壳聚糖-脱氧胆酸及其叶酸偶联体的表征及自组装特性研究

以1-乙基-(3-二甲基氨基丙基)碳酰二亚胺(EDC)为催化剂,将脱氧胆酸接枝到壳聚糖主链的氨基上,得到疏水改性的双亲性壳聚糖;再将叶酸连接于壳聚糖氨基,可得到具有肿瘤靶向潜力的双亲性共聚物.利用红外光谱、1H核磁、X射线晶体衍射图谱对其结构进行表征.脱氧胆酸-壳聚糖、叶酸-壳聚糖-脱氧胆酸在水相中通过透析处理均能形成自聚集体,利用荧光探针技术研究其自聚集行为.制得的两种自聚集体均具有较低的临界胶束浓度(10-2mg/ml),透射电镜和粒径分析测试显示制得的自聚集体为纳米级颗粒.随着脱氧胆酸取代度的增加,粒径降低,临界胶束浓度下降,但叶酸直接偶联壳聚糖导致自组装阻力增加.     

叶酸受体靶向的聚L-丙氨酸-聚乙二醇单甲醚嵌段共聚物的合成及表征

以端氨基聚乙二醇单甲醚(MPEG-NH2)为引发剂,聚合N-羧基-丙氨酸-环内酸酐(NCA)得到聚L-丙氨酸-聚乙二醇单甲醚嵌段共聚物(PLAM),并接枝叶酸,制得叶酸偶联的叶酸-聚L-丙氨酸-聚乙二醇单甲醚嵌段共聚物(FOL-PLAM).利用FT-IR、1HNMR等分析方法确认了聚合物PLAM和FOLPLAM的结构及...     

叶酸受体靶向的聚乳酸共聚物胶束的制备及性质研究

叶酸偶联的羟脯氨酸-乳酸共聚物(PLLA-PHpr-FA)是一种新型的叶酸受体靶向生物降解聚合物,研究PLLA-PHpr-FA自组装形成胶束的能力及胶束的性质。临界胶束浓度(CMC)用芘荧光探针测定,结果表明,CMC很低并依赖于乳酸/羟脯氨酸的比例。透射电子显微镜(TEM)显示共聚物胶束呈现典型的核/壳结构。动态激光光散射(DLS)测定粒径及粒径分布结果显示,粒径受乳酸/羟脯氨酸比例和丙酮量调控,但粒子几乎不受稀释的影响。用紫外分光光度法测定胶束的载药量和包封率表明,共聚物胶束对疏水性药物的包载较好。因此,PLLA-PHpr-FA胶束可以作为肿瘤靶向的药物载体。     

叶酸-聚乙二醇-聚乳酸纳米粒子的稀释稳定性和对乳腺癌细胞的靶向选择性研究

叶酸受体在实体瘤组织细胞表面的过度表达使得叶酸介导的靶向释药系统成为治疗癌症的研究热点;纳米粒子能够逃避网状巨噬细胞(RES)的捕获并加强渗透和滞留效应(EPR)是其应用于药物控释系统的主要原因。以聚乳酸、氨基封端的聚乙二醇和叶酸为原料,采用活性酯的方法合成了聚乳酸-聚乙二醇-叶酸偶合物,并以此为载体,采用溶液挥发自组装的方法制备具有主动靶向性的纳米微粒。采用1 HNMR,对材料结构进行表征;采用荧光探针法对微粒的稳定性进行检测;采用人乳腺癌细胞(MCF-7)和成纤维细胞(CCL-110)对微粒的细胞靶向选择性进行实验。结果表明,在成功合成材料的基础上,制备的纳米粒子具有很好的细胞选择性,和同类材料相比具有较好的稀释稳定性,有望成为叶酸受体介导的靶向药物控释系统的载体材料。     

叶酸靶向PAMAM载药系统在肿瘤治疗中的研究进展

综述了以叶酸(Folate)为靶向配体,聚酰胺-胺(PAMAM)为药物载体,通过叶酸受体的介导作用,实现主动靶向药物输送的研究进展;概括总结了PAMAM偶联叶酸靶向给药系统偶联药物的主要方法,并简要概括了PAMAM偶联叶酸靶向给药系统在肿瘤治疗方面及其他医学方向的研究。     

端基含SH的叶酸衍生物的合成与表征

通过三步反应制备出一种端基含SH的叶酸衍生物。首先采用双氧水作为氧化剂制备一种含羟基的二硫物;然后以二甲基亚砜为溶剂、N,N-二环己基碳二亚胺为脱水剂、4-二甲氨基吡啶为催化剂,使叶酸与二硫物发生酯化反应;最后以二硫苏糖醇作为还原剂断裂S-S键,即得到目标产物。对中间产物以及最终产物分别采用傅里叶变换红外光谱仪、紫外-可见分光光度计和核磁共振仪进行测试表征,验证了该制备过程得到了目标产物。该叶酸衍生物可以直接用于修饰纳米金属粒子,在药物输送以及靶向治疗肿瘤方面具有潜在的应用价值。     

吡咯/3-氨基苯磺酸半导体共聚物纳米颗粒的制备

采用简单的化学氧化聚合法在无外加稳定剂的条件下成功地合成了自稳定性的吡咯/3-氨基苯磺酸半导体共聚物纳米颗粒.紫外和红外光谱的分析结果证实吡咯和3-氨基苯磺酸之间确实发生了共聚.3-氨基苯磺酸投量对共聚物颗粒的产率、电导率、尺寸及分布有明显影响.当其投量为30mol％时,共聚物颗粒表现出最小的平均粒径(约80nm)和相对较高的产率及电导率.电镜表征的结果表明共聚物纳米颗粒呈现不规则的粒状形貌且尺寸分布比较均一.共聚物纳米颗粒的形成和自稳定性与颗粒表面电负性磺酸基的静电排斥效应和亲水性有关.     

端氨基聚乙二醇-聚乳酸嵌段共聚物的合成及表征

以聚乙二醇为原料,采用四步反应,合成了二碳酸二叔丁酯单保护的氨基聚乙二醇(BOC-PEG-NH2);并以DOe-PEG-NH2为引发剂,引发丙交酯开环聚合,得到了叔丁氧基酰胺基聚乙二醇-聚乳酸嵌段共聚物(BOC-PEG-PLA).在三氟乙酸二氯甲烷溶液中,脱去保护基团,得到了端氨基聚乙二醇-聚乳酸嵌段共聚物(NH2-PEG-PLA).采用核磁共振氢谱(1H-NMR)、紫外光度仪(UV)表征各聚合物的结构,由凝胶色谱仪(GPC)测定嵌段共聚物的分子量以及分子量分布.结果表明:合成的氨基引发在无催化剂条件下能够引发丙交酯开环聚合,制得分子量高、分子量分布窄的双亲性共聚物.通过三氟乙酸脱保护得到了端氨基聚乙二醇-一聚乳酸(NH2-PEG-PLA),且对分子量没有影响.     

叶酸靶向聚合物载药微粒的研究进展

介绍了叶酸靶向载药微粒的特性及其作用机制,本节就叶酸靶向药物的高分子载体进行了简要综述。重点阐述了叶酸靶向药物微粒的不同聚合物载体以及制备方法。其中针对传统方法中存在的有机溶剂残留、粒径和形貌难控制等缺点,介绍了一种绿色有效的方法—超临界抗溶剂法(SAS),并对该方法制备载药微粒的原理以及应用进行了简要概括。最后对超临界抗溶剂法制备新型叶酸-聚合物靶向载药微粒进行了展望。     

聚(乳酸-氨基酸)共聚物的合成及性能研究进展

本文详细介绍了聚(乳酸-氨基酸)线型无规共聚物、线型交替共聚物、嵌段共聚物、接枝共聚物、交联共聚物的合成路线及其性能的研究进展.在聚乳酸(PLA)大分子链中引入氨基酸(包括赖氨酸、天冬氨酸、丝氨酸、半胱氨酸等)链段后,可获得含有氨基、羧基、羟基、巯基等反应活性基团的聚(乳酸-氨基酸)共聚物.此类共聚物在保持聚乳酸良好生物相容性的基础上,还具有反应活性功能性、亲水亲脂两亲性、降解速度可控性.     

HFCVD金刚石薄膜表面的氨基修饰方法

金刚石是一种集多种优良性能于一体的功能材料,但是,金刚石薄膜sp3碳构造的高稳定性导致其表面活性不足,无法满足各种功能性表面的需要。本文从化学修饰角度,概括和总结了氨基在金刚石薄膜表面导入的一种新的简单方法,并对修饰后的金刚石表面进行了XPS表征。结果表明,氨基已成功的修饰到了金刚石薄膜表面。最后对氨基修饰后的金刚石薄膜的应用做了简单的介绍。     

聚(天冬氨酸-co-乳酸)的合成及结构与性能

由聚(琥珀酰亚胺-乳酸)的碱溶液水解反应制备了含有亲水性羧基的聚(天冬氨酸-co-乳酸)(PAL)。用IR、NMR、DSC、元素分析等方法表征了PAL的组成和结构。结果表明,PAL中的聚乳酸链段为间同立构或无规立构,由此推断丙交酯在开环聚合反应时发生了酯交换或链转移反应,导致聚乳酸链段产生消旋现象;聚合反应机理是羟基引发的聚合,获得了无定型态聚合物PAL。由于共聚反应中丙交酯熔体的蒸发损耗,合成的PAL中聚天冬氨酸的含量高于理论值。     

多壁碳纳米管的酰氯化和氨化改性及其结构表征

分别以氯化亚砜和乙二胺为改性试剂对多壁碳纳米管进行化学改性,通过红外光谱、扫描电子显微镜、热重分析和X射线衍射对制备的碳纳米管进行表征。结果表明,改性碳纳米管中含有酰氯基团和氨基基团,同时,改性使碳管长度变短,反应活性增加,但其特殊结构未受破坏。     

化学修饰制备氢键型吸附树脂

综述了酚羟基、胺基、羰基、羧基和酯基等多种化学修饰的氢键型吸附树脂的国内外研究,总结了氢键型吸附树脂中氢键吸附的主要影响因素,为合成新型氢键高分子吸附剂提供了研究思路。指出了氢键型吸附树脂目前研究中存在的问题,并提出进一步的研究方向。     

Erythrocyte folate status and serum iron levels in patients undergoing hemodialysis

The present study was aimed to evaluate erythrocyte folate and the iron levels in diabetes and hypertension patients treated with/without hemodialysis. The effects of erythropoietin and iron treatment as well as vitamin supplementation on measured parameters were considered. The 67 controls consisted of healthy subjects (n = 22), hypertensive subjects (n = 22), and diabetic subjects (n = 23) without any renal disorder. According to primary renal disorders, the patients undergoing hemodialysis (n = 68) were classified into four groups as diabetic nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial nephritis, and renal insufficiency depending on other causative factors. The mean value of erythrocyte folate levels of all patients undergoing hemodialysis was higher than the healthy control group (P < 0.05). Erythrocyte folate levels in hypertensive and diabetic nephropathy patients were higher than their own hypertensive or diabetic controls and also healthy controls (both, P < 0.05). Serum iron levels of all subgroups in hemodialysis patients were found to be similar with healthy controls (all, P > 0.05). The only significance observed within the subgroups was between diabetic controls and diabetic nephropathy patients (P < 0.05). None of the treatment or supplementation of erythropoietin, iron and vitamin affected erythrocyte folate levels (all, P > 0.05). The increase in erythrocyte folate status of patients with end stage renal diseases might be the result of sum or individual effects of causative factors such as renal pathology, compensation mechanism against renal anemia, or routine folate supplementation.     

Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent: new, ultradispersed, iron-oxide folate nanoconjugates for cancer-specific targeting

The present study describes a systematic approach towards the design and development of novel, bio-functionalized, magneto-fluorescent nanoparticles for cancer-specific targeting. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl or aldehyde groups, to be later used for bio-conjugation, were designed using an aminophosphonic acid coupling agent. These magneto-fluorescent nanoparticles were further functionalized with folic acid, using diverse conjugation strategies. A series of new iron-oxide folate nanoconjugates with excellent aqueous dispersion stability and reasonably good hydrodynamic sizes under a wide range of physiological conditions were developed. These ultradispersed nanosystems were analyzed for their physicochemical properties and cancer-cell targeting ability, facilitated by surface modification with folic acid. The nanoparticle size, charge, surface chemistry, magnetic properties and colloidal stability were extensively studied using a variety of complementary techniques. Confocal microscopy, performed with folate receptor positive human cervical HeLa cancer cells, established that these non-cytotoxic iron-oxide folate nanoconjugates were effectively internalized by the target cells through receptor-mediated endocytosis. Cell-uptake behaviors of nanoparticles, studied using magnetically activated cell sorting (MACS), clearly demonstrated that cells over-expressing the human folate receptor internalized a higher level of these nanoparticle-folate conjugates than negative control cells.     

新型生物降解交联剂的制备及其在壳聚糖交联膜中的应用

本文用聚乙二醇和丙交酯在辛酸亚锡的催化作用下合成了可降解的二羟基中间体,再与2,4-甲苯二异氰酸酯(2,4-TDI)反应,合成了异氰酸酯基封端的一系列生物降解型交联剂.并且对中间体和交联剂进行了 FTIR分析表征.应用交联剂对壳聚糖膜材料进行交联,并对交联材料进行了吸水率,表面接触角及力学性能的测定,结果表明新型生物降解交联剂的运用不仪改善了材料吸水性,也提高了材料的力学性能.     

酸碱滴定分析在聚酰胺-胺表征中的应用

整数代聚酰胺-胺(PAMAM)树形分子含有末端伯胺基及内部有叔胺基,酸碱滴定分析可以表征伯胺基及叔胺基的数量。文中详细讨论了该方法的原理,说明滴定过程中产生的酰胺键水解不影响滴定及计算结果。滴定分析在不同初始pH条件下进行,通过实验表明,在pH<2的条件下滴定可以保证叔胺的充分质子化。     

Photolithographic patterning of dendrimer monolayers and pattern-selective adsorption of linear macromolecules

Alkyl groups of n-octadecyltrimethoxysilane (ODS) in a self-assembled monolayer on a silicon substrate were oxidized to carboxyl groups by partial irradiation of vacuum ultra-violet light under the photomask, producing a COOH/ODS line pattern. After active esterification of carboxyl groups, two kinds of amine-terminated dendrimers, poly(propyleneimine) and poly(amido amine) (PAMAM) dendrimers, were immobilized on a COOH line through amide-bond so that photolithographic dendrimer/ODS pattern was finally fabricated. Preparation was certified by atomic force microscopy (AFM) and surface-enhanced infrared absorption spectroscopy at transmission mode. Adsorption of linear macromolecules was examined on PAMAM dendrimer/ODS pattern. After adsorption of poly-L-glutamic acid (PGA) at a pH below alpha-helix--random coil transition, rod-shape texture was observed only on the dendrimer line in an AFM image. This texture is an aggregate of alpha-helical PGA. Sodium hyaluronate and DNA were also adsorbed selectively on the dendrimer line, keeping the line profile, although characteristic textures were not observed.     

Self-assembled monolayer of carboxyl-terminated poly(amido amine) dendrimer

Adlayer formation and adsorption structure of 2.5th-generation poly(amido amine) dendrimer with carboxyl-terminated groups on solid substrates were investigated by atomic force microscopy, surface plasmon resonance spectroscopy, and surface enhanced infrared absorption spectroscopy. Dendrimer molecules are not uniformly adsorbed on solid surface but form aggregates with a width of approximately 100 nm and a height less than 1 nm. Adsorption reaches in equilibrium at 100-1000 sec, depending on the dendrimer concentration. The adsorption-desorption process is considerably reproducible and repeatable. Although the adsorption at equilibrium increases with dendrimer concentration and reaches maximum at neutral pH, monolayer is always maintained after the desorption with solvent. This indicates the formation of self-assembled monolayer. Such monolayer is preserved even at the variation of pH. Although most carboxylates are protonated at acidic pH, small amount of carboxylate remains even at acidic pH. The adsorption structure of dendrimer was illustrated.