和治疗结果进行严格检查。此外,本文综述了外泌体工程和药物递送在临床转化中的最新应用。本综述中汇编的知识为外泌体作为治疗剂的合理设计和严格评估提供了框架。强大的表征方法和报告标准的不断进步将加速外泌体工程技术的发展,并为临床研究铺平道路。
    Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies.
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  • 文章类型: Journal Article
    钒酸铈纳米颗粒(CeVO4NPs),它们是原钒酸稀土纳米材料家族的成员,由于其多样化的特性和未来的生物医学应用,已经引起了相当大的兴趣。目前的研究,其中全面概述了CeVO4NP的合成和表征技术,强调声化学方法是生产尺寸和形状可调的CeVO4NP的有效和直接的技术。本文研究了CeVO4NPs的毒性和生物相容性,以及它们的抗氧化和催化性能,这使得它们能够改变生物系统的氧化还原状态并降解有机污染物。此外,CeVO4NPs药用应用的最新进展,比如癌症治疗,抗菌活性,生物传感,和药物或基因传递,强调。此外,CeVO4NPs的缺点,比如稳定性,聚合,生物分布,和生物降解,概述,并提出了几种潜在的解决方案。该研究最后提供了在生物医学行业开发和增强CeVO4NPs的数据和建议。
    Cerium vanadate nanoparticles (CeVO4 NPs), which are members of the rare earth orthovanadate nanomaterial family, have generated considerable interest due to their diverse properties and prospective biomedical applications. The current study, which provides a comprehensive overview of the synthesis and characterization techniques for CeVO4 NPs, emphasizes the sonochemical method as an efficient and straightforward technique for producing CeVO4 NPs with tunable size and shape. This paper investigates the toxicity and biocompatibility of CeVO4 NPs, as well as their antioxidant and catalytic properties, which allow them to modify the redox state of biological systems and degrade organic pollutants. In addition, the most recent developments in the medicinal applications of CeVO4 NPs, such as cancer treatment, antibacterial activity, biosensing, and drug or gene delivery, are emphasized. In addition, the disadvantages of CeVO4 NPs, such as stability, aggregation, biodistribution, and biodegradation, are outlined, and several potential solutions are suggested. The research concludes with data and recommendations for developing and enhancing CeVO4 NPs in the biomedical industry.
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  • 文章类型: Journal Article
    人体组织暴露于DechloranePlus(DP)引起了公众的关注,因为它可能对人类构成多种健康威胁。因此,重要的是总结以往关于人体组织中DP的主要研究结果,并为未来的研究提供潜在的指导。在本文中,系统评价了自2009年以来全球不同人群和人体组织中的DP水平。广东省电子垃圾拆解场工人人体组织DP水平,中国(血清中值190ng·g-1lw)和江苏省的DP制造工厂,中国(全血平均857ng·g-1lw)是全球报道的最高水平。在最近的研究中,普通人群组织中的DP水平接近电子废物拆解地点附近居民的水平,这应该引起关注。发现不同人体组织中的DP水平与血液>母乳>脂肪组织的模式呈正相关。DP在不同人体组织中的分布主要是脂质驱动的,也可能受到DP与蛋白质如人血清白蛋白的相互作用的影响。过去的大多数研究仅通过比较商业DP产品和人体组织中DP的组成来确定DP在人体组织中的异构体立体选择性,缺乏机制证据。最近,发现DP异构体对蛋白质的亲和力明显不同,这似乎证实了DP在人体组织中的异构体选择性。我们通过分子对接模拟了DP与人血清白蛋白的结合以及DP与甲状腺激素受体β的结合,发现syn-DP和anti-DP与所选蛋白质的结合行为存在差异。分子对接似乎是未来研究预测和揭示人体组织中DP行为和健康影响机制的可行方法。
    Exposure of human tissues to Dechlorane Plus (DP) has raised public concern because of the multiple health threats it may pose to humans. Therefore, it is important to summarize the main findings of previous studies on DP in human tissues and to provide potential guidance for future studies. In this paper, DP levels in different populations and human tissues worldwide since 2009 were systematically reviewed. DP levels in human tissues of workers in e-waste dismantling sites in Guangdong Province, China (median 190 ng·g-1 lw in serum) and DP manufacturing plants in Jiangsu Province, China (mean 857 ng·g-1 lw in whole-blood) are the highest reported worldwide. DP levels in tissues of the general population in recent studies are close to those of residents near e-waste dismantling sites, which should be of concern. DP levels in different human tissues were found to be positively correlated with a pattern of blood > breast milk > adipose tissue. The distribution of DP in different human tissues is mainly lipid-driven and may also be influenced by the interaction of DP with proteins such as human serum albumin. Most of the past studies determined the isomer stereoselectivity of DP in human tissues only by comparing the composition of DP in commercial DP products and human tissues, which lacks evidence of mechanism. Recently, a significantly different affinity of DP isomers for proteins was found, which seems to confirm the isomer selectivity of DP in human tissues. We simulated the binding of DP to human serum albumin and DP to thyroid hormone receptor β by molecular docking and found differences in the binding behavior of syn-DP and anti-DP to the selected proteins. Molecular docking seems to be a feasible approach for future studies to predict and reveal the mechanisms of DP behavior and health effects in human tissues.
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  • 文章类型: Journal Article
    99m(99mTc)-二膦酸盐是用于骨闪烁显像的最常见的放射性药物。即使在骨组织中的摄取已被广泛探索,在骨闪烁扫描过程中,在软组织恶性肿瘤中可以看到非典型摄取。血管化和内皮通透性的增加代表了示踪剂生物分布的前排参与者,尽管已经确定了其他原因,例如创伤,坏死,转移中钙化的存在,组织的pH值,因此离子浓度的类型。
    本文的目的是总结在癌组织中看到的非典型软组织摄取的技术状态。这项研究是在PubMed上进行的。文献分析表明,钙代谢和离子饱和在骨示踪剂的生物分布中起着关键作用。这种现象在复杂的情况下排名,包括致癌作用和癌症环境方面。我们还报告了我们机构中的两个病例,其中观察到癌症组织中的非典型摄取。
    UNASSIGNED: Technetium-99m (99mTc)-diphosphonates represent the most common radiopharmaceutical used for bone scintigraphy. Even if the uptake in bone tissue has been widely explored, atypical uptake could be seen in soft tissue malignancies during bone scintigraphy. Increased vascularization and endothelium permeability represent front-row players in the biodistribution of the tracer, albeit other causes have been identified such as trauma, necrosis, the presence of calcification in metastasis, the pH of the tissue and consequently the type of ion concentration.
    UNASSIGNED: The aim of this paper is to summarize the state of art of atypical soft tissue uptake seen in cancer tissues. The research was conducted on PubMed. The analysis of the literature suggests that calcium metabolism and ionic saturation have a pivotal role in the biodistribution of bone tracers. This phenomenon ranks in a complex scenario that includes carcinogenesis and cancer environment aspects. We also report two cases in our Institution in which atypical uptake in cancer tissues was observed.
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