细胞膜修饰纳米粒药物递送系统的研究进展

纳米粒是药物递送系统研究的热点之一,但仍存在体内循环时间短,易被网状内皮系统识别和清除等缺点,限制了其临床应用。近年来,天然细胞膜成分和纳米技术的结合为解决这些问题提供了新的方案。一种由纳米粒核和细胞膜壳组成的新型仿生系统极大地改善了纳米粒的性能。用细胞膜修饰的纳米粒具有独特的功能,如延长血液循环时间,提高主动靶向和增强细胞内化等功能。本文综述了细胞膜修饰纳米粒药物递送系统的最新进展及其在癌症治疗方面的应用前景。     

壳聚糖纳米粒载体的应用研究进展

目的介绍壳聚糖纳米粒载体在药物、基因递送等方面的研究应用进展,为其在新领域的应用提供依据。方法广泛查阅中外文有关文献,整理分析归纳了其中27篇文献内容。结果壳聚糖纳米粒载体在药物和基因递送方面已经有诸多研究应用。结论壳聚糖纳米粒载体是一种有前途的非病毒递送载体,其特性和应用有待进一步探索。     

两亲性壳聚糖衍生物在药物递送中的研究进展

壳聚糖是一种来源丰富的碱性多糖,具有良好的生物相容性和生物可降解性,但是其差的溶解性限制了壳聚糖在医药领域的应用。为了提高壳聚糖的溶解性,研究者对壳聚糖进行两亲性改性,通过选择不同的亲水、疏水基团,设计合成了两亲性壳聚糖衍生物。并利用其在水溶液中的自组装性能,形成两亲性壳聚糖纳米粒,用于多种药物的递送,以达到增加药物溶解性、稳定性、降低药物毒性和提高生物利用度等目的。本文综述了两亲性壳聚糖衍生物的合成方法,以及其在药物递送系统中的应用。     

壳聚糖及其衍生物在药物递送中的研究进展

壳聚糖是自然界中存在的唯一的带正电的碱性氨基多糖,具有来源丰富、无毒、低免疫原性、良好的生物可降解性和生物相容性等优点。壳聚糖的活性氨基和羟基,经各种化学修饰如羧基化、巯基化、季铵化、疏水修饰、长循环修饰和靶向修饰,可获得具有特殊功能特性的衍生物,广泛用作药物和基因的载体材料。是近年来药剂学领域的研究热点。本文就近年来壳聚糖及其衍生物在药物递送中的研究进展作一综述。     

壳聚糖纳米粒用作基因递送载体的初步研究

目的初步研究基因壳聚糖纳米粒的性质和转染活性。方法用复凝聚法制备纳米粒;用透射电镜观察形态;用纳米粒度分析仪测定粒径、多分散度和zeta电位;用荧光分光光度法测定基因包封率;用凝胶阻滞分析和荧光扫描测定基因在纳米粒中的位置;用体外基因转染实验定性评价纳米粒的转染活性。结果纳米粒形态多呈球形,平均粒径为218.9 nm,多分散度为0.276,zeta电位为+21.2 mV;基因包封率为99.6%;凝胶阻滞分析和荧光扫描表明基因几乎全部被包裹在纳米粒内部,表面吸附很少;体外基因转染实验表明基因壳聚糖纳米粒能够转染人胚胎肾细胞(HEK293)和肝癌细胞(HepG2),基因能够在这两种细胞中表达。结论壳聚糖纳米粒能将基因递送到细胞内并且基因能够表达,因此可以用作基因药物载体。     

红细胞作为药物递送系统的研究进展

传统的治疗药物存在稳定性差、摄取效率低、细胞毒性大以及靶向能力差等缺点。因此需要安全的药物传递系统来延长药物在体内的循环和暴露。以红细胞为载体的新型药物递送系统凭借其良好的生物相容性、低免疫原性以及长循环时间而逐渐成为理想的药物递送平台。基于红细胞的药物递送系统包括多种类型,主要有红细胞膜包裹纳米颗粒载药系统和基因工程红细胞等。另外,对红细胞进行功能化修饰,可显著增强靶向性,进一步开发和扩大红细胞载药体系在多种疾病治疗中的应用。本研究介绍了以红细胞为载体的化学药物及疫苗的递送方法,重点讨论了仿生纳米红细胞药物递送系统及其对机体各部位的靶向性研究,并且总结了近年来基因工程红细胞策略的研究进展。     

纳米药物递送系统在蛋白质药物中的应用

纳米技术是指用单个原子、分子制造或将大分子物质加工成粒径在1～100 nm范围内的物质的技术。由于其应用于药物制剂领域具有诸多优点,如增强药物的靶向性、提高药物生物利用度、改善药物稳定性等,因此在药物制剂领域,尤其在药物递送系统的研究中被广泛应用。蛋白质药物递送是药物研发中非常重要的内容,通过用合适的递送系统来改变其自身不足和缺点,成为蛋白质药物制剂研发的热点。本文对纳米药物递送系统在蛋白质药物方面的应用进行综述,并对下一步的研究方向进行展望。     

基于丝素蛋白的纳米粒药物递送系统研究进展

丝素蛋白(silk fibroin, SF)是一种天然高分子,具有一定的水溶性、结构修饰性、良好的生物相容性和生物降解性,可作为药物递送的载体材料。SF载药纳米粒可控制药物释放、减少不良反应、提高治疗效果,是一种有前景的药物递送系统。本综述介绍了SF的基本特征、SF载药纳米粒的制备方法和SF在纳米粒药物递送系统的应用,在此基础上,对SF载药纳米粒的进一步发展进行了展望。     

磷脂-壳聚糖自组装纳米粒的研究进展

目的:了解磷脂-壳聚糖自组装纳米粒的研究进展,为新型药物递送载体的研究和开发提供思路。方法:以"壳聚糖""磷脂""纳米粒""自组装""Chitosan""Lecithin""Phospholipid""Nanoparticles""Self-assembled"等为关键词,在中国知网、万方、维普、PubMed、Elsevier、SpringerLink等数据库中组合查询2002年-2018年11月发表的相关文献,对磷脂-壳聚糖自组装纳米粒的形成机制和微观结构、制备方法以及作为药物递送载体的应用等相关研究进行综述。结果与结论:共检索到相关文献499篇,其中有效文献34篇。带正电荷的壳聚糖与磷脂中负电荷基团通过静电相互作用自组装形成脂溶性致密内核、壳聚糖包裹带正电荷水化外壳的核壳结构纳米粒;采用常规的溶剂注入法制得的磷脂-壳聚糖自组装纳米粒,具有良好生物相容性,能促进药物渗透吸收和提高生物利用度等,在口服、经皮、眼部及鼻腔黏膜等给药系统具有广泛的应用前景。今后可考虑对壳聚糖或纳米粒表面进行结构修饰和功能性设计,并进一步探索和研究如何精准调控自组装纳米粒的微观结构、尺寸大小、药物分布以及功能等。     

无机中空纳米粒与纳米管在药物/基因递送中的应用

相对于纳米材料的大小、形状及成分,无机纳米材料的生物相容性主要由表面功能化决定,对无机中空纳米材料进行适当的表面修饰可以减小其毒性;纳米管、纳米壳和中多孔纳米粒由于其中空及多孔结构,以及表面易功能化特点而成为极有吸引力的药物/基因载体;无机纳米材料的生物学效应和其在光、电及物理学方面综合的优良性能引起了人们极大兴趣,吸引了大量的相关研究。本文主要讨论了中空及多孔纳米材料在纳米医学特别是药物/基因递送应用方面近期的研究进展。     

壳聚糖在靶向制剂中的应用进展

壳聚糖是一种天然高分子化合物，壳聚糖及其衍生物具有优良的生物相容性和生物可降解性，在制药业有广阔的应用前景。综述了近几年来壳聚糖及其衍生物在靶向制剂中的应用。     

Review: doxorubicin delivery systems based on chitosan for cancer therapy

Objectives This review sheds insight into an increasingly popular polymer that has been widely explored as a potential drug delivery system. The abundant, biodegradable and biocompatible polysaccharide chitosan, with many other favourable properties, has been favoured as a drug delivery system for the purposes of encapsulating and delivery of doxorubicin with reduced side‐effects. Key findings Doxorubicin is frequently used as a frontline chemotherapeutic agent against a variety of cancers. It has largely been able to demonstrate anti‐tumour effects, though there are major shortfalls of doxorubicin, which include serious side‐effects such as cardiomyopathy and myelosuppression, and also an ever‐present danger of extravasation during drug administration. In view of this, drug delivery systems are currently being explored as alternative methods of drug delivery in a bid to more effectively direct doxorubicin to the specific lesion site and reduce its systemic side‐effects. Liposomes and dendrimers have been tested as potential carriers for doxorubicin; however they are not the focus of this review. Summary Recent advancements in doxorubicin and chitosan technology have shown some preliminary though promising results for cancer therapy.     

Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review

Chitosan is a promising biopolymer for drug delivery systems. Because of its beneficial properties, chitosan is widely used in biomedical and pharmaceutical fields. In this review, we summarize the physicochemical and drug delivery properties of chitosan, selected studies on utilization of chitosan and chitosan-based nanoparticle composites in various drug delivery systems, and selected studies on the application of chitosan films in both drug delivery and wound healing. Chitosan is considered the most important polysaccharide for various drug delivery purposes because of its cationic character and primary amino groups, which are responsible for its many properties such as mucoadhesion, controlled drug release, transfection, in situ gelation, and efflux pump inhibitory properties and permeation enhancement. This review can enhance our understanding of drug delivery systems particularly in cases where chitosan drug-loaded nanoparticles are applied.     

壳聚糖微/纳米粒在定向给药系统中的应用研究

目的：介绍壳聚糖微/纳米粒在新型定向给药系统中的应用,为发展安全高效的壳聚糖微/纳米粒定向给药系统提供参考。方法：综合近年来出版的有关文献,对壳聚糖基本性质,定位给药于各组织部位进行了探讨。结果：壳聚糖微/纳米粒可应用于脑、眼、鼻、口、肺、胃、小肠、结肠等器官靶向给药。结论：壳聚糖微/纳米粒作为一种新型药用辅料,在定位给药系统中已经得到了开发和应用。     

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

Oral drug delivery systems (ODDSs) have various advantages of simple operation and few side effects. ODDSs are highly desirable for colon-targeted therapy (e.g. ulcerative colitis and colorectal cancer), as they improve therapeutic efficiency and reduce systemic toxicity. Chitosan/alginate nanoparticles (CANPs) show strong electrostatic interaction between the carboxyl group of alginates and the amino group of chitosan which leads to shrinkage and gel formation at low pH, thereby protecting the drugs from the gastrointestinal tract (GIT) and aggressive gastric environment. Meanwhile, CANPs as biocompatible polymer, show intestinal mucosal adhesion, which could extend the retention time of drugs on inflammatory sites. Recently, CANPs have attracted increasing interest as colon-targeted oral drug delivery system for intestinal diseases. The purpose of this review is to summarize the application and treatment of CANPs in intestinal diseases and insulin delivery. And then provide a future perspective of the potential and development direction of CANPs as colon-targeted ODDSs.     

Calcium carbonate nanoparticles as cancer drug delivery system

Introduction: Calcium carbonate (CaCO₃) has broad biomedical utilizations owing to its availability, low cost, safety, biocompatibility, pH-sensitivity and slow biodegradability. Recently, there has been widespread interest in their application as drug delivery systems for different groups of drugs. Among them, CaCO₃ nanoparticles have exhibited promising potential as drug carriers targeting cancer tissues and cells. The pH-dependent properties, alongside the potential to be functionalized with targeting agents give them the unique property that can be used in targeted delivery systems for anticancer drugs. Also, due to the slow degradation of CaCO₃ matrices, these nanoparticles can be used as sustained release systems to retain drugs in cancer tissues for longer times after administration.

Areas covered: Development of drug delivery carriers using CaCO₃ nanoparticles has been reviewed. The current state of CaCO₃ nanoparticles as cancer drug delivery systems with focus on their special properties like pH-sensitivity and biodegradability has also been evaluated.

Expert opinion: According to our review, CaCO₃ nanoparticles, owing to their special characteristics, will have a potential role in safe and efficient cancer treatment in future.     

Stimuli-responsive nanoscale drug delivery systems for cancer therapy

Abstract

Currently, with the rapid development of nanotechnology, novel drug delivery systems (DDSs) have made rapid progress, in which nanocarriers play an important role in the tumour treatment. In view of the conventional chemotherapeutic drugs with many restrictions such as nonspecific systemic toxicity, short half-life and low concentration in the tumour sites, stimuli-responsive DDSs can deliver anti-tumour drugs targeting to the specific sites of tumours. Owing to precise stimuli response, stimuli-responsive DDSs can control drug release, so as to improve the curative effects, reduce the damage of normal tissues and organs, and decrease the side effects of traditional anticancer drugs. At present, according to the physicochemical properties and structures of nanomaterials, they can be divided into three categories: (1) endogenous stimuli-responsive materials, including pH, enzyme and redox responsive materials; (2) exogenous stimuli-responsive materials, such as temperature, light, ultrasound and magnetic field responsive materials; (3) multi-stimuli responsive materials. This review mainly focuses on the researches and developments of these novel stimuli-responsive DDSs based on above-mentioned nanomaterials and their clinical applications.     

Smart drug delivery systems for precise cancer therapy

Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.     

多柔比星纳米递药系统在三阴性乳腺癌靶向治疗中的应用

三阴性乳腺癌为高度恶性肿瘤。多柔比星是三阴性乳腺癌的常规化疗药物,该药药理作用是通过嵌入DNA碱基对之间,干扰基因转录,抑制mRNA和DNA合成。常规给药方式对正常组织损伤严重。多柔比星纳米递药系统借助肿瘤酸性微环境实现缓控释效应,多柔比星与肿瘤细胞的组织相容性增加,对正常组织影响较小。该系统有效抑制和杀灭肿瘤细胞,明显减轻正常细胞的细胞毒性。本文综述了近年来多柔比星靶向纳米递药系统的应用,以期开拓三阴性乳腺癌的的靶向治疗新视野。     

A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy

A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light, and have great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system (NDDS) to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A (DTA) fragment-encoded plasmids to tumor sites. The expression of DTA was induced by exposure to blue light. Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond, and PEGylated hyaluronic acid modified with RGD peptide, accumulated in tumor tissues and were actively internalized into 4T1 cells via dual targeting to CD44 and α_vβ₃ receptors. The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure. In vitro studies showed that light-induced DTA expression reduced 4T1 cell viability and induced apoptosis. Furthermore, the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4T1 tumor xenograft model, which resulted in excellent antitumor effects, reduced tumor angiogenesis, and no systemic toxicity. The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.