叶酸修饰星型端氨基PEG-PLGA纳米胶束的制备及肿瘤细胞靶向作用

合成了星型多臂端氨基聚乙二醇(PEG)/聚乳酸-羟基乙酸(PLGA)两亲性嵌段共聚物(4s-PLGA-PEG-NH₂), 并通过核磁共振和凝胶渗滤色谱法对其结构进行表征; 采用溶剂挥发法制备阿霉素载药纳米胶束, 利用EDC缩合法与叶酸偶联, 得到叶酸修饰的星型端氨基PEG-PLGA纳米胶束; 采用动态光散射、 紫外光谱及透射电镜等手段对纳米胶束进行了表征; 对载药纳米胶束在HeLa细胞中的摄取及细胞毒性进行了初步评价. 结果表明, 经叶酸修饰的星型多臂端氨基PEG-PLGA载药纳米胶束可有效提高HeLa细胞的摄取率以及对HeLa细胞的杀伤率, 表明其可作为一类新型的靶向抗肿瘤药物递送载体.     

聚乙二醇-b-聚(D,L-丙交酯-co-碳酸丙二酯)的胶束化及其药物控释研究

通过开环共聚合成了由D,L-丙交酯、碳酸丙二酯和聚乙二醇构成的两亲性嵌段共聚物(PETLA),研究了PETLA胶束化及药物控释行为.嵌段共聚物和胶束通过核磁共振(1H-NMR)、荧光分光光度计、凝胶渗透色谱(GPC)、动态光散射(DLS)、透射电镜(TEM)和紫外光谱(UV)表征.实验结果发现临界胶束浓度随共聚物疏水链段长度增加而减小,胶束直径随疏水链段长度增加而增大.透射电镜照片表明载药胶束MT1直径为30~40nm,呈规则球形.体外释药表明9-NC以可控方式释放,突释后药物释放速率接近零级恒速.     

药物包载对两亲嵌段共聚物胶束形态的影响

以聚(ε-己内酯-b-L-丙交酯)/聚乙二醇单甲醚(P(CL-b-LLA)-b-mPEG)和聚(ε-己内酯-b-D,L-丙交酯)/聚乙二醇单甲醚(P(CL-b-DLLA)-b-mPEG)两种两亲嵌段共聚物为载体,选择了物理状态完全不同、而疏水性相近的吲哚美辛和维生素E为模型药物,研究了药物包载对高分子胶束形态的影响.发现两种药物在高分子胶束内部的增溶均会导致胶束形态发生显著改变,变化行为与胶束内核的结晶性和药物疏水性有关.另外,还研究了两种嵌段共聚物的载药性能,发现非结晶性疏水内核共聚物的药物包载率明显大于可结晶疏水内核的共聚物.     

聚乙二醇-聚乳酸共聚物药物载体

本文综述了聚乙二醇与聚乳酸共聚亲水改性的最新进展, 包括嵌段和星型结构聚乙二醇-聚乳酸共聚物(PEG-PLA)及其端基化衍生物的合成。同时概述了该共聚物以胶束、微粒、水凝胶和囊泡形式担载亲水、疏水及蛋白质类药物的应用,特别介绍了静电纺丝制备的PEG-PLA超细纤维载体及其释药特性。     

基于温敏性双亲嵌段共聚物的纳米胶束作为药物载体的研究

温度敏感性双亲嵌段共聚物由于其潜在的应用价值而引起广泛的关注。在药物控制释放领域,基于温敏性嵌段共聚物的纳米胶束作为药物载体显示了诸多特异的性能。在嵌段共聚物中引入具有温度敏感性的链段,使聚合物胶束具备天然被动靶向功能的同时,赋予了其主动靶向给药功能。本文从温度敏感性双亲嵌段共聚物的分子设计、合成、自组装性质和胶束的载药释药行为等方面进行了相关总结。重点介绍了含聚N-异丙基丙烯酰胺链段双亲嵌段共聚物的相关研究进展。     

双重敏感mPEG-PDPA-P(AAm-co-AN)聚合物自组装体的药物递送

设计合成了一种新型两亲性三嵌段ABC聚合物聚乙二醇单甲醚-聚甲基丙烯酸二异丙胺基乙酯-聚(丙烯酰胺-co-丙烯腈)(mPEG-PDPA-P(AAm-co-AN))。该聚合物具有pH敏感嵌段PDPA和温度敏感嵌段P(AAm-co-AN)，临界溶解温度(UCST)较高，且可以通过改变单体比例来调节UCST。在室温、中性环境下，该聚合物通过自组装形成刺激响应型胶束，可用于抗肿瘤药物的控释研究。温度升高诱导聚合物胶束向不对称囊泡结构转变，pH降低促使聚合物形成更加松散的胶束。在体外释药探究中，聚合物胶束对亲水药物阿霉素(DOX)和疏水药物槲皮素都具有良好的载药效果，在37℃、pH=7.4的条件下泄漏量低，随着温度升高和pH降低，胶束释放药物的速率和释放量明显增加。     

两亲嵌段聚合物载药胶束研究进展

在临床应用中,抗肿瘤药物的憎水性将严重影响疗效并造成一系列的副作用,因此,这些憎水性药物的增溶方法一直是研究的热点,其中,两亲嵌段聚合物载药胶束体系是目前最有效的方法之一,该方法通过将憎水性药物包裹在具有"核-壳"结构的纳米微球中以实现增溶目的。本文总结了目前用于载药胶束的两亲嵌段聚合物的材料及胶束的制备方法,介绍了超临界二氧化碳在此类药物胶束制备中的最新应用和该领域目前最为热门的研究方向——对肿瘤细胞具有靶向释药功能胶束的研究进展。     

肽类树枝状大分子:自组装胶束及药物释放研究

本文以三代聚谷氨酸肽类树枝状分子(G3-Glu)为大分子引发剂,引发N-羧基-L-苯丙氨酸-环内酸酐(NCA-Phe)的开环聚合反应,制备聚谷氨酸树枝状大分子-聚苯丙氨酸嵌段共聚物.嵌段共聚物通过自组装形成以聚苯丙氨酸链段为核,聚谷氨酸树枝状大分子为壳的胶束.将抗肿瘤药物阿霉素负载到高分子胶束中,研究其药物释放性能及体外抗肿瘤效果.结果表明,共聚物胶束具有良好的生物相容性.载药胶束具有药物缓释效果,药物持续释放时间可达60h.载药胶束的体外抗肿瘤实验表明其对肝癌细胞HepG2具有很好的杀灭效果,共培养48h后对癌细胞的杀死率可高达75%.     

具有pH-响应性的聚天冬氨酸类载药胶束的制备和释放能力研究

通过大分子引发剂ω-氨基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和水合肼侧基改性,制备了一系列聚乙二醇-聚氨基酸类三嵌段共聚物.其中聚氨基酸链段包括具有酰肼基的聚天冬氨酸衍生物(PAHy),以及疏水性的聚丙氨酸链段.引入具有pH响应性的腙键键合阿霉素,利用键合阿霉素与游离阿霉素之间的π-π叠合作用,在聚合物自组装形成胶束过程中通过化学键合+物理包埋的方式充分负载药物.该胶束以聚丙氨酸链段为核心,以PEG链段为冠层,以PAHy链段为包裹药物的壳层.载药胶束的粒径在170 nm左右.研究不同pH值条件下载药胶束的药物释放能力,随环境pH值的降低药物的释放速率显著增加.     

聚L-丙氨酸-聚乙二醇嵌段共聚物纳米胶束的研究

分别以氨基聚乙二醇和氨基聚乙二醇单甲醚为大分子引发剂,采用开环聚合的方法合成了两亲性聚L-丙氨酸-聚乙二醇(PAE)和聚L-丙氨酸-聚乙二醇单甲醚(PAME)两种嵌段共聚物,其结构经1H NMR,IR,DSC,GPC等表征;利用园二色技术研究了其在水溶液中的二级结构,用芘荧光探针技术研究了其胶束的形成及其临界胶束浓度(CMC),利用透射电镜研究了胶束的形态。结果表明,在水溶液中共聚物链以α-螺旋构象形式存在,在一定条件下嵌段共聚物PAE-1,PAE-2,PAME-1和PAME-2能够形成球形的稳定胶束,PAE-1形成胶束的CMC为3.36×10-5mol.L-1,CMC值受嵌段类型和共聚物中聚L-丙氨酸链段含量的影响。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

Selective syntheses of 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones via temperature-dependent Rh(II)-carbenoid-mediated 2H-azirine-ring expansion

The Rh(II)-catalyzed reaction of 2-carbonyl-substituted 2H-azirines with ethyl 2-cyano-2-diazoacetate or 2-diazo-3,3,3-trifluoropropionate provides an easy access to 2H-1,3-oxazines and 1H-pyrrol-3(2H)-ones. These compounds can be selectively prepared from the same starting material using temperature as the only varied parameter. The 2-azabuta-1,3-diene intermediate, a common precursor for both heterocyclic products, isomerizes into 2H-1,3-oxazine under kinetic control, while 1H-pyrrol-3(2H)-one is the sole product of the reaction at elevated temperatures. According to DFT-calculations a one-atom oxazine ring contraction involving ring-opening to a 2-azabuta-1,3-diene intermediate, followed by a 1,5- and 1,2-prototropic shift leads to the consecutive formation of imidoylketene and azomethine ylide, which then further undergo cyclization to the pyrrole derivative.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.