以适体作为药物“靶向载体”的研究进展

<正>药物的靶向给药已成为近年来药物输送系统领域研究的热点。药物的靶向可分为被动靶向和主动靶向,被动靶向是指依靠药物自身的设计或所制备的药物载体的粒径、形状等因素减少与非靶细胞、组织及器官的非特异性相互作用来     

高分子纳米粒子在靶向药物载体中的研究进展

高分子纳米粒子作为靶向药物的载体材料可将药物选择性地靶向病变部位 ,可以有效降低其对正常组织的毒副作用 ,提高药物的生物利用度 ,是一种新型的药物控释体系。本文综述了高分子纳米粒子在主动靶向药物、被动靶向药物、物理靶向药物载体中的应用     

特异性骨靶向纳米递药系统的优势与临床可应用性

文题释义： 药物靶向性：靶向药物是在目标器官或组织局部形成相对高的浓药物度,减少对非目标器官、组织、细胞的伤害。目前根据靶向目标不同,可分为组织器官水平、细胞水平及亚细胞水平几个层次。根据靶向机制的不同,药物靶向可分为被动靶向、主动靶向、物理靶向等几类,其中的主动靶向即特异性靶向。 纳米药物递送系统：药物递送系统是利用临床医学、药学及材料科学等多学科手段,在恰当的时机将适量的药物递送到正确的位置,从而增加药物的利用效率,提高疗效,降低成本,减少毒副作用。纳米级药物递送系统是指在药剂学中把纳米载体负载治疗药物形成粒径1-1 000 nm纳米粒。因为其纳米级粒径可以使得药物在体内穿过某些生物屏障如血-脑屏障、血-骨髓屏障等,以及利用肿瘤组织的高渗透长滞留效应而达到被动靶向的效果,但其缺乏特异性。背景：在骨相关疾病治疗中特异性主动靶向递药系统非常重要,而纳米技术的发展为其提供了良好的平台,同时为其提供了新的研究思路。 目的：针对以特异性骨靶向递药系统的目前发展及未来前景做一综述。 方法：应用计算机在PubMed、Web of Science和Medline等数据库检索涉及主动骨靶向性递药系统与纳米级递药系统的相关研究,检索关键词为“Bone target therapy,Nanoparticles,Drug delivery system”,检索时间为2014年3月至2019年3月。 结果与结论：靶向基团是特异性骨靶向递药系统的重要组成部分,它决定了递药系统的靶向效率。到目前为止已发现针对于骨组织、破骨细胞、成骨细胞、骨髓间充质干细胞的靶向分子,它们有各自优缺点。目前特异性骨靶向纳米递药系统已在各种骨病领域得到了广泛研究,如转移骨质疏松症、骨髓炎、多发性骨髓瘤、骨肉瘤、骨转移癌等。纳米载体应用的优势为其带来了临床潜力的同时也存在许多挑战,尽管许多基础研究显示出很好的体内结果,但很少有骨靶向基团修饰的纳米递药系统成功地将其转化为临床。 ORCID: 0000-0001-8512-0447(向海滨) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

靶向抗肿瘤纳米药物研究进展

肿瘤是当今严重威胁人类健康的三大疾病之一。然而目前在临床肿瘤治疗和诊断中广泛应用的药物还多数为非选择性药物，体内分布广泛，尤其在一些正常组织和器官中也常有较多分布，常规治疗剂量即可对正常组织器官产生显著的毒副作用，导致患者不能耐受，降低药物疗效，所以提高药物的肿瘤选择性，减少其在非靶向部位的聚集是提高抗肿瘤药物疗效的关键。减少药物对非靶向部位的毒副作用，降低药物治疗剂量并减少给药次数，从而提高药物疗效，这种治疗方法即被称为肿瘤靶向治疗。现今在肿瘤靶向治疗领域，靶向抗肿瘤纳米药物研究正日益受到人们的普遍关注和重视，现就其近年来的研究进展综述如下。     

抗肿瘤药物的靶向给药系统研究进展

目前，临床常用的抗肿瘤药物有70种左右，已进入临床试验的抗肿瘤新药就有四百多种，大多数药物由于特异性较差，常规治疗剂量即可对正常组织器官产生显著的毒副作用而导致患者不能耐受。肿瘤靶向治疗是利用具有一定特异性的载体，将药物或其他杀伤肿瘤细胞的活性物质定向作用于肿瘤组织，而不影响正常组织细胞功能，从而提高疗效、减少毒副作用的一种方法。靶向制剂最初意指狭义的抗癌剂，现今则是指一种采用新技术、     

转铁蛋白在肿瘤和脑主动靶向治疗中应用的研究进展

转铁蛋白可经聚合物、脂质体等与抗肿瘤药物结合,通过转铁蛋白-转铁蛋白受体特异结合途径,可不同程度延长药物血浆半衰期,降低药物的毒副作用,提高药物在肿瘤组织的蓄积量,从而提高药物的主动靶向活性。因此,转铁蛋白可作为一种新型的药物主动靶向载体,在肿瘤靶向治疗中有广阔的应用前景。     

主动靶向载药脂质体在肿瘤治疗中的研究进展

脂质体是理想的药物载体,具有生物相容性好、无免疫原性、表面易功能化等众多优点,并已在肿瘤等疾病的临床治疗中得到应用。对于肿瘤治疗来说,脂质体本身虽然具有一定的被动靶向能力,但单一的被动靶向对提高药物在肿瘤组织的富集率的作用非常有限,主动靶向是提高药物富集率的有效措施。因此几十年来,主动靶向脂质体药物载体获得广泛研究。本文综述了基于载体与肿瘤细胞表面特异性结合的主动靶向脂质体药物载体的研究进展,并总结了该领域存在的机遇、挑战和未来前景。     

静磁场靶向药物递送系统在肿瘤诊疗中的研究进展

化疗是治疗肿瘤的传统手段之一,但其具有组织非特异性,在抑制肿瘤细胞生长的同时也会对正常细胞产生毒副作用.磁靶向药物递送系统可通过具有生物相容性的、稳定的磁性纳米颗粒载体将抗癌药物在外磁场的引导下,靶向运输和浓聚在肿瘤组织.该技术不仅提高了药物运输的效率和药物的抗癌活性,还能降低药物用量和减轻毒副作用.载药磁性纳米颗粒和所应用的外磁场的性质是影响磁性纳米颗粒靶向肿瘤组织的重要影响因素.载药磁性纳米颗粒的靶向递送是否有效,主要依赖靶向目标位置处所应用的磁场和磁场强度是否足够吸引束缚载药磁性纳米颗粒在肿瘤组织中停留以及释放.对静磁场在引导磁性纳米颗粒靶向肿瘤组织研究的新进展进行综述,为静磁场在靶向肿瘤治疗方面提供一定的科研基础支持.     

肺部缓释微球治疗肺部疾病的性能及评价

背景：肺部因其特殊的生理结构而适合作为局部或全身用药的给药部位,而肺部缓释微球在肺部局部疾病治疗乃至全身疾病治疗方面的优越性尚缺乏更多的报道。 目的：评价肺部缓释微球载体材料的释药性能以及临床给药途径的安全性,对比肺部缓释微球与其他肺部给药剂型的差异。 方法：观察微球在肺部的分布及降解情况、肺组织的病理变化和连续给药对肺功能的影响。 结果与结论：肺部缓释微球常用的材料有淀粉、聚乳酸等,具有生物可降解性、生物相容性和生物黏附性,并且缓释微球制备简单,对正常组织无损伤,安全性高,肺部缓释微球在体内有良好的肺靶向性,可提高药物的疗效,降低药物毒副作用,对肺组织无病理性损伤。     

药物缓释载体材料类型及其临床应用

目的:文章对目前国内外几种重要载体材料的临床应用情况进行了阐述。方法:作者以"药物载体,缓释材料,生物降解"为检索词,在中国期刊全文数据通据库(CNKI:1989/2010),采用电子检索的方式对所有相关文献进行了详细检索。排除Meta分析及重复性研究,最终入选20篇文献进入结果分析。结果:生物降解性合成高分子材料安全、可靠,有良好的生物相容性,成为药物缓释载体的首选材料;壳聚糖作为药物缓释载体在减少给药次数,降低药物毒副作用,提高药物疗效等方面具有重要作用;纳米纤维载体可明显增强药物缓释效果;纤维蛋白生物相容性好,是良好的药物缓释载体。结论:药物控制释放体系在机体内可以显示出被动靶向以及缓释等多种优点,它是药物缓释体系的重要组成部分,也是影响药效的主要因素。     

纳米控释抗癌药物研究进展

与普通抗癌药物相比，纳米控释抗癌药物具有可靶向输送、缓释药物、延长给药时间和减少毒副作用等优点，因而具有广阔的应用前景。本文针对目前国内外正在研究并取得一定进展的纳米控释抗癌药物，进行了较全面客观的综述。     

脂质体携载抗HIV-1药物

由于HIV耐药株的产生、特殊器官和细胞中HIV的隐匿、抗HIV药物的毒副反应及半衰期短等问题的出现,促使人们寻找高效低毒和具有靶向性的抗HIV药物.脂质体具有被动或主动靶向病毒复制活跃和贮存区、细胞内靶向和控制药物释放、延长药物半衰期、提高药效和降低毒副作用等优点,是潜在携载抗HIV药物的良好载体.     

Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy

Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity and poor bioavailability of antineoplastic drugs. Nanomedicine plays a pivotal role by delivering drugs in a targeted manner to the malignant tumor cells thereby reducing the systemic toxicity of the anticancer drugs. The objective of this study was to prepare and characterize rapamycin loaded polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) that were surface conjugated with antibodies to epidermal growth factor receptor (EGFR), highly expressed on breast cancer cells, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) mediated cross linking agents. To potentiate the anticancer efficiency of the formulations, in vitro cytotoxicity of native rapamycin, rapamycin loaded nanoparticles and EGFR antibody conjugated rapamycin loaded nanoparticles (EGFR-Rapa-NPs) were evaluated on malignant MCF 7 breast cancer cell lines. IC₅₀ doses as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay showed the superior antiproliferative activity of EGFR-Rapa-NPs over unconjugated nanoparticles and native rapamycin due to higher cellular uptake on malignant breast cancer cells. Cell cycle arrest and cellular apoptosis induced by the above formulations were confirmed by flow cytometry. Molecular basis of apoptosis studied by western blotting revealed the involvement of a cytoplasmic protein in activating the programmed cell death pathway. Thus it was concluded that EGFR-Rapa-NPs provide an efficient and targeted delivery of anticancer drugs, presenting a promising active targeting carrier for tumor selective therapeutic treatment in near future.     

药物控释载体材料的研究与应用

背景：作为控制释放体系的药物载体材料大多是高分子材料,但部分纳米无机材料也正逐步应用到药物控释材料体系中并取得了很好的研究成果。因此,药物控释用载体材料的设计与研究应用越来越受到重视。 目的：对国内外药物控释载体材料的应用及最新研究进展作一综述。 方法：应用计算机检索CNKI和Elsevier SD数据库中1999-01/2011-01关于药物控缓释材料的文章,在标题和摘要中以“高分子,介孔材料,无机硅,磷酸盐,控释”或“polymer,mesoporous materials,Inorganic silicon ,calcium phosphate,controlled release”为检索词进行检索。选择文章内容与药物控缓释有关者,同一领域文献则选择近期发表或发表在权威杂志文章。纳入25篇文献进行综述。 结果与结论：药物控缓释载体材料以用药量小、作用时间长、靶向作用好等特点被广泛关注,但是仍存在载药后药物失活,丧失生物活性等缺陷,目前随着复合药物载体材料和经皮给药装置研究的发展,控缓释材料在临床治疗中的应用必将更加广泛。     

Synthesis and characterization of cisplatin-loaded, EGFR-targeted biopolymer and in vitro evaluation for targeted delivery

The design of smart targeted drug delivery systems that deliver drugs to specific cancer cells will give rise to cancer treatments with better efficacy and lower toxicity levels. We report the development and characterizations of maleimide-functionalized biopolymer (Mal-PGA-Asp) as an effective targeted drug delivery carrier synthesized from an amidation reaction between aspartylated PGA (PGA-Asp) and N-(maleimidohexanoyl)-ethylenediamine (NME). The epidermal growth factor receptor (EGFR) targeting peptide (TP13) was conjugated to Mal-PGA-Asp to obtain the targeting carrier (TP13-Mal-PGA-Asp). Cisplatin was finally loaded by complexation to form a biocompatible and tumor targeted therapeutic drug (TP13-Mal-PGA-Asp3-Pt). The resultant biopolymer with an average size 87 ± 28 nm showed a sustainable release profile with a half-maximal release time (t(1/2) ) of approximately 15 h in physiological saline. Fluorescence imaging and flow cytometry analysis revealed that TP13 significantly enhanced the cellular uptake of TP13-Mal-PGA-Asp3-Pt in the human hepatoma cell line SMMC-7721. The IC(50) value demonstrated the superior anticancer activity of TP13-Mal-PGA-Asp3-Pt over PGA-Asp-Pt. Therefore, the newly developed drug carrier (TP13-Mal-PGA-Asp) obtained in this study may provide an efficient and targeted delivery of anticancer drugs, presenting a promising targeted chemotherapy in EGFR-positive cancers. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2839-2848, 2012.     

Use of macrophages to deliver therapeutic and imaging contrast agents to tumors

Drug targeting to tumors with limited toxicity and enhanced efficacy of drug is one of the important goals for cancer treatment pharmaceutics. Monocytes/macrophages are able to migrate to tumor sites across the blood barriers by acting as Trojan horses carrying drug cargoes. Taking this advantage, we have intended to develop an efficient administration system using a biologically active carrier of mouse peritoneal macrophage bearing liposomal doxorubicin (macrophage-LP-Dox). We expect that this system could improve the cancer therapeutic efficacy through deeper penetration into tumor even hypoxic region behind tumor blood vessel. We first confirmed that macrophages containing iron oxides could migrate and infiltrate into tumors effectively by MR imaging. Next, we showed that doxorubicin (Dox) encapsulated with liposomes (LP-Dox) was successfully loaded into macrophages, in which the biological activity of macrophage and cytotoxicity of Dox against tumor cells were well preserved. Delivery of Dox into tumor tissue by systemic administration of macrophage-LP-Dox was verified in both subcutaneous and metastasis xenograft tumor models. Importantly, the effective inhibition of in vivo tumor growth was proved with this system. Our results provide the feasibility of macrophages-LP-drug as an active biocarrier for the enhancement of therapeutic effects in cancer treatment and open new perspectives for the active delivery of drugs.     

Large-scale automatic extraction of side effects associated with targeted anticancer drugs from full-text oncological articles

Targeted anticancer drugs such as imatinib, trastuzumab and erlotinib dramatically improved treatment outcomes in cancer patients, however, these innovative agents are often associated with unexpected side effects. The pathophysiological mechanisms underlying these side effects are not well understood. The availability of a comprehensive knowledge base of side effects associated with targeted anticancer drugs has the potential to illuminate complex pathways underlying toxicities induced by these innovative drugs. While side effect association knowledge for targeted drugs exists in multiple heterogeneous data sources, published full-text oncological articles represent an important source of pivotal, investigational, and even failed trials in a variety of patient populations. In this study, we present an automatic process to extract targeted anticancer drug-associated side effects (drug–SE pairs) from a large number of high profile full-text oncological articles.We downloaded 13,855 full-text articles from the Journal of Oncology (JCO) published between 1983 and 2013. We developed text classification, relationship extraction, signaling filtering, and signal prioritization algorithms to extract drug–SE pairs from downloaded articles. We extracted a total of 26,264 drug–SE pairs with an average precision of 0.405, a recall of 0.899, and an F1 score of 0.465. We show that side effect knowledge from JCO articles is largely complementary to that from the US Food and Drug Administration (FDA) drug labels. Through integrative correlation analysis, we show that targeted drug-associated side effects positively correlate with their gene targets and disease indications. In conclusion, this unique database that we built from a large number of high-profile oncological articles could facilitate the development of computational models to understand toxic effects associated with targeted anticancer drugs.     

药物缓释载体材料在医药领域中的研究及应用

背景：药物缓释就是将小分子药物与高分子载体以物理或化学方法结合,在体内通过扩散、渗透等控制方式,将小分子药物以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的。 目的：总结药物缓释载体材料特征及其在医药领域中的应用。 方法：以“药物缓释、载体材料、生物降解、壳聚糖、聚乳酸、海藻酸钠”为中文关键词,以“Drug delivery,carrier material,biodegradable,chitosan,polylactic acid, sodium alginate”为英文关键词,采用计算机检索中国期刊全文数据库、PubMed数据库(1993-01/2010-11)相关文章。纳入高分子生物材料-药物缓释载体等相关的文章,排除重复研究或Meta分析类文章,共入选31篇文章进入结果分析。 结果与结论：壳聚糖和聚乳酸是当前在药物缓释体系中应用较多的材料,它是将小分子药物与高分子载体以物理或化学方法结合, 以适当的浓度持续地释放出来,从而达到充分发挥药物功效的目的,较单一生物材料具有显著优越性,具有更好的生物相容性和生物可降解性。目前很多研究仍处于实验阶段,还有一些问题有待于解决,如制剂质量方法不成熟,剂量较难控制,成本较高等。