纳米技术用于动脉粥样硬化诊疗的研究进展

动脉粥样硬化(atherosclerosis,AS)是一种慢性炎症性疾病,其特征是脂质、免疫细胞和纤维成分在动脉壁中积聚。目前临床诊断技术缺乏准确性和特异性,药物很难直接靶向斑块实现有效治疗。因此,如何对AS易损斑块进行准确诊断和有效干预、实现治疗药物的精准递送,成为目前临床迫切需要解决的问题。近年来,随着纳米科技和纳米材料的快速发展,纳米技术在监测易损斑块形成、提高斑块内药物浓度等方面表现出了独特优势,本文按照纳米材料类型分别对其进行综述,以期为纳米技术在AS疾病精准诊疗领域的研究和应用提供有益借鉴。     

免疫细胞靶向递送机制与载药技术研究进展

免疫细胞介导的药物靶向递送系统是使用免疫细胞为载体,利用其天然的组织或器官趋向性将药物选择性递送至特定病灶部位的制剂.本文系统介绍了免疫细胞的迁移级联特性,单核/巨噬细胞、中性粒细胞、T细胞和NK细胞等免疫细胞的类型及其作为药物递送载体的主要特点,以及免疫细胞与纳米制剂技术相结合的靶向递送载药策略,为同类研究提供参考.     

中性粒细胞介导的药物递送系统在肿瘤靶向治疗中的应用

目的通过综述中性粒细胞介导的药物递送系统在肿瘤靶向治疗中的应用,为纳米制剂递送的未来发展提供理论依据。方法查阅国内外相关文献91篇,对中性粒细胞与纳米制剂的结合策略、影响因素和发展前景等内容进行总结与分析。结果中性粒细胞是肿瘤生长、转移等过程的参与者之一,且因数量丰富、形态灵活,使得研究者们开始以中性粒细胞为靶点,设计中性粒细胞介导的纳米药物递送系统。目前,中性粒细胞与纳米制剂的结合策略主要有三种:中性粒细胞体外载药再回输、中性粒细胞体内载药和中性粒细胞仿生纳米粒。而影响中性粒细胞介导的纳米药物递送的因素主要包括影响中性粒细胞摄取、运输以及释放药物等多种因素。结论对中性粒细胞介导的药物递送系统应用于肿瘤治疗的策略进行理性评价与反思,将为纳米制剂递送的研究与发展提供更为完善的理论依据和实际应用价值。     

纳米药物载体的脑靶向评价方法

利用纳米药物载体将难以透过血脑屏障的药物递送入脑是脑靶向治疗的策略之一,纳米药物载体脑靶向特性的评价是相关研究的重要环节。本文对体外细胞模型和体内光学成像、药代动力学、行为学检测等方法,以及脑摄取参数等体内外评价指标进行了综述,为系统评价纳米药物脑靶向特性提供方法学依据。     

从纳米给药系统角度探讨阿尔茨海默病的治疗策略

阿尔茨海默病严重威胁人类健康,主要是血脑屏障限制了药物到达作用靶点,影响阿尔茨海默病的治疗.而纳米给药系统为药物的脑靶向递送提供了可能,对阿尔茨海默病的治疗有改善作用,本文从阿尔茨海默病的发病机制和常规治疗药物展开,重点从纳米给药系统角度进行介绍阿尔茨海默病的治疗策略,概述几种典型的治疗阿尔茨海默病的纳米给药系统,即脂质体、聚合物胶束、固体脂质纳米粒和聚合物纳米粒等.     

基于线粒体靶向纳米药物递送系统的设计及研究进展

线粒体参与能量提供、信号传导、细胞分化等诸多生理活动,在肿瘤的发生发展中起重要作用,以线粒体为靶标是一种癌症治疗新策略。利用纳米技术构建线粒体靶向纳米药物递送系统可改善传统药物溶解性,延长药物半衰期,提高其生物利用度及降低不良反应,有望解决肿瘤治疗中出现的耐药性问题。本综述着重于癌症治疗领域,介绍了线粒体靶向纳米药物递送系统用于癌症治疗的机制,并概述了近5年线粒体靶向纳米药物递送系统的设计思路、分类及应用研究,最后拓展分析了以线粒体为靶点的其他研究如仿生载体等,并讨论其存在的优势及不足,为未来纳米药物靶向线粒体的深入研究提供了依据。     

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。     

纳米载体介导的药物递送在阿尔茨海默病治疗中的研究进展

阿尔茨海默病（AD）是一种大脑功能渐进性恶化的中枢性疾病,最初的特征是认知缺陷,近期记忆和语言能力丧失,方向、解决问题和抽象思维障碍等,严重影响了患者的身心健康和生活质量。然而目前现有治疗药物只能减轻或暂时减缓AD的症状,但不能阻止其进展而达到治愈效果;同时神经系统血脑屏障的存在进一步限制了药物的利用度。为克服目前药物治疗瓶颈,药物靶向传递为驱动药物穿过血脑屏障并有效地进入大脑提供了新的治疗策略。针对近年来纳米技术的迅速发展以及基于纳米颗粒介导的药物递送为AD的治疗提供了可能,本文就纳米技术靶向治疗机制以及纳米载体介导的药物递送在AD预防与治疗中的研究进展作一综述,旨在为进一步开发AD治疗药物提供更多的理论依据。     

克服肿瘤多药耐药的药物共递送纳米载体的设计及研究新方向

多药耐药（multidrug resistance，MDR）是肿瘤治疗成功的主要障碍，药物共递送纳米载体因其肿瘤靶向、控制释放、一致的药动学曲线而被认为是克服MDR的有效策略。本综述总结了当前克服MDR的药物共递送纳米载体的设计思路，并分析了具有前景的研究方向，包括精确药物负载纳米载体、呈时序释放的纳米载体和对肿瘤微环境设计纳米载体，这些新兴策略为临床肿瘤治疗提供了新颖且更好的定制组合方案。     

纳米制剂在心肌缺血区域的靶向机制及应用

缺血性心脏病是严重威胁人类健康的疾病。至今为止,药物预处理和治疗依旧是心肌缺血预防和治疗的重要手段。但大多数抗心肌缺血药物缺乏组织特异性,同时由于缺血区域血液循环受阻,导致药物在缺血部位的分布往往不甚理想。靶向纳米制剂是一种治疗心血管疾病的新型给药策略。纳米制剂在体内主要可以通过"被动靶向"、"主动靶向"和"物理化学靶向"作用将药物递送至病变部位,提高药物在缺血区域的靶向性和释放率,从而改善药物治疗效果。本文对应用靶向纳米制剂治疗心肌缺血的疗效及机制研究作一综述。     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Nanomedicine for tumor therapy-current status and challenges

The field of nanomedicine in controlled drug delivery systems, especially for tumor targeting, has tremendously progressed over the past decades because of its plentiful benefits, such as biocompatibility, stability in blood circulation, and ability to reduce side effects. Although a large number of relevant papers are published every year, few nanodrugs are available for clinical treatment. The present review aimed to explore the barriers in nanomedicine delivery and tumor targeting. Rational design of nanomedicine should consider not only tumor heterogeneity, in vivo metabolism, and physicochemical properties, but also more efficient innovations in particulate formulations for clinical application.     

Emerging potential of stimulus-responsive nanosized anticancer drug delivery systems for systemic applications

The development of novel drug delivery systems based on well-defined polymer therapeutics has led to significant improvements in the treatment of multiple disorders. Advances in material chemistry, nanotechnology, and nanomedicine have revolutionized the practices of drug delivery. Stimulus-responsive material-based nanosized drug delivery systems have remarkable properties that allow them to circumvent biological barriers and achieve targeted intracellular drug delivery. Specifically, the development of novel nanocarrier-based therapeutics is the need of the hour in managing complex diseases. In this review, we have briefly described the fundamentals of drug targeting to diseased tissues, physiological barriers in the human body, and the mechanisms/modes of drug-loaded carrier systems. To that end, this review serves as a comprehensive overview of the recent developments in stimulus-responsive drug delivery systems, with focus on their potential applications and impact on the future of drug delivery.     

An insight to osmotic drug delivery

In a typical therapeutic regimen the drug dose and the dosing interval are optimized to maintain drug concentration within the therapeutic window, thus ensuring efficacy while minimizing toxic effects. For many decades treatment of acute disease or a chronic illness has been mostly accomplished by delivery of drugs to patients using various pharmaceutical dosage forms. The immediate release conventional dosage form does not provide the proper plasma concentration of drug for prolonged period. This results in the development of various controlled drug delivery system. Among which the osmotic drug delivery systems (ODDS) are gaining importance as these systems deliver the drug at specific time as per the path physiological need of the disease, resulting in improved patient therapeutic efficacy and compliance. They work on the principle of osmotic pressure for controlling the delivery of the drug. Osmotic drug delivery systems with their versatility and their highly predictable drug release rates offer various biomedical advantages when given parenterally like reduced dose, targeting of site, avoiding gastrointestinal stability, hepatic bypass of drug molecule and follows zero order kinetics. Osmosis is an aristocratic phenomenon that seizes the attention for its exploitation in zero-order drug delivery systems. The release of the drug is independent of pH and physiological factors of the GIT to a large extent. Optimizing semi-permeable membrane characteristics and osmotic agent can modulate delivery of drug from the system. This review highlights the theoretical concept of drug delivery, history, types of oral osmotic drug delivery systems, factors affecting the drug delivery system, advantages and disadvantages of this delivery system, theoretical aspects, applications, and the marketed status.     

Alternative drug delivery approaches for the therapy of inflammatory bowel disease

This article shall give an overview on drug delivery systems for new therapeutic strategies in the treatment of inflammatory bowel disease. The various features of the different approaches allowing locally restricted drug delivery to the inflamed colon are discussed including the main physiological and pathophysiological limitations for the different systems. Conventional drug delivery systems are tightly adapted from developments for colonic delivery by oral administration triggered by release mechanisms owing to the physiological environment that these systems encounter in the colonic region. The newer developments in this context aim for an increased selectivity of drug delivery by targeting mechanisms which have a closer relation to pathophysiological particularities of the disease. Therefore, we were focused especially on new strategies for such treatment including liposomal formulations, cyclodextrins, micro- or nanoparticles, viral gene therapy approaches, and others. Effective and selective delivery even of an otherwise nonspecifically acting drug could provide new therapeutic pathways in the treatment of inflammatory bowel disease.     

Drug delivery targets and systems for targeted treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that selectively attacks human joints. The common non-targeted treatment approaches lead to obvious side effect and systemtic complication for RA patients. Therefore, targeted drug delivery for treatment of RA has gained much attetntion in the past few years. In this paper, we reviewed the potential targets (folate receptor, angiogenesis, matrix metalloproteases, selectins, vasoactive intestinal peptide receptor andFc-γ receptor) that could be utilised to facilitate the specific delivery of drugs to the inflammed synovium and also presented different drug delivery systems for targeting RA, including the liposomes, various types of nanoparticles, polymeric micelles and the macromolecular prodrugs. The strategies combining nanotechnologies and ligand mediated active targeting for RA would be emphatically illustrated, which was expected to be helpful for identifying technologies and drug delivery methods for targeted treatment of RA.     

Role of nanotechnology in targeted drug delivery and imaging: a concise review

The use of nanotechnology in drug delivery and imaging in vivo is a rapidly expanding field. The emphases of this review are on biophysical attributes of the drug delivery and imaging platforms as well as the biological aspects that enable targeting of these platforms to injured and diseased tissues and cells. The principles of passive and active targeting of nanosized carriers to inflamed and cancerous tissues with increased vascular leakiness, overexpression of specific epitopes, and cellular uptake of these nanoscale systems are discussed. Preparation methods-properties of nanoscale systems including liposomes, micelles, emulsions, nanoparticulates, and dendrimer nanocomposites, and clinical indications are outlined separately for drug delivery and imaging in vivo. Taken together, these relatively new and exciting data indicate that the future of nanomedicine is very promising, and that additional preclinical and clinical studies in relevant animal models and disease states, as well as long-term toxicity studies, should be conducted beyond the "proof-of-concept" stage. Large-scale manufacturing and costs of nanomedicines are also important issues to be addressed during development for clinical indications.     

Nanomedicine and experimental tuberculosis: facts, flaws, and future

Nanoparticle-based drug delivery systems form the crux of nanomedicine and are suitable for targeting chronic diseases such as tuberculosis. Extensive experimental data supports the possibility of intermittent chemotherapy with key first-line as well as second-line antituberculosis drugs by employing synthetic or natural carriers, chiefly polymers. Besides sustained release of drugs in plasma and organs, other potential advantages of the system include the possibility of selecting various routes of chemotherapy; reduction in drug dosage, adverse effects, and drug interactions; and targeting drug-resistant and latent bacteria. On the other hand, the choice of carrier, large-scale production, stability, and toxicity of the formulation are some of the major issues that merit immediate attention and resolution. Nevertheless, keeping in view the hurdles in new antituberculosis drug development, nanomedicine has provided a sound platform and a ray of hope for an onslaught against tuberculosis. FROM THE CLINICAL EDITOR: Tuberculosis remains a major public health concern worldwide. In this paper, the role and significance of nanoparticle-based drug delivery systems are discussed for targeting tuberculosis, including strains that are drug resistant with conventional methods.     

An updated review of folate-functionalized nanocarriers: A promising ligand in cancer

The uncontrolled release of drugs in conventional drug delivery systems has led to the introduction of new nanotechnology-based drug delivery systems and the use of targeted nanocarriers for cancer treatment. These targeted nanocarriers, which consist of intelligent nanoparticles modified with targeting ligands, can deliver drugs to specified locations at the right time and reduce drug doses to prevent side effects. Folate is a suitable targeting ligand for folate receptors overexpressed on cancer cells and has shown promising results in the diagnosis and treatment of cancer. In this review, we highlight the latest developments on the use of folate-conjugated nanoparticles in cancer diagnosis and treatment. Moreover, the toxicity, biocompatibility and efficacy of these nanocarriers are discussed.     

The influence of pulmonary surfactant on nanoparticulate drug delivery systems

The pulmonary route is very attractive for drug delivery by inhalation. In this regard, nanoparticulate drug delivery systems, designed as multifunctional engineered nanoparticles, are very promising since they combine several opportunities like a rather uniform distribution of drug dose among all ventilated alveoli allowing for uniform cellular drug internalization. However, although the field of nanomedicine offers multiple opportunities, it still is in its infancy and the research has to proceed in order to obtain a specific targeting of the drug combined with minimum side effects. If inhaled nanoparticulate drug delivery systems are deposited on the pulmonary surfactant, they come into contact with phospholipids and surfactant proteins. It is highly likely that the interaction of nanoparticulate drug delivery systems with surfactant phospholipids and proteins will be able to mediate/modulate the further fate of this specific drug delivery system. In the present comment, we discuss the potential interactions of nanoparticulate drug delivery systems with pulmonary surfactant as well as the potential consequences of this interaction.