温度敏感型水凝胶

目的 综述以PNIPAm水凝胶为代表的温度敏感型水凝胶的性质及其在药学方面的应用.方法 针对目前存在的问题,阅读国内外相关文献资料,进行分析整理和归纳.结果 聚(N-异丙基丙烯酰胺)(PNIPAm)水凝胶具有一个较低临界溶解温度(LCST,33℃)或相转变温度(Ttr),具有温度敏感特性.PNIPAm水凝胶的这种特殊性能己被广泛应用在许多领域中,如药物的控制释放.结论 人们对于这类凝胶的敏感机制尚未取得共识,其在应用领域的研究尚有待于进一步的开发.     

温度敏感型水凝胶

目的综述以PNIPAm水凝胶为代表的温度敏感型水凝胶的性质及其在药学方面的应用。方法针对目前存在的问题,阅读国内外相关文献资料,进行分析整理和归纳。结果聚(N-异丙基丙烯酰胺)(PNIPAm)水凝胶具有一个较低临界溶解温度(LCST,33℃)或相转变温度(Ttr),具有温度敏感特性。PNIPAm水凝胶的这种特殊性能己被广泛应用在许多领域中,如药物的控制释放。结论人们对于这类凝胶的敏感机制尚未取得共识,其在应用领域的研究尚有待于进一步的开发。     

温度敏感性水凝胶的合成和性能研究

本文采用两种不同方法合成Ｎ－异丙基丙烯酰胺（ＮＩＰＡ）并以此单体与交联剂和引发剂等合成聚Ｎ－异丙基丙烯酰胺（ＰＮＩＰＡ）。并对凝胶性质研究，实验证明ＰＩＮＰＡ的要变温度３３℃左右，能保持物质的生理活性，在生物，医学方面有极高的利用价值。     

温敏水凝胶在智能给药系统中的应用

温敏水凝胶能随环境温度的变化而发生可逆性的体积变化，利用这种性质，将其应用于给药系统可以实现响应环境温度变化的智能化给药。在这种新型的给药系统中，温敏水凝胶可以是骨架材料，也可制成控释膜、微球、胶团等形式。本文介绍温敏水凝胶的性质以及在给药系统中的应用和释药机理。     

聚N-异丙基丙烯酰胺类温敏凝胶的制备及其对萘普生钠的缓释作用

目的：制备聚N-异丙基丙烯酰胺类的两种温敏凝胶：聚N-异丙基丙烯酰胺均聚水凝胶和N-异丙基丙烯酰胺-甲基丙烯酰胺共聚水凝胶，并考察其性质和对萘普生钠的缓释作用。方法：在氮气保护下制备两种水凝胶，测定和比较交联剂和甲基丙烯酰胺含量对凝胶溶胀度及临界相转变温度的影响。并以两种水凝胶为载体，在模拟人体肠液环境下进行萘普生钠的体外释放实验。结果和结论：交联剂用量增大时，凝胶溶胀度下降；甲基丙烯酰胺含量增加时，共聚水凝胶溶胀度增加，临界相转变温度提高。亲水性共聚水凝胶对药物的释放稳定持久，释药量大，具缓释作用。     

温敏/pH敏共聚物瓜耳胶-异丙基丙烯酰氨的制备及其水凝胶性质研究

目的:合成了新型温敏/pH敏感型高分子材料异丙基丙烯酰氨-g-瓜耳胶(PNIAAr-g-GG),并对其性质进行研究.方法:采用链引发法制备了异丙基丙烯酰氨-g-瓜耳胶共聚物,以戊二醛为交联剂制备了聚合物凝胶及其温敏游离膜,并用红外光谱与热重分析对聚合物结构进行确证;采用黏度法测定了聚合物的低温溶解温度(lower critical solution temperature,LCST);考察了离子强度对聚合物LCST的影响,温度对温敏膜药物透过性的影响,同时考察了温度、离子强度及pH值对聚合物凝胶释药的影响.结果:聚合物的LCST为37.5℃,且随溶液中离子强度的增高而线性降低;当温度高于聚合物LCST时,凝胶中药物释放速率减慢,药物经膜的透过性增加;凝胶释药速率随溶出介质中离子强度的增高而降低,随介质pH值降低而加快.结论:异丙基丙烯酰氨-g-瓜耳胶凝胶骨架片具有明显的温度敏感性及pH敏感性.     

聚丙烯酰胺凝胶隆乳术后并发症的处理

目的探讨聚丙烯酰胺凝胶隆乳的术后并发症及处理。方法对聚丙烯酰胺凝胶隆乳术后并发症165例(硬结120例、感染18例、血肿15例、破溃2例、其他10例)进行分析、分类，予以抗感染、局部穿刺抽吸、冲洗、挤压按摩等处理并随访。结果症状及体征得以改善或消除，94％达到满意效果。结论对聚丙烯酰胺凝胶隆乳术后并发症采用恰当的方法及早进行治疗可取得满意的效果，     

星点设计法优化布南色林-泊洛沙姆温敏水凝胶处方及含量测定

目的 优化泊洛沙姆温敏水凝胶体系负载布南色林,并对凝胶中布南色林含量进行测定.方法 采用直接混合法配备含药温敏水凝胶体系,倒置小管法测定胶凝温度(Tgel).以Tgel为因变量,25％泊洛沙姆407体积(X1)、50％泊洛沙姆188体积(X2)和1％布南色林药物混悬液(X3)为考察因素,通过星点设计法优化制剂处方.采用...     

甲壳素温敏水凝胶止血作用的研究

目的 评价甲壳素温敏水凝胶的止血作用。方法 制作大鼠肝脏损伤出血模型,分为空白对照组、阳性对照组、实验组,空白对照组肝脏出血创面不使用止血材料,阳性对照组、实验组肝脏出血创面分别使用纤维蛋白粘合剂和甲壳素温敏水凝胶止血,记录出血时间和出血量,于术后测定血清中TGF-β1和IL-6的含量,观察肝脏愈合情况,对损伤肝脏进行组织学观察。结果 在手术中使用甲壳素温敏水凝胶能够快速止血,大鼠术后血清中TGF-β1和IL-6含量适中,在愈合过程中炎症反应轻。     

pH及温度双重敏感性聚(N-异丙基丙烯酰胺-烯丙胺)纳米水凝胶的制备与表征

利用聚合沉淀法制备聚（N-异丙基丙烯酰胺-烯丙胺）（PNIPA-co-NH2）纳米水凝胶。考察了其粒径分布，并以500nm处的透光率表征PNIPA-co-NH2的低临界溶解温度（LCST，Tc）和pH敏感性。结果表明，通过调节表面活性剂十二烷基硫酸钠用量和烯丙胺单体的投料比可控制纳米水凝胶的粒径和Tco标记上荧光素后，PNIPA-co-NH2的紫外光谱发生明显改变。     

Injectable microsphere/hydrogel hybrid system containing heat shock protein as therapy in a murine myocardial infarction model

Abstract

Heat shock proteins, acting as molecular chaperones, protect heart muscle from ischemic injury and offer a potential approach to therapy. Here we describe preparation of an injectable form of heat shock protein 27, fused with a protein transduction domain (TAT-HSP27) and contained in a hybrid system of poly(d,l-lactic-co-glycolic acid) microsphere and alginate hydrogel. By varying the porous structure of the microspheres, the release of TAT-HSP27 from the hybrid system was sustained for two weeks in vitro. The hybrid system containing TAT-HSP27 was intramyocardially injected into a murine myocardial infarction model, and its therapeutic effect was evaluated in vivo. The sustained delivery of TAT-HSP27 substantially suppressed apoptosis in the infarcted site, and improved the ejection fraction, end-systolic volume and maximum pressure development in the heart. Local and sustained delivery of anti-apoptotic proteins such as HSP27 using a hybrid system may present a promising approach to the treatment of ischemic diseases.     

阿西美辛脂质体凝胶剂的研制

目的研制阿西美辛脂质体凝胶剂,并进行评价.方法采用不同方法、不同药-脂比处方制备脂质体,然后对其包封率进行比较,从而优选出最佳制备方法与最佳处方,并进一步制备成脂质体凝胶剂;采用HPLC测定制剂中阿西美辛的含量,葡聚糖凝胶柱结合HPLC测定制剂中阿西美辛的包封率;考察了制剂的皮肤刺激性与初步稳定性.结果制剂的含量控制在0.09%～0.110%范围之内;平均包封率为(58.76±12.47)%;无皮肤刺激性;不易高温贮存,对光不稳定.结论经初步评价,所制备的阿西美辛脂质体制备方法可行、简便、质量稳定.     

抗肿瘤药物可注射原位凝胶系统的药理学评价

中国药学会于2009年与中国学术期刊(光盘版)电子杂志社签订数字出版独家合作协议,生协议期间,中国药学会主办的科技期刊(包括天津中草药杂志社出版的4本期刊《现代药物与临床》、《中草药》、Chinese Herbal Medicines(中草药英文版)、《药物评价研究》杂志)的网络版由中国学术期刊(光盘版)电子杂志社(其出版和信息服务网站为     

Poly(D,L-lactide-co-glycolide) encapsulated poly(vinyl alcohol) hydrogel as a drug delivery system

Purpose. The efficiency of encapsulation of water-soluble drugs in biodegradable polymer is often low and occasionally these microcapsules are associated with high burst effect. The primary objective of this study is to develop a novel microencapsulation technique with high efficiency of encapsulation and low burst effect. Method. Pentamidine was used as a model drug in this study. Pentamidine/polyvinyl alcohol (PVA) hydrogel was prepared by freeze-thaw technique. Pentamidine loaded hydrogel was later microencapsulated in poly(lactide-co-glycolide) (PLGA) using solvent evaporation technique. The microcapsules were evaluated for the efficiency of encapsulation, particle size, surface morphology, thermal characteristic, and drug release. Results. Scanning Electron Microscope (SEM) studies revealed that the microcapsules were porous. The microcapsules were uniform in size and shape with the median size of the microcapsules ranging between 27 and 94 m. The samples containing 10% PLGA showed nearly three times increase in drug loading (18-53%) by increasing the hydrogel content from 0-6%. The overall drug release from the microencapsulated hydrogel, containing 3% and 6% PVA, respectively, was significantly lower than the control batches. Conclusions. The use of a crosslinked hydrogel such as PVA can significantly increase the drug loading of highly water-soluble drugs. In addition, incorporation of the PVA hydrogel significantly reduced the burst effect and overall dissolution of pentamidine.     

温敏性壳聚糖凝胶的阿霉素药物体外缓释研究

目的 壳聚糖辅以甘油磷酸钠制成温敏性凝胶，将该温敏性凝胶用作阿霉素药物栽体并观察其缓释特性。方法 制备负载阿霉素的温敏性壳聚糖凝胶，建立体外持续流动释放系统，应用紫外分光光度法测定阿霉素的含量，对该栽药凝胶进行体外的缓释实验。结果 制备了负载阿霉素的温敏性壳聚糖凝胶，并得到了其缓释曲线。结论 该温敏性凝胶能够用于负载并释放阿霉素，这为改善阿霉素使用途径提供了实验基础。     

Thermal sensitivity as a quality control attribute for biotherapeutics: The L‐asparaginase case

Thermal sensitivity, as a practical measure of thermostability, is an interesting quality attribute that can be used in the quality control (QC) release of biopharmaceuticals. This article investigates circular dichroism (CD) spectroscopy and nano‐differential scanning fluorimetry (nano‐DSF) to evaluate the thermal stability of E.coli L‐asparaginase (L‐ASNase) for QC purposes. In CD, molar ellipticity as a function of temperature (from 20 to 80°C) was measured at 222 nm. Different L‐ASNase samples dissolved in different diluents were investigated by determining the melting temperature (T_m) from the first derivative curve as well as the slope of the fitted sigmoidal function of the temperature gradient CD data. The obtained T_m values could be correlated with the L‐ASNase sample origin as well as with the pH of the diluent. The T_m values obtained from the CD data were moreover consistent with the T_m values determined by nano‐DSF, confirming their reliability. Next to the T_m value, also the slope of the fitted sigmoidal CD‐function was able to differentiate different L‐ASNase samples, including unstressed from stressed protein. By using both the T_m and the curve slope, the thermal stability of L‐ASNase was investigated, demonstrating and recommending the use of this heat‐stress characteristic as a QC quality attribute of proteins, which can be applied to detect substandard and falsified proteins.     

Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of intravenous drugs

An amphiphilic chitosan derivate, N-octyl-O-sulfate chitosan (NOSC) was prepared by octylation of amino group at C-2 position and sulfonylation at C-6 position. Micelle formed by NOSC has great capability in solubilization of water-insoluble drug paclitaxel. Enormous attention was attracted by the potential application of NOSC as a new drug delivery system. Tritium labeled NOSC (³H NOSC) was injected by tail vein at dose of 13.44 mg/kg in mice; kidney retained the maximum amount of NOSC all the time even after 24 h following the injection. Pharmacokinetic parameters (the area under the plasma concentration–time curve, maximum plasma concentration, apparent plasma half-life of distribution phase and elimination phase, mean residence time, apparent volume of distribution, total body clearance) were obtained by fluorometric method in rats. The results showed a linear pharmacokinetics proceeding of FITC-NOSC in vivo. 75.4 ± 11.6% ³H NOSC of dose was excreted in urine over a 7-day period, urinary excretion was the predominant way of excretion of NOSC compared with bilary or fecal pathway. A series of safety studies consisted of acute toxicity study, intravenous stimulation study, injection anaphylaxis study, hemolysis study and cell viability assay were performed to warrant the biocompatibility of the NOSC as intravenous materials. The LD₅₀ value of NOSC administrated by i.v. and i.p. were calculated as 102.59 and 130.53 mg/kg, respectively. No intravenous stimulation, injection anaphylaxis, hemolysis and cytotoxicity were observed in the safety studies. The tissue distribution, pharmacokinetics, excretion and safety study were persuasive for the potential application of NOSC as a new drug carrier.     

Geranylgeranylacetone protects rat and striatum neurons against heat injury via induction of Hsp70

GGA (geranylgeranylacetone) may induce Hsp70 synthesis, thus contributing to the protective effects of GGA in several disease states. This study evaluated the protective effects of GGA against heat injury to rat and striatum neurons in terms of mechanisms. Rats were exposed to 41.5 °C for 35 min to induce heatstroke; the protective effects of GGA were then evaluated by change in rectal temperature (Tre) during heat exposure and survival time after heatstroke. Primary cultured striatum neurons were incubated with GGA for 24 h, and then heat-treated at 43 °C for a further 1 h. The viability, membrane surface ultrastructure and Hsp70 expression of striatum neurons were all observed. Furthermore, the effects of quercetin an inhibitor of Hsp70 synthesis were also investigated. Compared to the heatstroke group, GGA delayed Tre in reaching 42.1 °C (P < 0.05) and prolonged the survival time after heatstroke (P < 0.01). The LDH releasing percentage decreased in GGA groups (P < 0.05, P < 0.01) compared to the heat-treatment group and increased in quercetin groups (P < 0.05) compared to GGA group. Results from AFM showed that GGA protected membrane surface ultrastructure against heat injury. In addition, results from Western blot showed that GGA-induced Hsp70 expression of neurons both in normal and heat-treatment conditions (P < 0.01, P < 0.05) and quercetin inhibited GGA-induced Hsp70 expression (P < 0.05). Therefore, GGA had protective effects against heat injury in striatum neurons and rat heatstroke. Quercetin inhibited GGA-induced Hsp70 expression and prevented GGA-protective effects, which indicated that this protection was dependent on the Hsp70 synthesis.     

嵌段共聚物OSM1-PCLA-PEG-PCLA-OSM1的pH和温度敏感性质及体外释药特性考察

目的 为嵌段共聚物磺胺甲嘧啶低聚物-聚-ε-己内酯-丙交酯-聚乙二醇-聚-ε-己内酯-丙交酯-磺胺甲嘧啶低聚物（sulfamerazine oligomers-poly(ε-caprolactone-co-DL-lactide-b-ethyleneglycol-b-ε-caprolactone-co-DL-lactide)-sulfamerazine oligomers,OSM₁-PCLA-PEG-PCLA-OSM1)作为缓控释给药系统的载体提供依据。方法 采用激光粒度仪对不同pH和温度下嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束粒径大小、分布进行考察;通过表面张力和相转变温度测定对其临界胶束浓度和溶液-凝胶相转变行为进行考察;以5-氟尿嘧啶为模型药,通过透射电镜观察载药和空白共聚物胶束形态;采用物理混合法制备5-氟尿嘧啶载药水凝胶;采用HPLC法测定载药水凝胶中药物释放速率。结果 嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁胶束溶液具有pH和温度双重敏感的性质,在一定pH和温度条件下可发生溶液-凝胶相转变;5-氟尿嘧啶载药水凝胶体外释放可持续9 d,具有较好的缓释作用。结论 pH和温度双重敏感型嵌段共聚物OSM₁-PCLA-PEG-PCLA-OSM₁作为注射缓释给药系统载体材料具有良好的应用前景。