当归多糖铁复合物在大鼠体内2种不同吸收途径的研究

目的:通过当归多糖铁复合物(APIC)2种不同方式给药来探讨其在大鼠体内以游离铁离子形式吸收与直接以多糖铁复合物分子形式吸收这2种不同吸收途径。方法:分别进行正常大鼠APIC高、中、低剂量组灌胃给药和十二指肠给药实验。以原子吸收法测定各时间点血清铁浓度,用DAS2.0软件求算药动学参数。结果:APIC在大鼠体内的药动学过程均符合二室模型,且在本实验所采用剂量范围AUC随着剂量的增加也相应增大。同等剂量灌胃给药,不加抗坏血酸组AUC比加抗坏血酸组AUC稍大。且APIC能以多糖铁复合物分子形式被十二指肠吸收。结论:APIC既能以游离铁离子形式又能以多糖铁复合物分子形式被十二指肠吸收。     

药物直肠吸收的促进剂

经直肠给药以发挥全身作用的研究自1950年后才广泛进行。1980年以来对难以从直肠吸收的药物,开始了添加吸收促进剂的研究。栓剂在直肠内变软液化后,主药在直肠分泌液中溶解释出。溶解的主药被动转运而被吸收,吸收动态与pH分配假说相一致。非离解型是有效的透过形式,油水分配系数大的非离解型分子容易透过生物膜;但解离型分子吸收很差,达不到治疗目的。在     

基于纳米技术的口腔黏膜给药系统

口腔黏膜给药具有药物吸收迅速、无首过效应、患者依从性好等优点。但药物溶解少、唾液携带药物进入胃肠、黏膜存在生理屏障等因素可能影响药物的黏膜渗透和生物利用度。纳米技术应用于药物口腔黏膜给药,可克服上述不利因素,获得高效吸收效果。本综述阐述了口腔黏膜生理结构及影响药物口腔黏膜吸收的因素,汇总了脂质体、固体脂质纳米粒、纳米结构脂质载体、纳米乳、聚合物纳米粒、聚合物胶束、纳米混悬剂等纳米技术在口腔黏膜给药中的应用及促进药物吸收机制,总结了目前研究存在的主要问题,对纳米口腔黏膜给药系统应用前景进行了展望。     

新型口服给药技术的研发进展

口服是目前临床最常用的给药途径.但是,受限于药物分子本身的理化性质、药代特征以及人体复杂的生理环境,单纯依靠普通的制剂技术往往难以充分发挥药物分子的临床治疗效果.近年来,随着制药领域新技术的发展,运用纳米晶、脂质制剂、过饱和固体分散体等给药技术,可改善难溶性小分子药物的溶解性,提高其口服吸收;采用吸收促进剂、酶抑制剂等...     

脂质体纳米药物制剂的生物分析方法及药代动力学研究进展

脂质体纳米药物制剂是一种被脂双分子层囊泡结构包裹的具有纳米尺度的新型药物制剂。脂质体作为药物递送载体,具备生物相容性良好、在体内可被生物降解以及定位靶向性强等优点。应用脂质体纳米药物递送系统,可在一定程度上改善某些药物在人体内的药代动力学行为及药效,减轻不良反应。脂质体纳米药物进入人体后,会释放游离型药物,因而体内会同时存在负载型脂质体纳米药物和游离型药物。负载型药物是药物的贮库,游离型药物与药物的药效和不良反应有关,因此,脂质体药代动力学研究应该同时关注负载型药物和游离型药物。游离药物、脂质体粒子及其材料的精准分析是脂质体体内定量研究的一个难点。本篇综述介绍了脂质体纳米药物的前处理方法,总结了脂质体纳米药物的生物分析方法及其药代动力学的研究进展,希望能够为脂质体纳米药物制剂的研究开发提供参考。     

纳米药物的研究现况

纳米药物具有特异性、靶向性、定量准确、易吸收等特点。本从纳米药物的口服制剂、自乳化释药系统、中枢神经给药系统、基因治疗等方面，阐述了纳米药物的最新研究动态和发展趋向。     

新发现

正意大利和德国纳米药物可以治疗心脏疾病一组来自意大利和德国的研究团队开发出了一种可吸入性纳米颗粒用于治疗心脏病人。近年来纳米颗粒已经被用于递送多种药物到人体各种组织,大多数都采用口服给药或者是静脉注射给药,但是这些方式都不能有效地将药物输送到心脏。因此研究人员开发出了可吸入式纳米药物,使得它们可以更快到达心脏并被心肌细胞吸收,最终改     

药物纳米结晶的研究进展

简述了药物纳米结晶的特有性质及生产技术,讨论其对细胞吸收和毒性的影响.该剂型可以口服、透皮和静注途径给药.其中,经静注给药后,药物纳米结晶可被巨噬细胞吸收而富集于肝脏,再缓释释放,从而达到降低全身毒性的作用.但器官内药物浓度过高也会引起毒性反应.     

低分子肝素直肠栓剂的研制及药效学研究

目的研制低分子肝素直肠栓剂。方法用热融法制备低分子肝素栓剂 ,以体外溶出试验考察其药物释放规律 ,以家兔血液凝固时间的变化证明药物的体内吸收。结果该栓剂体外药物释放符合Fick′s扩散方程 ,低分子肝素能从直肠部位吸收进入体内。结论直肠给药是低分子肝素的又一给药途径。     

载药纳米微粒的应用及研究进展

目的：对纳米、纳米科反及其在药物研究中的应用进行介绍。方法：通过对国内外文献的总结。概述了载药纳米微粒中的普通载药微粒,控释载药微粒、靶向定位载药微粒、载药磁性微粒等类别,介绍了复乳化法技术、超声乳化法、等电临界法、氧化还原法等制备载药纳米微粒的方法。结果：纳米技术与现代医药学结合的产物-载药纳米微粒具有易吸收、定向性强等优点。结论：载药纳米微粒的研究开发可解决口服易水解药物的给药途径,延长药物的体内半衰期,更精确的靶向定位给药。减少药物不良反应,消除生物屏障对药物作用的影响。     

纳米药物的生物学特点及其机制研究概况

纳米药物的小尺寸、高比表面和高活性赋予纳米给药系统较高的穿透生物膜屏障、组织器官选择性分布和缓控释等许多新的生物活性。该文根据现有的文献报道和本课题组的多年研究结果,对纳米药物吸收、转运和分布等体内过程和机制进行综合性阐述,旨在提高相关研究人员的关注和研究参考。     

On Harvesting and Handling of Porcine Jejunal Mucus: A Few Tricks of the Trade

As a heterogeneous hydrogel, mucus has evolved into a formidable physiological barrier protecting the human body from external pathogens and toxic molecules. With mucin as its primary solid component, the viscoelasticity of mucus remains dynamic and dependent upon a plethora of factors, including pathological state, food intake, and infection. Current nanomedicine research strives toward developing nanoformulations that can permeate through the mucus barrier and release the encapsulated cargo of drug molecules at the vicinity of epithelial lining or be directly absorbed into the bloodstream. However, it is difficult to mimic mucus in vitro while the ex vivo models remain inadequate or incompatible with many established microscopic platforms. The UCD School of Veterinary Medicine has a rich legacy of working with porcine gut mucus as an experimental model, while some interesting and innovative ideas were developed by researchers here to address these challenges. This article presents a snapshot of those ideas and life hacks that the author wishes to share with the nanomedicine research community.     

The big picture on nanomedicine: the state of investigational and approved nanomedicine products

Developments in nanomedicine are expected to provide solutions to many of modern medicine's unsolved problems, so it is no surprise that the literature contains many articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or to take a very forward-looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the many nanomedicine products already in use in humans, this study indentifies several interesting trends forecasting the future of nanomedicine.From the Clinical EditorIn this one of a kind review, the state of nanomedicine commercialization is discussed, concentrating only on nanomedicine-based developments and products that are either in clinical trials or have already been approved for use.     

Squalenoyl nanomedicine of gemcitabine is more potent after oral administration in leukemia-bearing rats: study of mechanisms

In an earlier report, we demonstrated the superior anticancer efficacy of orally administered squalenoyl gemcitabine (SQdFdC) nanomedicine over its parent drug gemcitabine on rats bearing RNK-16 large granular lymphocytic (LGL) leukemia. In the present communication, we investigated the mechanisms behind this observation both at the cell and tissue level. The mechanisms were investigated by performing cytotoxicity, cell uptake, and biodistribution experiments. In the presence of cytidine deaminase, SQdFdC nanoassemblies resisted deamination and exerted significant anticancer activity in vitro against RNK-16 LGL leukemia cells, whereas the cytotoxicity of free gemcitabine decreased by approximately 83-fold, indicating its degradation due to deamination. Additionally, the SQdFdC showed considerably higher intracellular accumulation and retention compared with gemcitabine (P<0.05). Unlike gemcitabine, the cellular access to SQdFdC was not influenced by nucleoside transporters. When administered orally to rats, unlike H-gemcitabine, the H-SQdFdC absorbed slowly, but exhibited an improved pharmacokinetics and tissue distribution profile, particularly in the lymphoid organs (the major organs of metastasis). The resistance to deamination, followed by the improved pharmacokinetic and tissue distribution, and greater accumulation and retention at the level of cancer cells, are the key factors for the superiority of SQdFdC nanoassemblies over free gemcitabine against RNK-16 LGL leukemia in rats.     

纳米药物制剂体内分析方法及药动学研究进展和问题策略分析

近年来随着纳米技术的不断发展,纳米药物制剂在改善药物递送、提高生物利用度方面显示出独特优势,已成为临床新药开发研究的热点,为诸多疾病尤其是恶性肿瘤的治疗提供了新思路。然而,由于对纳米药物制剂的体内过程了解不够全面,导致纳米药物制剂的临床转化率极低,严重制约了纳米药物制剂的发展。基于纳米药物制剂良好的应用前景及目前药动学研究中存在的关键问题,调研了国内外的相关文献,首先介绍了常见的具有不同纳米载体类型的纳米药物制剂的种类,对纳米药物制剂体内药物浓度分析测定的方法进行归纳总结,最后分析纳米载体的理化性质对纳米药物制剂体内药动学行为的影响,旨在为纳米药物制剂的体内过程研究提供参考,以获取更为全面的体内药动学数据,提高药物的临床转化率。同时针对目前纳米药物制剂的载体研究、体内浓度定量分析方法以及药动学研究中存在的问题进行讨论,以期为纳米药物制剂的研究与开发利用提供方向。     

From bench to bedside: successful translational nanomedicine: highlights of the Third Annual Meeting of the American Academy of Nanomedicine

The Third Annual Meeting of the American Academy of Nanomedicine (AANM) was held at the University of California San Diego, in San Diego, California during September 7-8, 2007. The meeting was focused on successful translational nanomedicine: from bench to bedside. There were four keynote lectures and eight scientific symposiums in this meeting. The researchers and investigators reported the results and process of current nanomedicine research and approaches to clinical applications. The meeting provided exciting information for nanomedicine clinical-related researches and strategy for further development of nanomedicine research which will be benefits to clinical practice.     

Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in heterogeneous population of primary acute myeloid leukemia cells including refractory and relapsed cases

Aberrant epigenetics play a key role in the onset and progression of acute myeloid leukemia (AML). Herein we report in silico modelling based development of a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti-leukemic activity against heterogeneous population of AML patient samples (n = 9), including refractory and relapsed cases, and three representative cell lines expressing CD34⁺/CD38⁻ stem cell phenotype (KG-1a), promyelocytic phenotype (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~ 100 nm size exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell lines and patient samples, and induced enhanced HDAC inhibition, oxidative injury, cell cycle arrest and apoptosis compared to free vorinostat. Most importantly, nanomedicine showed exceptional single-agent activity against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. Collectively, this epigenetics targeted nanomedicine appears to be a promising therapeutic strategy against various French-American-British (FAB) classes of AML.From the Clinical EditorThrough the use of a protein-vorinostat agent, exceptional single-agent activity was demonstrated against the clonogenic proliferative capability of bone marrow derived leukemic progenitors, while remaining non-toxic to healthy bone marrow cells. The studied epigenetics targeted nanomedicine approach is a promising therapeutic strategy against various French-American-British classes of acute myeloid leukemia.     

纳米药物递送系统靶向动脉粥样硬化斑块的研究进展

心血管疾病是全球死亡率最高的疾病,而动脉粥样硬化是心血管疾病主要诱因.鉴于常规的给药方式,进入斑块的药物浓度很低,难以实现直接针对斑块的有效治疗策略.纳米药物递送系统在靶向斑块、斑块局部释放药物和提高斑块内药物有效浓度等方面具有显著优势,为动脉粥样硬化的诊断、治疗和疗效评估等提供了切实可行的方法和技术平台.本文从靶向递送策略的角度对近年来针对动脉粥样硬化斑块的纳米药物递送系统进行综述,为纳米药物递送系统应用于动脉粥样硬化诊疗的设计和构建提供参考.     

纳米药物在肝癌靶向治疗中的研究进展

目的了解肝癌靶向治疗的纳米药物种类及不同靶向机制,为纳米药物的进一步研发提供参考。方法对国内外相关文献进行归纳和综述。结果和结论纳米药物在肝癌靶向治疗中有着独特的优势,具有广阔的研究和开发前景。     

Just so stories: The random acts of anti-cancer nanomedicine performance

Contrary to high expectations, the majority of clinically approved anti-cancer nanomedicine, and those under clinical trials, have shown limited therapeutic efficacy in humans. So, why these nanomedicine are not delivering their promise? Here, we discuss likely factors, and call for a paradigm shift in approach and design of future cancer nanotherapeutics based on realistic cancer models representing human disease, and better understanding of integrated pathophysiological processes, including systems immunology, that modulate human tumor functionality and growth.From the Clinical EditorThis critical review of the current state of translational oncology research utilizing nanomedicine-based approaches provides a comprehensive discussion of the multiple factors that are responsible for poor outcomes when translating these approaches models to the actual human disease.