drug transport

药物运输
  • 文章类型: Journal Article
    姜黄素,作为抗肿瘤剂,由于其代谢物在癌组织中缺乏有效水平,因此未广泛用于癌症治疗。解决载体的障碍和将药物递送到治疗作用的特定部位,同时减少副作用是优先事项。叶酸受体在恶性细胞中表达高,在正常细胞中表达低。叶酸作为靶向配体可以选择性地靶向癌细胞。因此,这篇叙述性综述旨在概述研究不同类型叶酸修饰的姜黄素作为载体和传递剂的研究及其增强治疗药物疗效的结构特性.使用PubMed进行文献检索,Scopus,WebofScience,和谷歌学者数据库。确定了针对该主题的38项临床前研究。目前的研究结果表明,叶酸修饰的纳米颗粒含有姜黄素作为一种有前途的治疗方法可以有效地改善不同类型的癌症。体外研究显示了更高的细胞摄取和细胞毒性效应,更高的细胞抑制,和抗增殖与较低剂量的姜黄素。体内研究表明,在施用叶酸修饰的含有姜黄素的纳米颗粒后,肿瘤抑制更多,肿瘤体积更小,没有毒性。未来的临床试验需要证实叶酸修饰的姜黄素作为癌症治疗新的药物递送平台的有益效果。
    Curcumin, as an anti-tumor agent, is not widely used in cancer treatment due to the lack of effective levels of its metabolites in cancerous tissue. Addressing the barriers to the carrier and delivery of drugs to the specific sites of therapeutic action while reducing side effects is a priority. Folate receptor expression is high in malignant and low in normal cells. Folate as a targeted ligand could selectively target cancer cells. Thus, this narrative review aimed to provide an overview of the studies that have investigated the different types of folate-modified curcumin as a carrier and deliverer and their structural properties that enhance therapeutic drug efficacy. A literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar databases. Thirty-eight preclinical studies addressing this topic were identified. The findings of the current review have shown that folate-modified nanoparticles containing curcumin as a promising therapeutic approach can be effective in improving different types of cancers. In vitro studies have shown a higher cellular uptake and cytotoxicity effect, higher cell inhibition, and anti-proliferation with a lower dosage of curcumin. In vivo studies have shown more tumor suppression and smaller tumor volume without toxicity after the administration of folate-modified nanoparticles containing curcumin. Future clinical trials are needed to confirm the beneficial effect of folate-modified curcumin as a new drug delivery platform for cancer treatment.
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  • 文章类型: Journal Article
    With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.
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  • 文章类型: Journal Article
    异种转运蛋白在决定药物处置和药代动力学中起重要作用。在过去的几十年中,我们对这些重要蛋白质在人类和临床前动物物种中的作用的理解已大大增加。并对人类医学产生了重要影响;然而,兽医学并没有从对兽医学感兴趣的物种的药物转运蛋白的相同数量的研究中受益。转运体表达的差异导致物种之间药物药代动力学参数的外推困难,缺乏物种特异性转运蛋白分布和功能的知识可能导致药物-药物相互作用和不良反应。马是一种对药物转运和转运蛋白表达知之甚少的物种。这篇小型综述的目的是激发人们对马药物转运蛋白和比较转运蛋白生理学的兴趣。
    Xenobiotic transport proteins play an important role in determining drug disposition and pharmacokinetics. Our understanding of the role of these important proteins in humans and pre-clinical animal species has increased substantially over the past few decades, and has had an important impact on human medicine; however, veterinary medicine has not benefitted from the same quantity of research into drug transporters in species of veterinary interest. Differences in transporter expression cause difficulties in extrapolation of drug pharmacokinetic parameters between species, and lack of knowledge of species-specific transporter distribution and function can lead to drug-drug interactions and adverse effects. Horses are one species in which little is known about drug transport and transporter protein expression. The purpose of this mini-review is to stimulate interest in equine drug transport proteins and comparative transporter physiology.
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  • 文章类型: Journal Article
    渗透是使用临床前体外血脑屏障模型评估最多的参数之一,因为它一直被认为是影响中枢神经系统药物递送的主要因素之一。血脑屏障通透性可以定义为化合物穿过脑内皮细胞屏障的速度,并用于评估屏障的密封性。这是体内脑毛细血管的一个重要特征。此外,它被用来评估大脑药物的渗透。我们回顾了传统上用于评估体外血脑屏障通透性的方法,并总结了体内经常被忽视的方法(例如,血浆蛋白和脑组织结合)或体外(例如,文化插入材料或方法)影响此属性的因素。在进行血脑屏障通透性评估时,这些因素至关重要。特别是当比较从不同模型获得的渗透率数据时,因为模型多样化使研究间比较变得显著复杂。最后,测量跨内皮电阻可用于描述血脑屏障的密封性;然而,在将这些测量值与血脑屏障通透性和细胞旁标记物进行比较时,应考虑几个参数。
    Permeation is one of the most evaluated parameters using preclinical in vitro blood-brain barrier models, as it has long been considered to be one of the major factors influencing central nervous system drug delivery. Blood-brain barrier permeability can be defined as the speed at which a compound crosses the brain endothelial cell barrier and is employed to assess barrier tightness, which is a crucial feature of brain capillaries in vivo. In addition, it is used to assess brain drug penetration. We review traditionally used methods to assess blood-brain barrier permeability in vitro and summarize often neglected in vivo (e.g., plasma protein and brain tissue binding) or in vitro (e.g., culture insert materials or methodology) factors that influence this property. These factors are crucial to consider when performing BBB permeability assessments, and especially when comparing permeability data obtained from different models, since model diversification significantly complicates inter-study comparisons. Finally, measuring transendothelial electrical resistance can be used to describe blood-brain barrier tightness; however, several parameters should be considered while comparing these measurements to the blood-brain barrier permeability to paracellular markers.
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  • 文章类型: Journal Article
    Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has provided drug delivery systems that can potentially revolutionize cancer treatment. Nanocarriers, due to their capacity for targeted drug delivery, can shift the balance of cytotoxicity from healthy to cancerous cells. The field of cancer nanomedicine has made significant progress, but challenges remain that impede its clinical translation. Several biophysical barriers to the transport of nanocarriers to the tumor exist, and a much deeper understanding of nano-bio interactions is necessary to change the status quo. Mathematical modeling has been instrumental in improving our understanding of the physicochemical and physiological underpinnings of nanomaterial behavior in biological systems. Here, we present a comprehensive review of literature on mathematical modeling works that have been and are being employed towards a better understanding of nano-bio interactions for improved tumor delivery efficacy.
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  • 文章类型: Journal Article
    Despite current advances in antiemetic treatments, between 30% to and 60% of oncology patients experience chemotherapy-induced nausea (CIN) and 13% to 33% report chemotherapy-induced vomiting (CIV). Inter-individual differences are observed in the occurrence and severity of chemotherapy-induced nausea and vomiting (CINV). This review summarizes and critiques studies on associations between occurrence and severity of CINV and polymorphisms in serotonin receptor, drug metabolism, and drug transport pathway genes. Sixteen studies evaluated the associations between the occurrence and/or severity of CINV and single nucleotide polymorphisms (SNPs). Across these studies, three SNPs in 5-hydroxytryptamine receptor (5-HT3R) genes, two alleles of the cytochrome P450 family 2 subfamily D member 6 (CYP2D6) gene, and three SNPs in ATP binding cassette subfamily B member 1 (ABCB1) gene were associated with the occurrence and severity of CINV. Given the limited number of polymorphisms evaluated, additional research is warranted to identify new mechanisms to develop more targeted therapies.
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