壳聚糖纳米粒子基因载体的研究现状

背景:壳聚糖纳米粒子因其独有特性作为基因载体的研究日益增多.目的:综述了壳聚糖纳米粒子作为基因载体的研究进展,进一步促进基因治疗的效果.方法:应用计算机检索web of science 数据库和中国学术期刊数据库中2000-01/2011-04 关于壳聚糖及其衍生物作为基因载体研究的文章,在标题和摘要中以"chitosan,gene"或 "壳聚糖;基因"为检索词进行检索.选择内容与基因载体和壳聚糖相关的文章,初检得到120 篇文献,根据纳入标准选择31 篇文章进行综述.结果与结论:壳聚糖基因纳米粒子作为非病毒基因述文章的数量、主要结载体将在基因治疗领域中发挥举足轻重的作用,今后壳聚糖转基因体系的研究将更为深入.如何标记、可视跟踪壳聚糖DNA 复合物进入不同细胞的过程,明确其基因转染机制,进一步提高基因转染效率,使其尽快进入基因治疗临床应用是今后研究的主要方向.     

壳聚糖纳米粒子基因载体的制备与相关研究

目的制备CS/pcDNA3.1/GDNF混悬液,并对壳聚糖作为基因载体的相关性能进行检测。方法采用复凝聚法制备CS/pcDNA3.1/GDNF混悬液,观察壳聚糖纳米粒子的物理性能,稳定性,基因结合效率,基因保护功能,缓慢释放效果及基因负载力和负载率。结果壳聚糖大小为106-228nm,性质稳定,具有良好的基因携带功能,能够有效地保护所携带基因,基因负载力及基因负载率较高。结论应用复凝聚法制得壳聚糖纳米粒子,能够满足基因载体的需要,是一个较理想的基因载体。     

壳聚糖季铵盐作为基因递送载体的初步研究

背景:非病毒载体因其安全性好而在基因治疗领域赢得了广泛的关注,各种各样的非病毒载体处在不断的研究中,壳聚糖季铵盐作为一种新的生物材料,同样也具有作为基因递送载体的潜质.目的:考察壳聚糖季铵盐体外基因转染活性,寻求一种新的非病毒基因载体递送系统.设计、时间及单位:对比观察实验,于2008-04/12在浙江省医学科学院生物工程所完成.材料:质粒pcDNA3.1-EGFP为浙江省医学科学院生物工程实验室保存.以3-氯-2-羟丙基三甲基氯化铵作为改性剂制备壳聚糖季铵盐,用复凝聚法制备载基因纳米粒.方法:凝胶阻滞实验分析壳聚糖季铵盐包裹质粒的能力,DNase Ⅰ的保护实验分析载基因纳米粒的抵抗核酸酶降解的能力,体外基因转染实验评价纳米粒的体外转染活性,用倒置荧光显微镜观察和流式细胞仪测定转染结果.通过考察转染液中有无牛血清和递送不同剂量的基因对转染效率的影响,寻求本递送系统较好的转染条件.另外,用MTT法测定壳聚糖季铵盐的细胞毒性.主要观察指标:壳聚糖季铵盐和pcDNA 3.1-EGFP以何种比例结合形成的纳米粒、转染液中有无牛血清,质粒的量为多少时对人胚肾T细胞的转染效率足最高的;不同浓度的壳聚糖季铵盐对细胞生长的影响.结果:壳聚糖季钱盐纳米粒能转入人胚肾T细胞,虽然转染效率略逊丁聚乙烯亚胺,但是细胞毒性明显小于聚乙烯亚胺.壳聚糖季铵盐纳米粒转染细胞72 h后效率较高,经综合分析,当pcDNA质量为2 μg,壳聚糖季铵盐和pcDNA以质量比为5结合形成的纳米粒,在无血清条件下对人胚肾T细胞进行转染,转染效率足最高的.结论:壳聚糖季铵盐纳米粒能将基因递送到细胞内,并且报告基因能在细胞内表达.因此,壳聚糖季铵盐用做基因递送的载体系统值得进一步的研究.     

阳离子聚合物基因载体的理论研究

目的:介绍阳离子聚合物非病毒基因载体的种类,并分析它们各自的特点和作用.资料来源:以基因治疗,非病毒载体,阳离子聚合物,壳聚糖,环糊精为检索词,检索清华同方数据库(1980-01/2009-01).以gene therapy,non-viral vectors,Cationic polymer,chitosan,cyclodextrin为检索词,检索sciencedirect数据库(1980-01/2009-01).文献检索语种限制为英文和中文.资料选择:纳入阳离子聚合物作为非病毒基因载体的实验研究,排除其他形式基因载体的研究.结局评价指标:①细胞毒性.②基因表达率.③转染效率.结果:计算机初检得到154篇文献,根据纳入排除标准,对阳离子聚合物作为菲病毒基因载体的种类和治疗作用进行分析.目前,应用于基因治疗的载体主要有病毒载体和非病毒载体两种.病毒载体转染效率高,但存在免疫原性高、毒性大、目的基因容量小、靶向特异性差、制备较复杂及费用较高等缺点.因此,人们愈来愈重视非病毒载体的研究.阳离子聚合物作为非病毒基因载体显示出巨大的优势和潜力.它不但可以降低药物在细胞内的蓄积和毒性,还可以通过自身的降解来控制基因的释放.阳离子聚合物用作非病毒基因治疗载体包括多聚赖氨酸类共聚物、聚氨酯、聚乙烯亚胺阳离子共聚物、聚磷腈类、壳聚糖类及其衍生物和环糊精及其衍生物.结论:阳离子非病毒载体相比于其他非病毒载体,具有毒性低,基因转染率高,释药可控制等优点,是一种相对安全、高效的非病毒基因载体.     

壳聚糖作为基因载体及其改性

学术背景:基因治疗是近年来全球研究的热点,其最大障碍是缺乏有效的基因载体.非病毒性载体比病毒性载体具有更高的安全性,因而越来越受到人们关注.壳聚糖具有优良的生物相容性、生物可降解性、低毒以及高正电荷.是一种良好的非病毒性基因载体.带正电荷的壳聚糖能与带负电荷的DNA形成聚电解质复合物,有效复合保护质粒DNA免遭DNase酶解,使基因得以传递和表达.目的:概述壳聚糖作基因载体及其改性研究所取得的有意义的最新研究进展.检索策略:应用计算机检索Science Direct,Springer,Wiley数据库和中国期刊全文数据库1991-01/2007-12的有关文献,检索关键词为"壳聚糖、基因载体、DNA、进展".共检索到425篇相关文献.其中英文文献217篇,中文文献208篇.对文献进行筛选,选取关键文章,对同一领域的文献选择近期发表或权威杂志的文献,排除重复研究的文章.最后70篇被选用.文献评价:所选用的70篇文献中,60篇为英文文献,10篇为中文文献;其中10篇为综述,其余均为实验研究论文.资料综合:壳聚糖有优良的生物相容性、生物可降解性,无免疫原性,是当今最具潜力的非病毒性基因载体之一.通过优化壳聚糖的分子质量、脱乙酰度、N/P比、血清浓度和介质的pH值等可对壳聚糖的转染效率和细胞吸收进行调控.化学改性壳聚糖,尤其是偶联配体可传递基因进入靶细胞.结论:改性后的壳聚糖可作为潜在的优良基因载体.     

纳米粒子基因复合体应用于脊髓损伤治疗的实验研究

目的:观察壳聚糖纳米粒子胶质细胞源性神经营养因子基因复合体(CS-nano/pcD-NA3.1/GDNF)对脊髓损伤(SCI)的治疗作用.方法:Wistar大鼠170只,随机分为5组:A组(椎板切除+SCI-CS-nano/pcDNA3.1/GDNF,n=40),B组(椎板切除+SCI+GDNF基因治疗,n=40),C...     

壳聚糖及其衍生物作为纳米药物载体的研究与应用

背景：壳聚糖由于其独特的优点在药物载体研究领域中受到越来越多的关注。目的：综述壳聚糖基纳米药物载体的体内生物效应及安全性研究,包括其药效研究、药物代谢、组织分布以及体内毒性。方法：应用计算机检索CNKI、万方数据库和PubMed数据库中1998-01/2010-05关于以壳聚糖及其衍生物为材料制备的纳米粒子和载药纳米粒子体内药效学、药代动力学和毒性试验的文章,中文以＂壳聚糖＂和＂纳米粒子＂和＂体内＂或＂药效＂或＂药代动力学＂或＂组织分布＂或＂毒性＂为主题词,英文以＂chitosan and nanoparticle and in vivo＂或＂chitosan and nanoparticle and pharcodynamic or pharmacok inetic or biodistribution or toxicity＂为关键词进行检索。选择文章内容与纳米粒子体内实验相关,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到166篇文献,根据纳入标准选择43篇文章进行综述。结果与结论：从所检索到的文献进行总结分析,壳聚糖及其衍生物可作为蛋白类、细胞毒类和核酸类药物及诊断试剂等的载体,其载药纳米粒子与原型药物相比,显示出更长的体内循环时间、更好的药效和更小的毒副作用,体内药效和组织分布等生物效应和安全性均不同,研究方法也有所不同。     

壳聚糖载体介导关节内基因转移：转染效率与基因产品的关系

目的:分析壳聚糖-DNA超微颗粒在关节内的转基因效应。方法:实验于2005-09/2006-06在上海交通大学医学院健康科学研究所骨科细胞与分子生物学实验室完成。实验材料:①模型制备:采用切断内侧副韧带,切除内侧半月板的方法制备骨关节炎兔模型。②基因产品:白细胞介素(interleukin,IL)1Ra基因、IL-10基因。实验分组:15只新西兰兔按随机数字表法分为3组:①空载体对照组(n=3),造模后5d两侧膝关节关节腔注射400μL壳聚糖-PcDNA3.1溶液,共3次,每48h1次。②IL-1Ra基因治疗组和IL-10基因治疗组,每组6只,造模后5d对照侧膝关节关节腔分别注射20μg裸DNA(PcDNA3.1-IL-1Ra或PcDNA3.1-IL-10),实验侧膝关节关节腔注射400μL壳聚糖-DNA超微颗粒(含20μgIL-1Ra或IL-10),注射次数及间隔时间同空载体对照组。实验评估:①采用酶联免疫吸附分析及免疫组织化学检测IL-1Ra和IL-10基因的表达和分布。②苏木精-伊红染色和甲苯胺蓝染色观察骨关节炎软骨组织学变化。结果:纳入新西兰兔15只,均进入结果分析。①IL-1Ra和IL-10基因在关节滑液中的表达:空载体对照组及IL-1Ra基因治疗组对照侧膝关节滑液中未检测到IL-1Ra表达,实验侧于第1次基因注射后7,14d检测到IL-1Ra表达。IL-10基因治疗组对照侧和实验侧均未检测到IL-10表达。②IL-1Ra基因在兔膝关节的分布:IL-1Ra基因治疗组兔软骨表层和中间层部分细胞内表达IL-1Ra,至少持续到第1次基因注射后14d。在滑膜组织中未观察到明显的IL-1Ra表达。③兔骨关节炎软骨组织学变化:空载体对照组呈早期骨性关节炎的典型性改变。苏木精-伊红染色显示软骨细胞坏死,蛋白多糖甲苯胺蓝染色不均一,软骨表层和中间层大部分区域失染,软骨细胞簇聚区域其周围深染。IL-1Ra基因治疗组在软骨损坏方面明显减轻,甲苯胺蓝部分失染。结论:①壳聚糖-DNA超微颗粒的转染效率与基因产品有关。②将IL-1Ra用关节腔直接注射壳聚糖-DNA超微颗粒的方法直接转移入关节腔能一定程度上减轻骨性关节炎的进程。     

壳聚糖及其衍生物作为纳米药物载体的研究与应用☆◆

背景:壳聚糖由于其独特的优点在药物载体研究领域中受到越来越多的关注.目的:综述壳聚糖基纳米药物载体的体内生物效应及安全性研究,包括其药效研究、药物代谢、组织分布以及体内毒性.方法:应用计算机检索CNKI、万方数据库和PubMed数据库中1998-01/2010-05关于以壳聚糖及其衍生物为材料制备的纳米粒子和载药纳米粒子体内药效学、药代动力学和毒性试验的文章,中文以“壳聚糖”和“纳米粒子”和“体内”或“药效”或“药代动力学”或“组织分布”或“毒性”为主题词,英文以“chitosan and nanoparticle and in vivo”或“chitosan and nanoparticle and pharcodynamic or pharmacokinetic or biodistribution or toxicity”为关键词进行检索.选择文章内容与纳米粒子体内实验相关,同一领域文献则选择近期发表或发表在权威杂志文章.初检得到166篇文献,根据纳入标准选择43篇文章进行综述.结果与结论:从所检索到的文献进行总结分析,壳聚糖及其衍生物可作为蛋白类、细胞毒类和核酸类药物及诊断试剂等的载体,其载药纳米粒子与原型药物相比,显示出更长的体内循环时间、更好的药效和更小的毒副作用,体内药效和组织分布等生物效应和安全性均不同,研究方法也有所不同.     

Hydrophobically modified glycol chitosan nanoparticles as carriers for paclitaxel.

Self-assembled nanoparticles based on hydrophobically modified glycol chitosan (HGC) were prepared as a carrier for paclitaxel. HGC conjugates were prepared by chemically linking 5beta-cholanic acid to glycol chitosan chains using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. In phosphate-buffered saline (PBS; pH 7.4), the synthesized HGC conjugates formed nano-sized particles with a diameter of 200 nm and exhibited high thermodynamic stability as reflected by their low critical aggregation concentration (0.03 mg/ml). Paclitaxel was efficiently loaded into HGC nanoparticles up to 10 wt.% using a dialysis method. The paclitaxel-loaded HGC (PTX-HGC) nanoparticles were 400 nm in diameter and were stable in PBS for 10 days. These PTX-HGC nanoparticles also showed sustained release of the incorporated of paclitaxel (80% of the loaded dose was released in 8 days at 37 degrees C in PBS). Owing to sustained release, the PTX-HGC nanoparticles were less cytotoxic to B16F10 melanoma cells than free paclitaxel formulated in Cremophor EL. Injection of PTX-HGC nanoparticles into the tail vein of tumor-bearing mice prevented increases in tumor volume for 8 days. Finally, PTX was less toxic to the tumor-bearing mice when formulated in HGC nanoparticles than when formulated with Cremophor EL.     

Recent advances on biocompatible and biodegradable nanoparticles as gene carriers

ABSTRACT

Introduction: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non-viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced.

Areas covered: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes.

Expert opinion: Biocompatible and biodegradable polymers will play a necessary and important role in developing new and safe carriers for oligonucleotide delivery. More working and the development of optimized polymers will reveal more their efficacy in the treatment of patients via helping in better gene therapy.     

Novel composite core-shell nanoparticles as busulfan carriers.

This study presents a method for the design of novel composite core-shell nanoparticles able to encapsulate busulfan, a crystalline drug. They were obtained by co-precipitation of mixtures of poly(isobutylcyanoacrylate) (PIBCA) and of a diblock copolymer, poly(epsilon-caprolactone)-poly(ethylene glycol) (PCL-PEG), in different mass ratios. The nanoparticle size, morphology and surface charge were assessed. The chemical composition of the top layers was determined by X-ray photo-electron spectroscopy (XPS). (3)H-labelled busulfan was used in order to determine the drug loading efficiency and the in vitro drug release by liquid scintillation counting. Physico-chemical techniques such as Zeta potential determination and XPS analysis provided evidence about a preferential surface distribution of the PCL-PEG polymer. Therefore, composite nanoparticles have a "core-shell"-type structure, where the "core" is essentially formed by the PIBCA polymer and the "shell" by the PCL-PEG copolymer. The use of PIBCA to form the core of the nanoparticles leads to a 2-4 fold drug loading increase, in comparison to the single PCL-PEG nanoparticles. In addition, the complement activation results showed a significant difference between the composite nanoparticles and the single PIBCA nanoparticles, thus demonstrating that PEG at the surface of the nanoparticles reduced the complement consumption. The PIBCA:PCL-PEG composite nanoparticles prepared using the new co-precipitation method here described represent an original approach for busulfan administration.     

PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers.

The aim of this study was to find an effective carrier for recombinant human tumor necrosis factor-alpha (rHuTNF-alpha). The influence of solvent systems containing poly(methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) on the biological activity of rHuTNF-alpha was investigated. The PEGylated PHDCA nanoparticles loading rHuTNF-alpha were prepared with the double emulsion method. The influence of main experimental factors on the entrapment efficiency was evaluated by the Uniform Design. The physicochemical characteristics and in vitro release of rHuTNF-alpha from the nanoparticles were determined. The results showed that serum albumin such as human serum albumin (HSA) or bovine serum albumin (BSA) could play a protective action on rHuTNF-alpha in the preparation process. At > or =2.0% (w/v) HSA concentration, more than 85% of rHuTNF-alpha activity remained and the role of HSA was not affected by copolymer concentrations from 0.5 to 3.0% (w/v). The entrapment efficiency of the nanoparticles was about 60% and the nanoparticle size was about 150 nm. The nanoparticles were spherical in shape and uniform with the value of the zeta potential about -9 mV. The rHuTNF-alpha release from the nanoparticle showed an initial burst and then continued in a sustained fashion. The results showed that the PEGylated PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.     

壳聚糖以及其他生物材料作为胰岛素载体的释药性能特征

目的:探讨壳聚糖作为胰岛素载体的释药特性,展望高分子材料在胰岛素载体中的应用.方法:以胰岛素,载体,壳聚糖,脂质体,聚合物为检索词,检索中国期刊全文数据库(1999-01/2009-06);以insulin,carriers, chitosan,liposomes,polymer为检索词,检索Pubmed数据库(1999-01/2009-06),文献检索语种限制为中文和英文.以药物生物利用度、药物包埋率、药物的释放率为评价指标,纳入壳聚糖及其他生物材料作为口服胰岛素载体的研究,排除注射给药及其他给药方式的研究.结果:计算机初检得到543篇文献,根据纳入排除标准,对壳聚糖及其他生物材料作为胰岛素载体的释药特性进行分析.壳聚糖及其衍生物纳米粒作为胰岛素给药系统的研究备受关注.它在黏膜给药系统中表现出独特的纳米效应,不但可以改变药物的动力学,而且可以延长在黏膜内的滞留时间,改变膜转运机制,增加药物对膜的通透性,有效地克服了酶等生物屏障,解决了胰岛素在体内易失活及半衰期短等问题.近年来,胰岛素载体的释药性研究已经取得了一些进展,但面临的困难仍然很多,主要是包封率较低,吸收有限,而且制剂质量方法不成熟,剂量较难控制,成本较高,以及对吸收部位的损坏乃至可能对人体脏器功能带来影响.随着许多新性能高分子材料的涌现以及医药制剂工业的迅猛发展,高分子载体被越来越广泛地应用于新药的研究与开发中.结论:生物相容性、生物可降解性是选择胰岛素载药体系时需要首先考虑的问题.胰岛素载体的合成,胰岛素与载体的联接方式,间隔基对释放药物性能的影响,载体结构与单克隆抗体特异性的关系对胰岛素载体的释药性有决定性的影响.     

壳聚糖及其他生物材料作为胰岛素载体的释药性

目的:探讨壳聚糖及其他生物材料作为胰岛素载体的释药性.方法:收集1999/2008发表的关于壳聚糖及其他生物材料作为胰岛素载体的释药性及其降血糖作用的中文实验研究文献19篇,从壳聚糖胰岛素载体材料、实验方法、实验结果、实验结论方面加以整理,分别评价其释药性及降血糖作用.同时对其他生物材料胰岛素载体的类型、制备工艺、制备原理、体外释药、降血糖作用进行综合评价.结果:从15篇有关壳聚糖胰岛素载体的实验研究中选出13篇,从中可以看出部分壳聚糖胰岛素载体的释药性具有pH响应性,可根据胃肠道不同部位的pH值调节胰岛素的释放,减少口服胰岛素的胃肠道破坏;同时通过改善制备工艺如制备原料、反应时间、应用添加剂等途径可进一步改良释药性,加强胰岛素在特定部位的定位释放作用,并赋予缓释、促进药物渗透吸收等新的性能.从10篇有关其他生物材料脂质体、纳米粒、水凝胶、微球、微囊等作为胰岛素载体的实验研究中选出6篇,从中可以看出上述生物材料均具备无毒、无免疫原性、可降解、生物相容性好等特点,亦具有良好的体外释药性及降血糖作用.结论:壳聚糖及其他生物材料如脂质体、纳米粒、水凝胶、微球、微囊等作为胰岛素载体均具有良好的释药性,其临床应用具有可行性.     

5FU encapsulated polyglycerol sebacate nanoparticles as anti-cancer drug carriers

The majority of anti-cancer drugs fail to reach clinical trials due to their low water solubility. A biocompatible drug delivery system that encapsulates and efficiently delivers hydrophobic drugs to the target site is the need of the hour. This study addresses the issue by focusing on a polymeric polyglycerol sebacate (PGS) nanoparticles loaded with 5-fluorouracil (5FU), a primary line chemotherapy drug for many types of cancers. The generated nanoparticle (PGS-NP) was biocompatible and had minimal cytotoxicity against the MDA-MB-231 and A549 cell lines, even at a high concentration of 100 μg mL⁻¹. The cell viability post treatment with PGS nanoparticles encapsulated with 5FU (PGS-5FU) decreased to as low as around 40% whereas, in the case of treatment with 5FU, the viability percentage increased. The nanoparticles also showed controlled drug release when encapsulated with 5FU. This striking observation suggested that these nanoparticles can improve the efficacy of drug delivery to tumor sites. Apoptosis assay and caspase-3 activity quantification supported these data wherein PGS-5FU treatment showed almost three times caspase-3 activity as compared to control cells. Additionally, throughout all the experiments, MDA-MB-231 cells were more sensitive to PGS-5FU than A549 cells, indicating that these nanoparticles are ideal for breast cancer treatment. In summary, 5FU encapsulated PGS nanoparticles are a potential drug carrier to deliver 5FU efficiently to cancer cells.

Diagrammatic flowchart for the synthesis of polymeric PGS and preparation of 5FU-loaded PGS nanoparticles.     

壳聚糖的纳米化及其生物学效应

目的:综合分析壳聚糖纳米微粒的制备方法、研究进展及其生物学效应资料来源:应用计算机检索PUBMED 1998-01/2006-12有关壳聚糖纳米化方面的文献,检索词“Chitosan;nanoparticles”,同时计算机检索超星数字图书库2000-01/2006-12期间的相关文献,检索词为“壳聚糖”。资料选择:对资料进行初审,并查看每篇文献后的引文。选择针对性强的文章。同一领域的选择近期或权威杂志的文章。资料提炼:共收集到259篇相关文献,其中34篇符合纳入标准,排除25篇。符合纳入标准的34篇文献中,26篇涉及壳聚糖纳米粒的制备,8篇涉及纳米化后产生的生物学效应。资料综合:壳聚糖作为一类带正电的多糖,其性质不活泼,不与体液和体内组织产生免疫反应,并具有很好的生物相容性和生物可降解性。目前壳聚糖纳米化主要采用离子交联法、沉淀法、共价交联法、乳化溶剂扩散挥发法、自组装法等方法。纳米化后具有增加药物的吸收作用、增加药物的靶向性和降低药物副作用、增强药物的缓释作用及提高药物稳定性的生物学效应。结论:壳聚糖纳米粒的研究已成为当前生物医学领域的热点。纳米化后的壳聚糖在缓控释给药系统中具有广阔的应用前途,但其溶解性能有待于进一步提高。     

纳米尿激酶的性状研究

背景：尿激酶半衰期短,需持续大量给药,并发症也不小,故有必要研制具有缓释作用的溶栓药物。目的：了解包载尿激酶的水溶性壳聚糖纳米粒子的性状。方法：将壳聚糖和三聚磷酸钠以离子凝集法制备尿激酶纳米粒子后,用透射电镜观察其形态,采用粒径仪测纳米粒子粒径,酶标仪比色法测粒子包封率,纳米粒子冻干法测其载药量,并检测体内外纳米粒子缓释特性。结果与结论：当壳聚糖、三聚磷酸钠、尿激酶的质量比为7∶1∶1时,不仅溶液稳定,形成的纳米粒子粒径小,而且包封率和载药量均合适。制备出包封率最高达94.8%的尿激酶纳米粒子,载药量为14.5%,此时平均粒径236nm,透射电镜观察示粒子形态较规则,呈球形;粒子具有较好的缓释性能;表明将尿激酶包被于纳米粒子中,避免了消化酶的直接作用,延长了半衰期,不仅在体内能保持较长时间的活性,而且具有明显的缓释效果。