外泌体用于疾病诊疗和药物递送的研究进展

外泌体是细胞外囊泡的一种,作为特殊的细胞间通讯介质,携带蛋白质、核酸及脂质等,在生物体内各种生理、病理过程中发挥着重要作用。作为内源性纳米囊泡,外泌体具有体循环稳定性、良好的生物相容性、对组织和细胞的特异性靶向等优点,是理想的药物递送载体。外泌体为多种疾病的诊断和预后评估提供支持,同时作为一种非常有潜力的、安全、特异性强的内源性纳米药物载体具有广阔的应用前景。本文阐述外泌体的产生机制,对其提取分离方法特点进行总结,并围绕外泌体在免疫和炎症相关疾病、心血管系统疾病、神经系统疾病、肿瘤等疾病的应用机制进行讨论,以及作为药物载体的工程化修饰和主动靶向药物递送进行综述。     

生姜囊泡包载金纳米粒子的构建及用于骨肉瘤治疗的实验研究

目的 构建一种生物相容性好、创伤小、疗效好的光热治疗方法，用于骨肉瘤的治疗。方法 分别利用差速离心法和柠檬酸盐还原法制备生姜囊泡和金纳米粒子。通过孵育法使生姜囊泡包被金纳米粒子，形成生姜囊泡-金纳米粒子复合物。利用CCK8法考察生姜囊泡-金纳米粒子复合物的生物毒性。通过CCK8法评估生姜囊泡-金纳米粒子复合物对骨肉瘤治疗的疗效。结果 成功制备了生姜囊泡和金纳米粒子，通过生姜囊泡包载金纳米粒子成功构建了一种光热治疗方法。结论 生姜囊泡包载金纳米粒子的光热治疗方法，具有简单、生物相容性好、生物毒性低、疗效好等优点，有望用于骨肉瘤的治疗。     

外泌体在脑靶向递送中的应用

血脑屏障(blood brain barrier, BBB)限制了大部分药物的脑靶向递送,进而影响神经系统疾病有效治疗。外泌体作为细胞衍生的纳米囊泡,可参与物质的细胞间运输、介导细胞间通讯和调节机体生物功能等,具有低免疫原性、低毒性及可天然跨越BBB的优点,在脑靶向递送中发挥重要作用。本文概括了外泌体分类、来源、脑靶向递送机制及其在脑部疾病中发挥的作用,为其临床应用提供参考。     

胞外囊泡作为药物传递天然纳米载体的研究进展

细胞释放膦脂膜的小囊泡在细胞交流、抗原递呈、感染物的传递等方面起关键作用。胞外小囊泡携带各种蛋白、mRNA、microRNA(miRNA),象一个卡车运载"货物"一样,将携带的各种分子运载至远端的细胞。而且,被小囊泡包裹的分子可避免被体液中的酶降解,使胞外囊泡成为天然的、新颖的药物传递系统。该文综述了胞外囊泡的分类、组成、生物药物应用、以及作为药物传递载体在临床实验应用等方面的研究进展,为寻求新的药物传递系统治疗相关疾病提供理论基础。     

传递体透皮研究的最新进展

传递体(transfersomes)是一种自聚集泡囊,其主要组成成分为磷脂和表面活性剂(如胆酸钠、去氧胆酸钠等),亦称为柔性纳米脂质体.粒径多为几十个纳米,外观为胶体溶液.嵌人泡囊膜中的表面活性剂使泡囊具有高度的变形性.在外力的作用下,传递体与相同体积的纯水通过孔径数倍小于传递体直径的高分子膜的时间几乎相同,而普通脂质体通过高分子膜的时间明显延长.将传递体非封闭地涂抹于皮肤,可透过直径约为0.4 nm的皮肤角质层孔道,因此传递体有望成为大分子、小分子药物和水溶性、脂溶性药物的透皮载体.传递体一词由Cevc G等[1]首先提出,在随后的十几年中,Cevc G等在探索传递体的透皮机制并将数十种药物制备成传递体,经皮给药后产生了相应的药理效应.近年,国外每年均有传递体研究的文献报道,研究涉及的药物和内容也不断扩展.传递体中文一词在国内首次出现于丁平田[2]所写的一篇有关传递体研究综述.近年来,国内也不断出现有关传递体的研究报道.本文将对传递体的特性、体外透皮研究、体内透皮研究、稳定性、药效学研究及展望等方面作一介绍.     

含有奥硝唑纳米囊泡的改性明胶膜释药性能的研究

目的:研制含有载药纳米囊泡的明胶缓释膜,对比普通载药膜表征其释药性能。方法:结合超声波法和逆向蒸发法,制备了载药纳米囊泡,并通过共混的方法进一步得到了含有奥硝唑纳米囊泡的改性明胶膜(简称载药纳米囊泡膜)。通过透射电镜观察分析了载药纳米囊泡的形态以及稳定性,通过紫外分光光度法分别测试了载药纳米囊泡的包封率、载药量以及载药纳米囊泡、载药膜和载药纳米囊泡膜的累积释药曲线。结果:载药纳米囊泡粒径在50～150nm之间,能长期稳定地存在于膜材料中,载药量和包封率分别为0．18mg·mg~(-1)和32．15%。普通载药膜在11h左右达到释药平衡,而载药纳米囊泡膜释药平衡时间达到了22h左右。结论:载药纳米囊泡膜同时具有载药膜和载药纳米囊泡的药物释放性能,明显改善了载药膜的药物缓释性和突释现象,扩展了载药膜和载药囊泡的应用范围。     

治疗性外泌体的研究进展

外泌体是一种活细胞分泌的囊性小泡,携带大量具有组织或细胞特异性的蛋白质、脂质及遗传物质,可调控不同的生理活动,因此作为一类新兴的治疗药物被广泛研究。间充质干细胞(mesenchymal stem cells, MSCs)和树突状细胞(dendritic cells, DCs)衍生的外泌体是研究较为广泛的两类外泌体,已有许多临床前及临床研究表明其在肺部疾病、肝脏疾病、神经系统疾病及肿瘤等疾病中展现出良好的治疗效果。另外,巨噬细胞、肿瘤细胞和植物细胞等众多其他细胞衍生的外泌体也因其治疗潜力受到越来越多的关注。除了天然来源的外泌体,工程化外泌体的研究也取得许多进展。已报道的外泌体工程化手段种类繁多,如外泌体靶向修饰、外泌体包载活性成分等。本文总结了不同来源的治疗性外泌体的研究进展,并讨论了外泌体的应用前景与未来可能遇到的挑战。     

外泌体在2型糖尿病发病机制及诊疗标志物开发中的研究进展

外泌体是一种纳米级大小的细胞外分泌囊泡,具有脂质双分子层结构,可以携带多种DNA,RNA以及蛋白质等生物分子,是细胞间信号传递的重要载体.大量研究结果表明,外泌体及其内含物可通过多种途径影响胰岛素的分泌和组织敏感性,参与糖脂代谢和胰岛素抵抗的调控,在包括糖尿病在内的内分泌及代谢性疾病发生发展过程中发挥重要作用.本文就外...     

外泌体在心肌疾病中的研究进展

外泌体是具有脂双层膜的细胞外囊泡,其通过携带丰富的微小RNA(miRNA)等生物分子传递信息,是细胞间通讯的关键介质。外泌体通过参与炎症反应、内皮细胞损伤、心肌纤维化等过程来影响各种心肌疾病的发生发展,在心肌的损伤和修复中起着非常重要的作用。本文主要就近几年发现的外泌体在各种心肌疾病中的机制、诊断及治疗等方面的作用展开综述。     

基于酵母膜囊泡药物载体系统的构建与应用初探

酿酒酵母作为可食用真核微生物,具有安全性高、增殖快、成本低、易改造等特性,已广泛用于生产疫苗、抗体、胰岛素等。截至目前,酵母相关组分如细胞壁、酵母微囊体已被广泛用于肿瘤、炎症病毒感染、创伤后骨关节炎等疾病的治疗。其中,酵母细胞膜组成成分相对简单稳定,易于大规模提取。因此,本研究以酵母细胞膜材料为研究对象,构建酵母膜囊泡纳米系统,并初步探究其生物医学应用。通过共挤出法制备酵母质膜囊泡(Saccharomyces cerevisiae membrane vesicle, SMV),并对SMV的粒径与表面电位、药物装载与释放特性、稳定性、细胞安全性、体外治疗效果等进行探究。结果显示:SMV平均粒径为185.1 nm,通过共孵育及超声等方法有效包载姜黄素及二氧化硅纳米粒,并保持细胞膜蛋白特性。而且SMV具有良好的稳定性与生物相容性。此外, SMV可被巨噬细胞RAW 264.7有效摄取,包载姜黄素的SMV可有效清除巨噬细胞内的活性氧(ROS)。综上,本研究所制备的酵母质膜囊泡可有效递送姜黄素药物及包载纳米粒,有效被巨噬细胞摄取并降低ROS,为酵母膜材料的生物医学应用提供了新思路和新方法。     

肺部吸入给药装置的研究进展

目的介绍肺部吸入给药装置的使用情况及最新进展。方法参阅国内外代表性文献资料,以其中的36篇为依据对其进行分析、归纳和整理。结果阐明了肺部吸入治疗的优越性及原理,并对肺部给药的喷雾器、定量吸入器和干粉吸入器的种类、作用机制、优缺点以及发展方向加以综述。结论肺部吸入给药具有广阔的发展和应用前景。     

新型局部给药系统促进创伤愈合的研究进展

目的 皮肤组织的创伤修复是临床常见的问题,对于创伤的治疗手段多种多样。方法 对近几年的相关创伤愈合文献进行整理、分析和归纳。结果 阐述了皮肤组织愈合的机制及用于创伤治疗的新型局部给药系统。结论 新型的局部给药系统具有能够增加局部药物浓度、减少不良反应、促进伤口愈合、使用方便、提高患者依从性等特点,新型的给药系统用于治疗局部创伤具有巨大的市场潜力。     

Ultrasound-mediated drug delivery for cardiovascular disease

Introduction: Ultrasound (US) has been developed as both a valuable diagnostic tool and a potent promoter of beneficial tissue bioeffects for the treatment of cardiovascular disease. These effects can be mediated by mechanical oscillations of circulating microbubbles, or US contrast agents, which may also encapsulate and shield a therapeutic agent in the bloodstream. Oscillating microbubbles can create stresses directly on nearby tissue or induce fluid effects that effect drug penetration into vascular tissue, lyse thrombi or direct drugs to optimal locations for delivery.

Areas covered: The present review summarizes investigations that have provided evidence for US-mediated drug delivery as a potent method to deliver therapeutics to diseased tissue for cardiovascular treatment. In particular, the focus will be on investigations of specific aspects relating to US-mediated drug delivery, such as delivery vehicles, drug transport routes, biochemical mechanisms and molecular targeting strategies.

Expert opinion: These investigations have spurred continued research into alternative therapeutic applications, such as bioactive gas delivery and new US technologies. Successful implementation of US-mediated drug delivery has the potential to change the way many drugs are administered systemically, resulting in more effective and economical therapeutics, and less-invasive treatments.     

A new concept in colonic drug targeting: a combined pH-responsive and bacterially-triggered drug delivery technology

Background Current approaches to colonic drug delivery exploit one of two main physiological characteristics: the pH change or increase in bacterial numbers along the gastrointestinal tract. Here, we describe a new concept in targeted delivery, which combines these triggers to improve colonic delivery. Aim To assess the in‐vivo targeting performance of a novel colonic delivery coating comprising a mixture of pH‐responsive enteric polymer (Eudragit S) and biodegradable polysaccharide (resistant starch) in a single layer matrix film. Methods Tablets (radio‐labelled) were film‐coated with the dual‐mechanism coating and administered in a three‐way crossover study to eight healthy volunteers (i) without food, (ii) with breakfast or (iii) 30 min before breakfast. The site of intestinal disintegration was assessed using gamma scintigraphy. Results The coated tablets were able to resist breakdown in the stomach and small intestine. Consistent disintegration of the dosage form was seen at the ileocaecal junction / large intestine. The site of disintegration remained unaffected by feeding. Conclusions The dual‐mechanism (pH/bacterial) coating provides colon‐specificity. Each trigger mechanism has the capacity to act as a failsafe, ensuring appropriate targeting in the gastrointestinal tract. This platform technology has potential for systemic applications or the treatment of local disorders of the large intestine, such as inflammatory bowel disease.     

Challenges and trends in apomorphine drug delivery systems for the treatment of Parkinson's disease

 Parkinson’s disease (PD) is a chronic debilitating disease affecting approximately 1% of the population over the age of 60. The severity of PD is correlated to the degree of dopaminergic neuronal loss. Apomorphine has a similar chemical structure as the neurotransmitter dopamine and has been used for the treatment of advanced PD patients. In PD patients, apomorphine is normally administered subcutaneously with frequent injections because of the compound’s extensive hepatic first-pass metabolism. There is, hence, a large unmet need for alternative administrative routes for apomorphine to improve patient compliance. The present review focuses on the research and development of alternative delivery of apomorphine, aiming to highlight the potential of non-invasive apomorphine therapy in PD, such as sublingual delivery and transdermal delivery     

白藜芦醇治疗阿尔茨海默病的研究进展

神经退行性疾病是一种慢性进展性疾病,其特点是中枢神经系统神经元的逐渐丧失。由于血脑屏障的存在,经典的抗炎药物如类固醇激素和非甾体类抗炎药,对神经系统疾病的治疗作用有限。因此,开发新的抗炎药物,对于预防和治疗神经系统疾病具有重要的意义。白藜芦醇是一种有很强活性的天然多酚类物质,目前研究已显示其具有心血管保护、神经保护、免疫调节、肿瘤的化学预防作用。近年来还发现其具有抗神经炎症作用,可用于治疗神经精神性疾病,如帕金森病、阿尔茨海默病(AD)和亨廷顿症等。综述白藜芦醇对AD的保护作用及其机制研究进展,为进一步推进白藜芦醇用于防治AD的研究提供参考。     

曲妥珠单抗联合多西紫杉醇治疗Her-2阳性乳腺癌的临床研究

目的探析注射用曲妥珠单抗联合多西紫杉醇注射液治疗人类表皮生长因子受体2(Her-2)阳性乳腺癌的临床疗效。方法选取黄石市中心医院(普爱院区)2011年2月—2015年2月收治的乳腺癌患者86例作为研究对象,所有患者按照就诊顺序编号分为对照组和治疗组,每组各43例。对照组静脉滴注多西紫杉醇注射液75 mg/m2,1 h内滴完,间隔21 d重复给药,共给药4次。治疗组在对照组的基础上静脉滴注注射用曲妥珠单抗,将曲妥珠单抗溶于250 mL生理盐水中,首次剂量4 mg/kg,90 min内滴完,之后维持2 mg/kg,1次/周。观察两组的客观有效率、疾病控制率,同时比较治疗前后Her-2表达、细胞凋亡相关因子水平和不良反应发生情况。结果治疗后,对照组、治疗组的客观有效率、疾病控制率分别为60.5%、81.4%,70.0%、88.4%,两组比较差异有统计学意义(P0.05)。治疗后,两组患者Her-2(++)、(+++)比例显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组指标的降低程度优于对照组,两组比较差异有统计学意义(P0.05)。治疗后两组Caspase-3、DcR3、COX-2水平均显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组这些观察指标的降低程度优于对照组,两组比较差异有统计学意义(P0.05)。两组不良反应均以胃肠道反应、皮疹、白细胞减少、疲倦、心脏毒性等为主,但各种不良反应发生率的差异无统计学意义。结论注射用曲妥珠单抗联合多西紫杉醇注射液治疗Her-2阳性乳腺癌具有较好的临床疗效,可有效弱化Her-2表达,降低细胞凋亡相关因子水平,安全性佳,值得推广应用。     

Inhalable siRNA: potential as a therapeutic agent in the lungs

RNA interference (RNAi) is gaining increasing popularity both as a molecular biology tool and as a potential therapeutic agent. RNAi is a naturally occurring gene regulatory mechanism, which has a number of advantages over other gene/antisense therapies including specificity of inhibition, potency, the small size of the molecules and the diminished risk of toxic effects, e.g., immune responses. Targeted, local delivery of RNAi to the lungs via inhalation offers a unique opportunity to treat a range of previously untreatable or poorly controlled respiratory conditions. In this timely review we look at the potential applications of RNAi in the lungs for the treatment of a range of diseases including inflammatory and immune conditions, cystic fibrosis, infectious disease and cancer. In 2006 Alnylam initiated the first phase 1 clinical study of an inhaled siRNA for the treatment of respiratory syncytial virus. If its potential as a therapeutic is to be realized, then safe and efficient means of targeted delivery of small interfering RNA (siRNA) to the lungs must be developed. Therefore in this review we also present the latest developments in siRNA delivery to airway cells in vitro and the work to date on in vivo delivery of siRNA to the lungs for the treatment of a range of diseases.     

The cutting-edge technologies of siRNA delivery and their application in clinical trials

siRNA therapeutics allows precise regulation of disease specific gene expression to treat various diseases. Although gene silencing approaches using siRNA therapeutics shows some promising results in the treatment of gene-related diseases, the practical applications has been limited by problems such as inefficient in vivo delivery to target cells and nonspecific immune responses after systemic or local administration. To overcome these issues, various in vivo delivery platforms have been introduced. Here we provide an overview for three different platform technologies for the in vivo delivery of therapeutic siRNAs (siRNA–GalNAc conjugate, SAMiRNA technology, and LNP-based delivery method) and their applications in the treatment of various diseases. In addition, a brief introduction to some rare diseases and mechanisms of siRNA therapeutics-mediated treatment is described.     

Quantum dots: a powerful tool for understanding the intricacies of nanoparticle-mediated drug delivery

Nanoparticle-mediated drug delivery (NMDD) is an emerging research area that seeks to address many of the pharmacokinetic issues encountered with traditional systemically administered drug therapies. Although the field is still in its infancy, recent research has already highlighted the potential for improved drug delivery and targeted therapeutics; however, the real promise lies in combining drug therapy with diagnostic imaging, nucleic acid delivery/gene therapy and/or biosensing applications all in one engineered nanoparticle vector. In this review, the authors discuss the unique contributions that luminescent semiconductor nanocrystals or quantum dots (QDs) offer for NMDD, how they can function as a powerful nanoscale platform to understand this process at its most basic level, and even provide drug-related properties in certain circumstances. Selected examples from the current literature are utilized to describe both their potential and the contributions they have already made towards the design and implementation of NMDD vectors. Important related issues such as QD biofunctionalization and toxicity are also discussed. The paper concludes with a perspective of how this field can be expected to develop in the future.