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。     

靶向载药系统毫微粒及其应用

近年来发展了一系列新的载药系统如脂质体和纳米级大小的固态颗粒系统。后者被称作毫微粒(nanoparticles)。毫微粒用于运载药物,可以降低循环系统中游离药物或蛋白结合药物的量;减少用药量;可以使药物在某些     

载药纳米微粒的研究进展

载药纳米微粒是纳米技术与现代医药学结合的产物,是一种新型的药物和基因输送载体。它具有缓释药物、透过生物屏障靶向输送药物、将 DNA导入细胞浆质内和建立新的给药途径等优势。     

磁性微粒靶向给药系统治疗消化道恶性肿瘤的基础研究与临床初探

OBJECTIVE Study the therapeutic effect on digestive canal cancers with magnetic Microne Target.METHODS 1.Basic study acute toxicity test,chronic toxicity test,pharmacodynamic experiment.2.Clinical study magnetic microne gum-solution was detained in the di     

磁性微粒靶向给药系统治疗消化道恶性肿瘤的基础研究与临床初探

目的研究磁性微粒靶向给药系统对消化道恶性肿瘤的治疗作用。方法基础研究以大鼠和小鼠为实验对象进行急性毒性试验、慢性毒性试验、药效学实验;临床研究以消化道恶性肿瘤患者为研究对象,在病灶局部注射磁性抗癌药,外加体表相应部位磁场的作用,使磁性微粒胶液滞留于局部,缓慢释放抗癌药,杀死瘤体癌细胞,达到治疗作用。结果基础研究显示:磁性微粒靶向给药系统不良反应小,有抗肿瘤的作用。临床研究显示:肿瘤部位明显缩小,该方法可杀死局部瘤细胞,而对其他组织和脏器不良反应小,该给药方法有选择性。结论该疗法可单独应用,有一定的推广价值。     

肿瘤靶向纳米载药系统的设计与构建

近年来将纳米载药系统应用于肿瘤靶向递药的研究层出不穷。与正常组织相比,肿瘤组织具有较低的p H环境、大量新生血管生成、不规则的血流灌注、局部缺氧等特异性的微环境,利用这些特点进行合理的纳米载药系统设计能够实现肿瘤部位的高效递药及深层穿透,显著提高肿瘤治疗效果。针对现有的肿瘤靶向纳米载药系统的构建与设计方法进行综述,以阐述纳米载药系统在肿瘤靶向传递中的研究进展。     

磁性靶向载药微球研究进展

磁性靶向药物治疗具有疗效高、用药量少、不良反应小等特点,是近年来发展的一种新的治疗肿瘤的方法。该文主要介绍了靶向给药治疗的机制及磁性靶向载药微球的构成和研究进展,并对其发展前景进行了展望。     

纳米微粒靶向治疗脑癌研究进展

抗肿瘤药物的发展已进入新时期,纳米技术、新型靶向制剂的研究日趋成熟。由纳米技术与现代药物学结合形成的载药纳米微粒是一种新型的药物输送体系。本文通过检索大量相关文献,对纳米粒和靶向制剂在脑癌中的应用进行分析总结。     

磁性微粒——一种有效的靶向给药系统

目前治疗恶性肿瘤 ,除外科手术外 ,主要使用化学药物、生物毒素及放射性核素等 ,但药物治疗存在选择性低、毒副作用大、抗肿瘤药物很快从作用部位消失等缺陷。高分子包覆磁性微粒用作活体治疗成为一种药物定点释放新技术〔1〕。该技术将抗癌药物包覆或修饰于具有生物可降解性的磁性微粒上 ,并通过一个外加磁场将药物定位于病变部位 ,使化疗或放射性治疗制剂集中于靶 (如肿瘤 )部位附近 ,而对周围其它正常组织无毒副作用。目前人们已经可根据需要定向合成出表面具有亲水性、生物相容性、无毒及无免疫原性的磁性微粒〔2〕并用于癌症治疗中。1…     

靶向性纳米载药系统对中枢神经系统疾病作用的研究进展

目的由于血脑屏障的存在,大多数常规制剂中的药物难以进入脑部,影响脑部疾病的诊疗效果,利用纳米微粒作为载药系统可以使药物穿透血脑屏障。方法将大分子药物制成纳米粒,可增大中枢神经系统中药物浓度及延长药效,增加了对脑内病灶的靶向性。结果与结论尽管纳米给药系统用于脑部疾病靶向的治疗距临床应用仍有相当多的工作尚待完成,但目前的研究已展现其重要的意义。     

Macrophage-evading and tumor-specific apoptosis inducing nanoparticles for targeted cancer therapy

Extended circulation of anticancer nanodrugs in blood stream is essential for their clinical applications. However, administered nanoparticles are rapidly sequestered and cleared by cells of the mononuclear phagocyte system (MPS). In this study, we developed a biomimetic nanosystem that is able to efficiently escape MPS and target tumor tissues. The fabricated nanoparticles (TM-CQ/NPs) were coated with fibroblast cell membrane expressing tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL). Coating with this functionalized membrane reduced the endocytosis of nanoparticles by macrophages, but increased the nanoparticle uptake in tumor cells. Importantly, this membrane coating specifically induced tumor cell apoptosis via the interaction of TRAIL and its cognate death receptors. Meanwhile, the encapsulated chloroquine (CQ) further suppressed the uptake of nanoparticles by macrophages, and synergized with TRAIL to induce tumor cell apoptosis. The vigorous antitumor efficacy in two mice tumor models confirmed our nanosystem was an effective approach to address the MPS challenge for cancer therapy. Together, our TM-CQ/NPs nanosystem provides a feasible approach to precisely target tumor tissues and improve anticancer efficacy.     

整合素阻断剂抗肿瘤药物研究进展

整合素是存在于细胞表面的跨膜糖蛋白受体,能介导细胞间的黏附,参与血管生成和肿瘤转移,与肿瘤的发生发展密切相关。以整合素为靶点进行抗肿瘤治疗,可有效抑制肿瘤的生长和转移。本文主要从抗肿瘤生长类药物、抗肿瘤转移类药物、抗血管生成类药物等方面对近年来整合素阻断剂抗肿瘤药物研究进展进行综述,并对整合素靶向给药的剂量问题进行了讨论。     

功能化纳米粒在脑靶向递药中应用的研究进展

血脑屏障的存在,导致药物不能有效到达靶部位发挥作用,极大的影响神经系统药物的发展和进步。纳米技术已被证明是用于脑靶向治疗的一种有效工具,尤其在脑肿瘤和神经退行性疾病中应用甚广。功能化纳米粒通过表面修饰等提高药物的顺应性,在药物原来的治疗基础上,达到更加精准的靶向性,高效率在靶部位聚集,起到治疗作用。本文主要综述功能化纳米粒及其功能化策略,总结了影响功能化纳米粒脑靶向运输的因素,同时对功能化的纳米粒在脑部疾病治疗中的优势和应用进行阐述,为其相关研究提供参考。     

Multifunctional magnetic nanoparticles for targeted imaging and therapy

Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials.     

Methods for investigation of targeted kinase inhibitor therapy using chemical proteomics and phosphorylation profiling

Phosphorylation acts as a molecular switch for many regulatory events in signaling pathways that drive cell division, proliferation, and apoptosis. Because of the critical nature of these protein post-translational modifications in cancer, drug development programs often focus on inhibitors for kinases and phosphatases, which control protein phosphorylation. Numerous kinase inhibitors have entered clinical use, but prediction of their efficacy and a molecular basis for patient response remain uncertain. Chemical proteomics, the combination of drug affinity chromatography with mass spectrometry, identifies potential target proteins that bind to the drugs. Phosphorylation profiling can complement chemical proteomics by cataloging modifications in the target kinases and their downstream substrates using phosphopeptide enrichment and quantitative mass spectrometry. These experiments shed light on the mechanism of disease development and illuminate candidate biomarkers to guide personalized therapeutic strategies. In this review, commonly applied technologies and workflows are discussed to illustrate the role of proteomics in examining tumor biology and therapeutic intervention using kinase inhibitors.     

Alpha-particles for targeted therapy

Alpha-particles are helium nuclei that deposit DNA damaging energy along their track that is 100 to 1000 times greater than that of conventionally used beta-particle emitting radionuclides for targeted therapy; the damage caused by alpha-particles is predominately double-stranded DNA breaks severe enough so as to be almost completely irreparable. This means that a small number of tracks through a cell nucleus can sterilize a cell and that, because the damage is largely irreparable, alpha-particle radiation is not susceptible to resistance as seen with external radiotherapy (e.g., in hypoxic tissue). The ability of a single track to influence biological outcome and the stochastic nature of alpha-particle decay require statistical or microdosimetric techniques to properly reflect likely biological outcome when the biologically relevant target is small or when a low number of radionuclide decays have occurred. In therapeutic implementations, microdosimetry is typically not required and the average absorbed dose over a target volume is typically calculated. Animal and cell culture studies have shown that, per unit absorbed dose, the acute biological effects of alpha-particles are 3 to 7 times greater than the damage caused by external beam or beta-particle radiation. Over the past ten to 15 years, alpha-particle emitting radionuclides have been investigated as a possible new class of radionuclides for targeted therapy. Results from the small number of clinical trials reported to date have shown efficacy without significant toxicity.     

PH-responsive strontium nanoparticles for targeted gene therapy against mammary carcinoma cells

Genetic intervention via the delivery of functional genes such as plasmid DNA (pDNA) and short-interfering RNA (siRNA) offers a great way to treat many single or multiple genetic defects effectively, including mammary carcinoma. Delivery of naked therapeutic genes or siRNAs is, however, short-lived due to biological clearance by scavenging nucleases and circulating monocytes. Low cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing activity. Development of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid delivery. Inorganic nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation activity. Here we introduce strontium salt-based nanoparticles, namely, strontium sulfate, strontium sulfite and strontium fluoride as new inorganic nanocarriers. Generated strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and siRNA. Degradation of the particles was seen with a drop in pH, suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic materials. While the particles are relatively nontoxic towards the cells, siRNA-loaded SrF₂ and SrSO₃ particles exerted superior transgene expression and knockdown activity of MAPK and AKT, leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 cells. Strontium salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.     

肿瘤生物标志物在肿瘤个性化治疗中的意义

肿瘤严重危害人类健康,肿瘤生物标志物在个性化治疗过程中可用于肿瘤早期筛查,临床分期与肿瘤诊断,判断预后、治疗监测和疗效判断,也可作为治疗预测及肿瘤治疗的靶点,提高治疗针对性从而提高肿瘤治愈率,减少患者不必要的痛苦。本研究主要对肿瘤生物标志物的分类、主要检测方法及其在肿瘤个性化治疗和肿瘤靶向性治疗中的作用进行综述。     

Mannose receptor targeted bioadhesive chitosan nanoparticles of clofazimine for effective therapy of tuberculosis

Drug-resistant tuberculosis (TB) is one of the most lethal diseases, and it is imperative to exploit an advanced drug formulation for its effective treatment. This work aims to develop a mannose receptor-targeted bioadhesive chitosan nanoparticles for effective drug-resistant tuberculosis treatment. The clofazimine loaded chitosan nanoparticles were formulated; their size, charge, polydispersity (PDI), surface morphology, entrapment efficiency (EE) and in-vitro release pattern were established. Also, cellular uptake study on C2C12 cell lines and anti-mycobacterial activity against H37Rv (a standard strain of Mycobacterium tuberculosis) were evaluated. The particle sizes of formulated chitosan nanoparticles were in the range of 132–184 nm and EE was also found to be between 73 and 95%. The functionalization of bioadhesive chitosan nanoparticles with mannose was confirmed by infrared spectroscopy (FTIR). The uptake studies on the C2C12 cell lines showed that mannosylated nanoparticles were more efficiently internalized when compared to non-targeted nanoparticles. Further, luciferase reporter phage (LRP) assay against H37Rv strain showed that clofazimine nanoparticles were found to be 49.5 times superior in terms of inhibition and anti-mycobacterial activity than free clofazimine. This excellent activity might be attributed to enhanced drug delivery with a promising bioadhesion property of chitosan-based nanoparticles.     

Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles

The lack of information related to the scaling-up of technologies used for preparing polymeric nanoparticles (NP) might hinder the introduction of these colloidal carriers into the pharmaceutical market. In the present study, the scale-up of ibuprofen-loaded NP produced by three manufacturing processes – salting-out, emulsification–diffusion and nanoprecipitation – was assessed at pilot-scale by increasing 20-fold the laboratory-batch volume from 60 ml to 1.5 l. Eudragit^® L100-55 and poly(vinyl alcohol) (PVAL) were used as polymer and emulsifying agent, respectively. The influence of the hydrodynamic conditions on the NP characteristics such as mean size, drug content, residual PVAL and morphology was also investigated. At pilot-scale, stirring rates of 790–2000 rpm lead to NP mean sizes ranging from 557 to 174 nm for salting-out and from 562 to 230 nm for emulsification–diffusion. An increase in the stirring rate enhances the droplet break-up phenomenon which leads to the formation of finer emulsion droplets and thus smaller NP. Moreover, the influence of the stirring rate on the mean size of NP can be predicted using a model based on a simple power law. The continuous method used for nanoprecipitation scale-up allows production of NP in a reproducible way over a relatively short time. Finally, for the three methods, NP characteristics were reproduced well at both scales. However, the scale-up process induced a slight reduction in the size and drug loading of NP.