ROS-responsive drug delivery systems for biomedical applications

In the field of biomedicine, stimuli-responsive drug delivery systems(DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species(ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes,whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore,ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field.

Metal-Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

Investigation of metal–organic frameworks(MOFs)for biomedical applications has attracted much attention in recent years.MOFs are regarded as a promising class of nanocarriers for drug delivery owing to well-defined structure,ultrahigh surface area and porosity,tunable pore size,and easy chemical functionalization.In this review,the unique properties of MOFs and their advantages as nanocarriers for drug delivery in biomedical applications were discussed in the first section.Then,state-ofthe-art strategies to functionalize MOFs with therapeutic agents were summarized,including surface adsorption,pore encapsulation,covalent binding,and functional molecules as building blocks.In the third section,the most recent biological applications of MOFs for intracellular delivery of drugs,proteins,and nucleic acids,especially aptamers,were presented.Finally,challenges and prospects were comprehensively discussed to provide context for future development of MOFs as efficient drug delivery systems.

Nanodiamonds with powerful ability for drug delivery and biomedical applications:Recent updates on in vivo study and patents

Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical,chemical,optical and biological properties,making them significant active moiety carriers for biomedical application.These are known as the most‘captivating’crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era.Alongside,it becomes increasingly important to find,ascertain and circumvent the negative aspects associated with nanodiamonds.Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry.To take advantage of nanodiamond potential in drug delivery,focus has to be laid on its purity,surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment.This review emphasizes on the basic properties,synthesis techniques,surface modification techniques,toxicity issues and biomedical applications of nanodiamonds.For the development of nanodiamonds as an effective dosage form,researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.

Progress in oncolytic viruses modified with nanomaterials for intravenous application

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor cells.Simultaneously,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer cells.However,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely restricted.In recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection.The most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and effectiveness.The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

Application of Liquid Chromatography-Tandem Mass Spectrometry in Determination of Veterinary Drug Residues

With the long -term and irrational use of veterinary drugs and drug additives in the process of animal feeding, the veterinary drug resi- dues in animals and their additives can be ingested into the human body and pose potential threat to human health. Detection of veterinary drug resi- dues are extremely important practical significance to protect the ecological environment and human health. In recent years, liquid chromatography -tandem mass spectrometry has been widely used in vetednary drug residue detection because of its applicability, qualitative and quantitative fea- tures as well as high sensitivity. This article summarized the application of liquid chromatography -tandem mass spectrometry in detection veterinary drug residues from feed, animal products, arid udne as well as illicit drugs and harmful additives.

Progress in the development and application of plant-based antiviral agents

Plant virus disease is one of the major causes of biological disasters in agriculture worldwide. Given the complexity of transmission media and plant disease infection mechanisms, the prevention and control of plant viral diseases is a great challenge, and an efficient green pesticide is urgently needed. For this reason, when developing candidate drug leads to regulate plant viruses, pesticide experts have focused on characteristics such as low pesticide resistance, eco-friendliness, and novel mechanism. Researchers have also theoretically investigated the molecular targets of viruses infecting agricultural crops. Antiviral screening models have been constructed based on these molecular targets, and the mechanisms of commercial drugs and high-activity compounds have been extensively investigated. After screening, some compounds have been applied in the field and found to have good commercial prospects; these drugs may be used to create new green antiviral pesticides to control plant viruses. This paper reviews the screening, mode of action, development and application of recently used plant-based antiviral agents.

Thinking outside the liver: Induced pluripotent stem cells for hepatic applications

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

Advances in studies of phospholipids as carriers in skin topical application

Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advances of the phospholipids carriers in transdermal delivery systems. The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal delivery system.

Recent advances in network pharmacology applications in Chinese herbal medicine

网络药理学是基于系统生物学理论和生物系统网络分析来设计药物的一门新兴学科。它综合探索药物对疾病网络的干预和影响,揭示多分子药物协同治疗疾病的奥秘。这些概念反映了多组分、多靶点和系统调控的思想,与中医辨证论治的研究思路有许多相似之处,强调对病因病机的全面认识。网络药理学可以用来预测和鉴别中药的靶标和有效成分,阐明其作用机制,系统地解释处方的用药规律,探索真实世界处方的规律,发现新的适应症和新的活性化合物,研究药物重新定位等。本文系统总结了网络药理学在中药研究中的应用,展示了网络药理学在中药研究中的重要价值。

Helicobacter pylori neutrophil-activating protein:From molecular pathogenesis to clinical applications

Helicobacter pylori(H.pylori)neutrophil-activating protein(HP-NAP)was originally identified as a virulence factor of H.pylori for its ability to activate neutrophils to generate respiratory burst by releasing reactive oxygen species.Later on,HP-NAP was also found to be involved in the protection of H.pylori from DNA damage,supporting the survival of H.pylori under oxidative stress.This protein is highly conserved and expressed by virtually all clinical isolates of H.pylori.The majority of patients infected with H.pylori produced antibodies specific for HP-NAP,suggesting its important role in immunity.In addition to acting as a pathogenic factor by activating the innate immunity through a wide range of human leukocytes,including neutrophils,monocytes,and mast cells,HP-NAP also mediates adaptive immunity through the induction of T helper cell typeⅠresponses.The pro-inflammatory and immunomodulatory properties of HP-NAP not only make it play an important role in disease pathogenesis but also make it a potential candidate for clinical use.Even though there is no convincing evidence to link HP-NAP to a disease outcome,recent findings supporting the pathogenic role of HP-NAP will be reviewed.In addition,the potential clinical applications of HP-NAP in vaccine development,clinical diagnosis,and drug development will be discussed.

Smart stimuli-responsive drug delivery systems in spotlight of COVID-19

The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.

国家医保谈判药品在我院遴选评价的转化应用探索

目的:积极推进国家医保谈判药品的常态化落地,提升国家医保谈判药品的供应保障水平及透明化程度,促进药品回归临床价值。方法:依据2022年5月河北省卫生健康委员会组织制定下发的《河北省三级公立医疗机构用药(化学药品)目录遴选评价表(试行)》中的评价体系,针对拟遴选入院的61个国家医保谈判药品,从有效性、药学特性、安全性、经济性、其他属性5个维度进行综合评价。结果:47个国家医保谈判西药中,29个药品前3项评分≥50分;34个药品前4项评分≥60分;39个药品总分≥60分;24个药品前3项评分≥50分、前4项评分≥60分、总分≥70分;7个药品前3项评分<50分、前4项评分<60分、总分<70分。14个国家医保谈判中药中,同时满足前3项评分≥50分、前4项评分≥60分、总分≥70分的药品数量与同时满足前3项评分<50分、前4项评分<60分、总分<70分的药品数量均为6个。结论:本研究运用量化评价体系对国家医保谈判药品的有效性、药学特性、安全性、经济性等指标进行全方位评价,赋予量化分值,构建满足医疗机构需求的国家医保谈判药品综合评价数据库,通过综合分数来提取出“优”的国家医保谈判药品,过程快速、科学、公正、透明。

基于多学科协作管理模式结合PDCA质量管理工具对中药注射剂的管控效果分析

目的:探讨多学科协作管理模式结合PDCA质量管理工具用于医院中药注射剂管理的成效,为促进中药注射剂的合理应用提供参考。方法:成立多学科协作管理小组,运用PDCA质量管理工具,采取综合干预措施管控河北省中医院(以下简称“该院”)中药注射剂的临床应用。以2020年为干预前、2021年为第1阶段干预后、2022年为第2阶段干预后,对比干预效果。结果:干预前,该院中药注射剂合理使用率为92.38%(3 008/3 256),第1阶段干预后、第2阶段干预后分别升高至94.64%(3 740/3 952)、97.34%(3 766/3 869),与干预前的差异有统计学意义(P<0.001),中药注射剂不合理使用情况得到明显改善。第2阶段干预后,在超疗程、未冲管方面较第1阶段干预后明显改善,差异均有统计学意义(P<0.001),且未发现中西药混合输注、溶剂剂量不适宜、给药途径不适宜、溶剂种类选择不当等问题。干预后,中药注射剂相关不良反应占药品总不良反应的比例呈逐年降低趋势,尤其是第2阶段干预后较干预前明显降低,差异有统计学意义(P=0.013)。结论:在医院中药注射剂管理中运用多学科协作管理模式结合PDCA质量管理工具,可使管理质量显著提高,该方法值得在医院药事管理中推广。

分析多角度光散射在药物质量控制中的应用价值

多角度光散射技术在药物质量控制中有着广泛的应用,该检测技术能够直接针对大分子药物相对分子质量与分布情况进行测定,具有测定范围广以及准确度高等特点,能够为药物质量控制以及标准建立、修订等提供技术参考和指导。本文就多角度光散射技术的特点、原理及在药物质量控制中应用情况进行分析。

中医药联合医用水凝胶治疗疾病的策略及意义

背景:医用水凝胶是具有三维结构网络的新型功能高分子材料,具有出色的生物相容性,目前已在组织工程领域、药物载体领域有广泛研究,但基于组织工程探究医用水凝胶与中医药结合治疗疾病的研究还处于初期探索阶段。因此,通过对医用水凝胶机制作用的剖析,整合医用水凝胶与中医药在研究中联合应用的文章,进而更好地为科研工作者提供思路,对中医药与医用水凝胶联合应用具有重要意义。目的:基于组织工程研究探讨中医药联合医用水凝胶治疗疾病的策略及意义。方法:利用PubMed和中国知网数据库,检索有关中医药联合医用水凝胶在组织工程中应用的文献,检索时间为2010年1月至2022年11月,英文检索词为“hydrogel,traditional Chinese medicine,drug carrier,tissue engineering”,中文检索词为“医用水凝胶、中医药、药物载体、组织工程”。根据纳入与排除标准对所有文章进行初筛后,最终纳入61篇文章进行综述。结果与结论:①中医药联合医用水凝胶的应用虽然在关节内、组织器官内、软组织伤口和组织工程等方面有所涉及,但除了中医药结合水凝胶敷料在临床应用治疗软组织损伤外,其他方面尚处于基础实验阶段。②中医药联合医用水凝胶的发展有着巨大潜力和发展前景,但对于性能要求较高的凝胶在制造方面存在一定难度,理化性质精确掌握难度较大。③目前综合来看可注射水凝胶凭借着简便易用的特点,其在与中医药联合使用可延伸范围较广,可用于关节、器官和组织工程相关疾病的治疗;智能水凝胶有较高的灵敏度和可逆转化性也可满足特殊环境下的使用;将两者结合的中医药使用过程中还需要明确中药成分的作用机制。④中医药联合医用水凝胶治疗疾病的策略应着手于中医药对器官、组织、细胞的治疗作用联合适当种类的医用水凝胶进行匹配,可弥补传统中医给药方式和频繁给药的不足,在组织工程方面可以用水凝胶负载中药干预后的干细胞,或者同时负载中药和干细胞用于相关疾病的治疗。⑤在中医药联合医用水凝胶应用的未来研究中,还需要考虑:应当确保医用水凝胶生物性能可以量化,以不同材料不同制造工艺把握水凝胶特性,制造出所需要的符合应用条件的医用水凝胶;在中医药方面需要对已知中药单体、中药复方提取物的治疗效果和应用机制全面了解剖析,在更明了的机制下实现中医药与医用水凝胶更多更完美的结合;借助医学科技创新能力的不断提高,医用水凝胶可以创新性地结合中医药其他传统治疗方法比如针灸、推拿和拔罐等方式进行多角度运用。

人血白蛋白心外科围手术期应用合理性多中心回顾性调查分析

目的调查国内多地区心外科围手术期人血白蛋白(HSA)临床应用情况,结合临床指南评价其应用合理性,为促进HSA的合理应用提供参考。方法回顾性收集2019年4—6月全国8家医院行心外科手术患者的病历资料,统计患者一般资料、HSA的用法用量、疗程、费用,用药前后血清白蛋白水平等信息,分析HSA的使用情况,建立相关评价标准对其应用的合理性进行评价。结果共纳入患者449例,HSA用药合理率为81.1%。用药疗程>2~5 d居多,HSA应用总量在50~99 g居多,用药目的主要为提高胶体渗透压、减轻渗出以改善间质水肿和术后扩充血容量。结论保证心外科围手术期HSA的合理应用,防止血液制品滥用需要引起临床的高度重视。

某三级甲等医院人工智能辅助医药领域专利申请及授权现状分析

目的促进医院人工智能(AI)辅助医药领域相关专利的发展。方法利用解决方案式全球专利智能检索分析平台(HimmPat)提供的专利检索及分析功能,检索某三级甲等医院(截至2023年10月31日)涉及AI辅助医药领域的相关专利数据,分析该领域专利的申请和授权情况、申请法律状态、授权专利类型、具体技术领域、合作申请情况等。结果该院共申请专利130件,其中38件(29.23%)获得授权;16件(12.31%)为合作申请专利,授权率为50.00%。2017年开始出现相关专利申请,之后申请量呈先逐年增加后下降又回升趋势,授权量自2021年起迅速增长;在审专利申请有56件(43.08%),失效专利申请较多(36件,27.69%);获授权专利中发明专利占比较大(34件,授权率为26.98%),实用新型专利授权仅4件。具体技术集中在智能诊疗和智能健康管理领域。结论该院AI辅助医药领域相关专利申请量保持增长态势,但还存在专利管理人才缺乏、涉及技术领域单一、合作申请少等问题。建议医院巩固智能诊疗和智能健康管理方面的专利申请,加强专利管理人才队伍建设,建立高价值专利培育体系,规范医疗数据标准,培养复合型人才,深化与企业合作,并推动专利转化及在高附加值的AI辅助药品研发方面的研究。

基于《江苏省医疗机构药品遴选与临床应用评价体系》的氟维司群的临床综合评价研究

目的:对新型内分泌治疗药物氟维司群进行药品评价,为医疗机构遴选该药品提供参考。方法:参考药品说明书、临床指南、相关文献、权威数据平台和网站等,使用《江苏省医疗机构药品遴选与临床应用评价体系》的评价维度、评价细则及评价方法,对氟维司群进行药品量化评分与评价。结果:基于评价体系的氟维司群总评分为55分:其中,必要性8分,安全性6分,有效性20分,经济性5分,创新性3分,适宜性4分,可及性4分,其他情况5分。结论:本研究中所用方法可供医疗机构的药物遴选与评价参考,能够帮助医疗卫生机构快速地评价与遴选药品,可为临床用药提供参考。

化学仿制药中美双报注册策略分析

目的分析中国加入国际人用药品注册技术协调会(ICH)后,国内企业仿制药中美双报注册的现状及其注册要求,以期为国内企业提供参考。方法比较分析中国和美国化学仿制药注册申报路径、通用技术文档(common technical document,CTD)、药学研究和生物等效性研究等方面的具体要求,总结我国企业中美双报的优势和劣势,强调中美双报过程中需要关注的重点。结果2017年以来,国内企业在美国的仿制药申请(abbreviated new drug application,ANDA)获批数量显著增加;中美仿制药注册在CTD申报的要求、药学研究资料、生物等效性试验的设计等方面有差异也有共性,国内企业在注册申报时需对这些差异予以重视,深入理解两国的技术要求。结论从研发立项、质量标准、参比制剂选择、生物等效性试验设计等方面分别提出了建议,以期为我国企业中美双报提供参考,加快药品在两国上市速度,提升国内企业的国际竞争力。

体内药物分析技术在临床药学工作中的应用进展

目的探讨体内药物分析技术在临床药学工作中的应用进展。方法查阅相关文献,对临床样本的特点、临床常用的体内药物分析方法、体内药物分析在临床药学中的应用以及现存的问题进行综述。结果和结论近年来,随着临床个体化治疗、精准治疗的需求增大,以及分析技术的不断发展,体内药物分析技术广泛地应用于临床药学工作中,成为促进临床合理用药、提高个体化治疗水平、减少药品不良反应发生的重要辅助技术之一。但在实际应用中,还存在血液采样的侵入性阻碍采样、药物监测结果解释能力弱和临床检测方法等仍有待完善的问题。这些问题应当引起重视,并在后续的研究和应用中不断改善和解决。