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。     

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。     

核-壳结构的脂质-聚合物杂化纳米粒的研究进展

核-壳结构的脂质-聚合物杂化纳米粒（CSLPHNs）是以具有生物可降解性的聚合物纳米粒为核,外层包覆单层或多层具有生物膜仿生性的脂质壳而形成,结合了纳米粒和脂质体的双重优点,具有粒径小、载药量高、生物相容性好及缓控释给药等优势,在药物递送系统中应用甚广。笔者在查阅近年国内外文献的基础上归纳了CSLPHNs的基本特性、制备方法及在眼部给药、肿瘤治疗及临床诊断成像中的最新研究进展。     

聚合物-脂质纳米粒用于增强酪氨酸血症I型治疗性碱基编辑器质粒的肝靶向递送研究（英文）

酪氨酸血症I型是一种罕见的常染色体隐性遗传病,目前尚无有效的治疗方法。近年来,以碱基编辑器为代表的基因编辑技术已被报道用于酪氨酸血症I型的治疗。然而,由于生理屏障的存在,碱基编辑器递送困难。在本研究中,我们构建了一种靶向去唾液酸糖蛋白受体的聚合物-脂质纳米递送系统,用于改善酪氨酸血症I型治疗性核酸药物的递送效率。我们首先合成了一种生物可降解性丙烯酸酯-氨基醇共聚物用于递送碱基编辑器质粒,其转染效率显著优于市售转染试剂Hieff Trans^TM。随后,共聚物纳米粒与DOPE-PEG-Gal NAc自组装形成聚合物-脂质纳米粒,用于增强纳米粒的肝脏递送效率。在体外转染实验中,包载Fah-p CMV-ABE6.3-EGFP碱基编辑器质粒的聚合物-脂质纳米粒表现出了良好的肝细胞选择性,其转染效率是游离质粒的70倍以上。研究表明,携带肝靶向配体的聚合物-脂质纳米递送系统能够有效增强治疗性碱基编辑器质粒的肝靶向递送效率并为酪氨酸血症I型的基因治疗提供了一种潜在的递送载体。     

壳聚糖纳米粒作为药物递送系统在癌症治疗中的应用

癌症是威胁人类生存的恶性疾病之一。近年来,利用纳米技术将药物靶向递送到肿瘤部位,可以增加疗效并降低毒性,为癌症治疗带来了新希望。壳聚糖是自然界唯一存在的碱性多糖,具有良好的生物相容性和生物可降解性。此外,其反应位点多,可制成不同性质的衍生物,广泛用于药物递送系统和组织工程支架,在生物医药领域具有重要的应用价值。本综述对近年来壳聚糖纳米粒在抗癌药物递送方面的研究进展进行介绍,重点介绍了壳聚糖纳米粒的制备、被动靶向、主动靶向和刺激-响应药物递送系统方面的研究进展。     

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。     

细胞膜仿生递药系统在肿瘤治疗中的研究进展

纳米药物递送系统在肿瘤精准医疗领域具有良好的应用前景,但有机或无机合成的纳米材料存在制备过程繁琐和易被机体内免疫系统识别、清除等问题。受自然界生物系统的启发,生物细胞膜介导的仿生纳米递药系统近年来成为研究热点。生物膜仿生递药系统通过机体内源性细胞膜对纳米载体表面进行包覆修饰,有效地将天然生物膜“自体”性质和“人工”功能载体的优势相融合,赋予其肿瘤靶向性,低免疫原性和血液长循环等特点。基于纳米药物和细胞膜仿生技术在肿瘤精准医疗领域的研究进展,对细胞膜仿生修饰纳米粒的实验基础、膜仿生纳米递药系统的构建及在肿瘤靶向化疗、免疫治疗、光热治疗上的应用三方面进行综述,并对未来研究进行展望。     

用于肺部疾病治疗的细胞膜涂层仿生纳米粒递送体系研究进展

肺易受外界侵扰,造成多种急性和慢性肺部疾病。采用功能化纳米粒作为载体可携带药物穿透多重肺生理屏障进入肺病变部位,但存在靶向性差、治疗效率低等问题。细胞膜涂层仿生纳米粒作为药物载体,由于保留其源细胞特性,具有免疫系统逃逸、主动靶向、炎症趋化、穿过生理屏障等特点,近年来被大量应用于肺部疾病的治疗研究。本综述总结了近年来多种细胞膜仿生纳米粒在肺部疾病治疗中的应用,并进行了分类论述,其中细胞膜来源包括红细胞膜、血小板膜、巨噬细胞膜、中性粒细胞膜、肺上皮细胞膜、肺表面活性剂、内皮细胞膜、癌细胞膜、细菌膜和混合膜等。本综述旨在为细胞膜涂层仿生纳米粒治疗肺部疾病提供新思路。     

上市核酸药物及其脂质纳米递送载体研究进展

核酸作为新一代生物技术药物,不但可以从本源上治疗疾病,而且在技术和生产层面均具有显著的平台化特征,因此在医疗领域具有广阔的应用前景。然而,核酸在体内外稳定性差,递送效率低,极大限制了其成药性。近年来,以可离子化脂质为基础的脂质纳米粒展示出良好的临床应用潜力,并在核酸新冠疫苗中得到了验证。脂质纳米粒能够凭借其独特的结构和理化性质特征,在体内展现出较高的递送效率和较好的安全性,为未来核酸药物的临床应用提供了更多可能。本文围绕核酸药物自身特点及其临床应用面临的屏障,结合已获批上市核酸药物,重点阐述其递送载体脂质纳米粒成功的关键要素,并对领域内尚待解决的问题进行展望。     

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。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.