纳米药物免疫毒性研究进展

纳米药物由于粒径小等特性,极易进入体内,并透过多种生理屏障与免疫细胞或细胞表面蛋白相互作用,发生特异性反应,诱发免疫应答,增强或降低机体的免疫功能。此外,免疫系统自身的复杂性和纳米药物类型多样性增加了研究纳米药物免疫毒性的难度。纳米药物对机体可能具有免疫抑制或免疫刺激包括抗原性、佐剂特性和炎症反应等免疫学特性,不同的纳米药物也已发现可以诱导机体产生不同程度的免疫反应。本文就纳米药物的免疫学特性、免疫系统与纳米药物的相互作用以及不同纳米药物免疫毒性研究方法进行综述。     

鱼藤酮纳米凝胶的制备与表征

目的以三嵌段聚酯聚乙二醇共聚物 （PLGA PEG PLGA）为材料制备鱼藤酮纳米凝胶。方法采用薄膜分散 水化法制备鱼藤酮纳米凝胶,并分别对其粒径分布、药物分散状态和药物释放特性等理化特性进行研究。结果鱼藤酮纳米凝胶平均粒径为120 nm,多分散系数0.190,药物主要以非晶型均匀分散在纳米凝胶中;纳米凝胶具有良好的缓释效果,10 d释放＜40%,药物的释放与释放介质和纳米凝胶中的药物含量密切相关。结论该方法成功制备了难溶性药物鱼藤酮的纳米凝胶制剂,能够显著改善其水溶性和药物释放特性。     

聚合物纳米药物制剂生物分析方法及药动学研究进展

聚合物纳米药物制剂因其具有长循环、可降低免疫原性、不良反应小等优点,得到了越来越多的关注,已经成为纳米药物制剂研究的热点。然而,真正成功应用于临床的聚合物纳米药物制剂的数量非常少,药代动力学行为不理想是导致这一现象的主要原因之一。聚合物纳米制剂作为载药粒子进入体内之后,会释放出游离药物和聚合物辅料,游离药物是发挥药效的物质基础,而聚合物辅料则有可能会引起辅料-药物相互作用,因此,聚合物纳米药物制剂药代动力学研究的关注点不应该仅仅局限于游离药物本身,应该同时关注载药粒子、游离药物、聚合物辅料及其代谢物在体内的动态变化,这就为聚合物纳米药物制剂的生物分析方法提出了新的要求和挑战。基于此,本文简要介绍了聚合物纳米药物制剂的常用生物分析方法色谱分析法的特点及适用范围,概述了聚合物纳米药物制剂在体内的吸收、分布、代谢和排泄,希望能够为聚合物纳米药物制剂的药代动力学研究、安全性和有效性评价提供借鉴和参考。     

药物纳米结晶的生物药剂学特性概述

药物纳米结晶在人体内的吸收和分布等过程中显示出的独特生物药剂学性质己引起研究者的广泛关注.本文综述了药物纳米结晶在人体内的吸收特性、不同给药方式的影响及其在靶向性研究中的应用,旨在深入了解药物纳米结晶的体内生物药剂学特性,以期更好地指导药物纳米结晶的剂型研发.     

脂质体纳米药物制剂的生物分析方法及药代动力学研究进展

脂质体纳米药物制剂是一种被脂双分子层囊泡结构包裹的具有纳米尺度的新型药物制剂。脂质体作为药物递送载体,具备生物相容性良好、在体内可被生物降解以及定位靶向性强等优点。应用脂质体纳米药物递送系统,可在一定程度上改善某些药物在人体内的药代动力学行为及药效,减轻不良反应。脂质体纳米药物进入人体后,会释放游离型药物,因而体内会同时存在负载型脂质体纳米药物和游离型药物。负载型药物是药物的贮库,游离型药物与药物的药效和不良反应有关,因此,脂质体药代动力学研究应该同时关注负载型药物和游离型药物。游离药物、脂质体粒子及其材料的精准分析是脂质体体内定量研究的一个难点。本篇综述介绍了脂质体纳米药物的前处理方法,总结了脂质体纳米药物的生物分析方法及其药代动力学的研究进展,希望能够为脂质体纳米药物制剂的研究开发提供参考。     

《纳米药物非临床安全性评价研究技术指导原则》解读

随着纳米技术的迅速发展,纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物由于具有特殊的纳米尺度效应和纳米结构效应等理化特性,从而具有特殊的生物学特性,使其吸收和组织分布等药代动力学特征可能发生变化,并进而影响其安全性和有效性。同时,由于纳米药物的特殊性,纳米药物的非临床安全性评价在普通药物非临床安全性评价的基础上,有许多特别需要关注之处。中国于2021年8月25日发布了《纳米药物非临床安全性评价研究技术指导原则》,本文对该指导原则进行全面解读,着重介绍纳米药物非临床安全性评价的关注要点,并结合案例进行阐述,旨在为纳米药物的研发者提供参考。     

纳米抗体在G蛋白偶联受体研究中的应用

G蛋白偶联受体(G protein-coupled receptors, GPCRs)含7次跨膜螺旋,是人体最大的膜蛋白受体家族,在多种疾病的进程中起关键作用,也是非常重要的药物靶点。目前上市药物中有30%～40%为靶向GPCRs药物。纳米抗体(nanobody)又称为单域抗体(single-domain antibody, sdAb),因其分子质量小、生化性能良好、与“裂缝或空腔”亲和力高等特性,成为研究GPCRs的重要工具。且纳米抗体具有较长的互补决定区3 (complementarity determining region 3, CDR3)环,可使其深深地插入受体的配体结合口袋中,与GPCRs高效结合。本文归纳了纳米抗体的特性及其在GPCRs研究中的相关应用,并简要介绍了目前靶向GPCRs纳米抗体的产生途径,为纳米抗体在GPCRs研究应用方面提供新的思路和方法。     

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。     

关于举办2012年中国药物制剂大会的通知(第二轮)

以纳米技术为基础的纳米药物传递系统研究是现代医药发展的重要方向之一。纳米药物载体的发展,为现代给药系统的研究提供了新途径,它所具有的优越特性预示着其在临床疾病治疗和诊断中具有十分广泛的应用前景。为使我国药学工作者及时把握国际纳米药物传递系统的研发动态,获取国内外最新研究成果信息,为国内外从事新型纳米药物传递系统研发的专业人员提供展示的平台,推动我国纳米应用研究的发展,中国药学会定于2012年9月20日至21日在四川省成都市举办     

壳聚糖载药纳米粒研究进展

目的介绍壳聚糖载药纳米粒近年来的研究进展。方法总结壳聚糖纳米粒的制备方法、释药特性、生物摄取及其应用。结果不同的制备方法可得到不同粒径和表面特性的壳聚糖纳米粒。壳聚糖纳米粒改变了壳聚糖的摄取机制，广泛应用于药物的器官靶向、DNA转染效率提高、药物的非注射途释给药等方面。结论壳聚糖纳米粒作为一种新型的药物载体，具有重要的研究开发价值。     

Nanomedicine-based drug targeting for psoriasis: potentials and emerging trends in nanoscale pharmacotherapy

Introduction: Psoriasis is a T-cell mediated autoimmune inflammatory skin disease recognized by skin surface inflammation, epidermal proliferation, hyperkeratosis, angiogenesis and anomalous keratinization. Currently, various pharmacotherapies are available for it; however, pharmacotherapy based on conventional formulations can provide therapeutic benefits only to a limited extent. Recent advancement in nanotechnology-based nanomedicines has led to the possibility of improving the efficacy and safety of pharmacotherapeutic agents for psoriasis.

Areas covered: This review covers the brief pathophysiology of psoriasis, available medications and its associated challenges in treatment. Collective accounts of various drugs acting on different molecular targets of psoriasis and the role of nanomedicines in their effective targeting are discussed. Moreover, newer approaches in psoriatic therapy such as combination drug targeting and physical techniques of topical permeation enhancement along with nanomedicines are also discussed.

Expert opinion: Novel nanomedicines (such as liposomes, polymeric nanoparticles, etc.) have shown their potential in improving therapeutic benefits of antipsoriatic drugs by increasing their therapeutic efficacy with minimal toxicity. Nevertheless, while the results on animal models using nanomedicine-based drug targeting of psoriasis via different route seem promising, lack of sufficient evidence in a clinical setup is a constraint and more clinical studies on the efficacy and safety of nanomedicines in psoriasis therapy are required.     

Summary Report of PQRI Workshop on Nanomaterial in Drug Products: Current Experience and Management of Potential Risks

At the Product Quality Research Institute (PQRI) Workshop held last January 14–15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.KEY WORDS: nanomaterials, nanomedicine, nanotechnology, PQRI, risk management, USFDA     

Current approaches of nanomedicines in the market and various stage of clinical translation

Compared with traditional drug therapy, nanomedicines exhibit intriguing biological features to increase therapeutic efficiency, reduce toxicity and achieve targeting delivery. This review provides a snapshot of nanomedicines that have been currently launched or in the clinical trials, which manifests a diversified trend in carrier types, applied indications and mechanisms of action. From the perspective of indications, this article presents an overview of the applications of nanomedicines involving the prevention, diagnosis and treatment of various diseases, which include cancer, infections, blood disorders, cardiovascular diseases, immuno-associated diseases and nervous system diseases, etc. Moreover, the review provides some considerations and perspectives in the research and development of nanomedicines to facilitate their translations in clinic.     

The Growing Field of Nanomedicine and Its Relevance to Pharmacy Curricula

The field of nanomedicine is a rapidly growing scientific domain. Nanomedicine encompasses a diverse number of active pharmaceutical ingredients. Submissions of Investigational New Drugs and New Drug Applications have risen dramatically over the last decade. There are over 50 nanomedicines approved for use by the US Food and Drug Administration (FDA). Because of the fundamental role pharmacists will play in therapeutic and administrative decisions regarding nanomedicines, it is imperative for future pharmacists to gain exposure early in their training to this rapidly evolving class of drugs. This commentary describes nanomedicines, discusses current regulatory challenges, and provides recommendations for judicious incorporation of nanomedicine topics into the Doctor of Pharmacy curriculum based on emerging pharmaceutical and clinical science applications.     

Nanomedicine(s) under the microscope

Depending on the context, nanotechnologies developed as nanomedicines (nanosized therapeutics and imaging agents) are presented as either a remarkable technological revolution already capable of delivering new diagnostics, treatments for unmanageable diseases, and opportunities for tissue repair or highly dangerous nanoparticles, nanorobots, or nanoelectronic devices that will wreak havoc in the body. The truth lies firmly between these two extremes. Rational design of "nanomedicines" began almost half a century ago, and >40 products have completed the complex journey from lab to routine clinical use. Here we critically review both nanomedicines in clinical use and emerging nanosized drugs, drug delivery systems, imaging agents, and theranostics with unique properties that promise much for the future. Key factors relevant to the design of practical nanomedicines and the regulatory mechanisms designed to ensure safe and timely realization of healthcare benefits are discussed.     

纳米药物的监督管理

目的 为加强我国纳米药物监管,促进纳米药物的健康发展提供借鉴.方法 综述了欧洲、美国、加拿大以及日本药监部门对纳米药物发展的应对策略以及采取的具体措施.结果与结论 纳米药物的发展给现有的药品监督管理带来挑战,发达国家的药监部门正在积极了解纳米药物的性质,研究纳米药物质量控制方法和监督管理策略.     

Carbon nanotubes as nanomedicines: from toxicology to pharmacology

Various biomedical applications of carbon nanotubes have been proposed in the last few years leading to the emergence of a new field in diagnostics and therapeutics. Most of these applications will involve the administration or implantation of carbon nanotubes and their matrices into patients. The toxicological and pharmacological profile of such carbon nanotube systems developed as nanomedicines will have to be determined prior to any clinical studies undertaken. This review brings together all the toxicological and pharmacological in vivo studies that have been carried out using carbon nanotubes, to offer the first summary of the state-of-the-art in the pharmaceutical development of carbon nanotubes on the road to becoming viable and effective nanomedicines.     

Role of Particle Size in Translational Research of Nanomedicines for Successful Drug Delivery: Discrepancies and Inadequacies

Despite significant research progress in substantiating the therapeutic merits of nanomedicines and the emergence of sophisticated nanotechnologies, the translation of this knowledge into new therapeutic modalities has been sluggish, indicating the need for a more comprehensive understanding of how the unique physicochemical properties of nanoparticles affect their clinical applications. Particle size is a critical quality attribute that impacts the bio-fate of nanoparticles, yet precise knowledge of its effect remains elusive with discrepancies among literature reports. This review aims to address this scientific knowledge gap from a drug development perspective by highlighting potential inadequacies during the evaluation of particle size effects. We begin with a discussion on the major issues in particle size characterization along with the corresponding remedies. The influence of confounding factors on biological effects of particle size, including colloidal stability, polydispersity, and in vitro drug release, are addressed for establishing stronger in vitro-in vivo correlation. Particle size design and tailoring approaches for successful nanoparticulate drug delivery beyond parenteral administration are also illustrated. We believe a holistic understanding of the effect of particle size on bio-fate, combined with consistent nanoparticle manufacturing platforms and tailored characterization techniques, would expedite the translation of nanomedicines into clinical practice.     

Recent progress in dendrimer-based nanomedicine development

Dendrimers offer well-defined nanoarchitectures with spherical shape, high degree of molecular uniformity, and multiple surface functionalities. Such unique structural properties of dendrimers have created many applications for drug and gene delivery, nanomedicine, diagnostics, and biomedical engineering. Dendrimers are not only capable of delivering drugs or diagnostic agents to desired sites by encapsulating or conjugating them to the periphery, but also have therapeutic efficacy in their own. When compared to traditional polymers for drug delivery, dendrimers have distinct advantages, such as high drug-loading capacity at the surface terminal for conjugation or interior space for encapsulation, size control with well-defined numbers of peripheries, and multivalency for conjugation to drugs, targeting moieties, molecular sensors, and biopolymers. This review focuses on recent applications of dendrimers for the development of dendrimer-based nanomedicines for cancer, inflammation, and viral infection. Although dendrimer-based nanomedicines still face some challenges including scale-up production and well-characterization, several dendrimer-based drug candidates are expected to enter clinical development phase in the near future.     

Liposomal nanomedicines

Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal nanomedicines, represent an advanced class of drug delivery systems, with several formulations presently on the market and many more in clinical trials. Over the past 20 years, a variety of techniques have been developed for encapsulating both conventional drugs (such as anticancer drugs and antibiotics) and the new genetic drugs (plasmid DNA containing therapeutic genes, antisense oligonucleotides and small interfering RNA) within LNs. If the LNs possess certain properties, they tend to accumulate at sites of disease, such as tumours, where the endothelial layer is ‘leaky’ and allows extravasation of particles with small diameters. These properties include a diameter centred on 100 nm, a high drug-to-lipid ratio, excellent retention of the encapsulated drug, and a long (> 6 h) circulation lifetime. These properties permit the LNs to protect their contents during circulation, prevent contact with healthy tissues, and accumulate at sites of disease. The authors discuss recent advances in this field involving conventional anticancer drugs, as well as applications involving gene delivery, stimulation of the immune system and silencing of unwanted gene expression. Liposomal nanomedicines have the potential to offer new treatments in such areas as cancer therapy, vaccine development and cholesterol management.