基于天然高分子基元的阻隔层对磁性载药聚乳酸微球的控释作用

利用层层组装技术构建了基于天然高分子壳聚糖和海藻酸钠的阻隔层, 并研究了该阻隔层对磁性载药聚乳酸微球的药物释放作用. 实验结果表明, 阻隔层能够有效抑制模型药物的突释, 具有延缓药物释放的效果. 具有阻隔层的磁性载药体系具有药物释放平缓和生物相容性高等特点, 是理想的磁靶向载药体系.     

壳聚糖/丝素纳米纤维载药多层膜的构建和抗菌应用

构建抗菌表面涂层,是解决医疗器械表面因黏附生长细菌引发医源性感染的理想途径.因此,本研究利用层层自组装技术,以静电相互作用为驱动力制备了壳聚糖/丝素纳米纤维(CHI/SNF)多层膜,通过紫外-分光光度计(UV-Vis)追踪该多层膜的组装过程,并使用扫描电镜(SEM)对其进行形貌分析.然后,通过引入天然抗菌药物小檗碱(BBR)获得BBR-CHI/SNF多层膜.初步探讨了该载药多层膜的体外药物释放行为和对金黄色葡萄球菌和绿脓杆菌的抗菌性能.测试结果表明,多层膜的载药量能够通过调整膜的层数来控制.多层膜具备抗细菌黏附及一定抑菌性能,负载BBR后,通过BBR与多层膜内CHI的协同作用,抗菌性能得到了提升,抑制了金黄色葡萄球菌和绿脓杆菌的生长,其抑制率分别达到了(59.62±4.28)%和(51.65±3.77)%.总而言之,本研究构建了一种兼具抑菌和抗细菌黏附功能的载药多层膜,该多层膜制备简单,性能易于调控,基底灵活,因此在生物医用材料表面抗菌领域具有良好的应用前景.     

层状组装：先进药物控释涂层材料的新选择*

先进的药物控释体系和医用植入体是生物医用材料研究的重要内容,将两者有机结合构成的结合装置为采用药物控释的手段有效解决医用植入体面临的挑战,提升医用植入体的功能提供了新的可能。基于静电交替组装的层层组装技术具有操作简单,涂层组成、厚度可控,适用组装分子和组装基材种类广泛,利于保持药物活性等一系列优点,已成为先进药物控释涂层材料的新选择。本文从层状组装多层膜构建原位药物控释涂层的方法研究,对药物释放的调控和功能药物涂层研究三个方面对这一技术在该领域的应用进行了简要介绍。系统总结了层状组装作为先进药物控释涂层材料的优势。并针对将药物控释与医用植入体有机结合的要求,对现有层状组装涂层方法的不足和今后发展的方向进行了论述。     

聚乳酸包载5-氟尿嘧啶靶向超微粒子对人胃癌转移瘤的靶向性和控制释放研究

使用w／o／w复乳法制备聚乳酸载5-氟尿嘧啶超微粒子,使用透射电镜、激光粒度仪和紫外分光光度计对超微粒子进行表征,并考察其体外释药性质。将^99mTc标记的连有VEGF121单克隆抗体的超微粒子通过尾静脉注射到SCID裸鼠体内,观察它对胃癌转移瘤的靶向效果和治疗效果。结果显示超微粒子成圆球形,平均粒径为195.2nm,多分散系数为0.148,靶向载药超微粒子的载药率为8．23％,包封率为24．71％。聚乳酸载5-Fu超微粒子在PBS缓冲溶液中具有较好的控释效果,累积释放量Q与时间平方根t^1/2基本呈线性关系．尾静脉注射靶向超微粒子两小时以后可看到大部分超微粒子集中到肿瘤部位。在所有的实验组中,含5-Fu靶向载药超微粒子组的疗效最好,说明本靶向载药超微粒子具有抑制肿瘤的血管生成并在肿瘤组织释放化疗药物抑制肿瘤生长的双重作用。     

聚乙二醇-聚乳酸共聚物胶束溶液的冷冻干燥及胶束体外释药动力学研究

合成了一系列亲水、疏水链段质量比例不同的聚乙二醇-聚乳酸(PEG-PLA)嵌段共聚物胶束, 并以两性霉素B为模型药物制备了载药胶束. 为获得稳定性良好的、可长期储存的载药胶束剂型, 对胶束进行了冷冻干燥. 使用不同浓度的糖类(包括甘露糖、海藻糖、葡萄糖)、泊洛沙姆188 (Pluronic F68)、聚乙二醇作为冻干保护剂, 以冻干产品的重分散性、冻干前后胶束的粒径及多分散性为指标评价各种保护剂的保护效果. 结果发现, 当嵌段聚合物中聚乳酸链段的质量百分比小于或等于聚乙二醇时, 糖类、Pluronic F68和PEG均可以起到有效的冻干保护作用; 而对于聚乳酸链段质量比例较大的共聚物胶束, 只有PEG和Pluronic F68能够起到较好的冻干保护作用. 对载药胶束体外释放研究表明, 聚合物胶束的体外释放缓慢, 符合一级动力学特征.     

动态多孔海绵结构多层膜负载溶菌酶用于抗菌涂层的研究

以聚丙烯酸(PAA)和聚乙烯亚胺(PEI)为构筑单元,运用层层自组装技术制备了聚电解质多层膜.该多层膜具有独特的动态特点——经酸处理后膜内部形成海绵状通孔结构,该海绵结构在饱和水蒸气的处理下,多孔结构能够闭合,重新回到致密的膜结构.借助该种动态多层膜平台,能够简单有效地通过毛细作用力将溶菌酶负载并固定于多层膜中,为制备基于抗菌蛋白的抗菌涂层提供了新的方法.扫描电镜表征了多层膜动态变化过程,激光共聚焦显微镜表征了溶菌酶在膜内的分布情况,并测定了溶菌酶载入量及其释放动力学.进一步的抗菌测试表明该种抗菌涂层在溶菌酶和PEI的共同作用下可以有效地抑制金黄色葡萄球菌.将多层膜同时负载溶菌酶和乳铁蛋白,提升了涂层对大肠杆菌的杀菌效果.     

层层自组装膜的研究:从基础到生物医学领域中的应用

层层自组装是利用分子间的静电、氢键、共价键等相互作用将高分子组装成膜的技术,具有操作简单、无需特殊设备、膜组分及厚度可控等优点,在器件制备、表面改性及生物医学等诸多领域有广泛应用。我们在层层自组装膜的基础研究及应用领域均进行了一些探索,首次将氢键和共价键层层组装技术从二维体系扩展到三维体系,成功地制备了氢键和共价键键合的层层组装的空心微胶囊;提出了制备单一组分层层自组装膜的通用办法;对以聚乙烯基吡喏烷酮/聚丙烯酸膜为代表的氢键自组装膜进行了详细研究。首次以可逆共价键-苯硼酸酯键为驱动力进行层层组装,并在这些研究的基础上提出了动态层层自组装膜的概念。利用动态膜逐步解离的特性提出了新的药物释放方法,同时,利用层层自组装水凝胶膜的刺激响应性还提出了新的可快速响应的光学传感方法。     

交联聚乳酸中空微球的制备与表征

由于聚乳酸具有良好生物相容性与降解性,故可用作控释给药系统的载体材料．有关聚乳酸及其共聚物微球药物载体、释放行为及微球表面引入基团使之功能化的方法研究已有报道．以其它生物大分子材料作为囊壁材料的缓释微胶囊也有报道,但以聚乳酸制备中空微囊型的药物释放载体却鲜有研究．通过控制分子量、微囊大小、囊壁厚度等参数,     

一种新型的氢键自组装液晶光控取向膜

报道了一种新型的以氢键为驱动力的液晶自组装光控取向膜, 研究了薄膜的制备方法与光敏特性. 通过聚(4-乙烯基吡啶)中的吡啶基团与光敏聚丙烯酰氧基肉桂酸间的氢键作用制备了LBL(layer-by-layer)型的自组装多层膜, 制备过程的紫外-可见光谱表明, 该组装过程为逐层、均匀沉积过程. 傅里叶变换红外光谱表明, 多层膜的成膜驱动力为氢键. 用线性偏振紫外光辐照该薄膜, 多层膜中与光矢量方向匹配的光敏基团发生[2+2]环加成反应, 形成表面张力各向异性的薄膜. 用该薄膜作为向列相液晶的取向膜制成平行液晶器件, 在偏光显微镜下观察, 发现获得了均一、稳定的取向效果.     

羟基喜树碱-类水滑石纳米杂化的共组装制备及表征

采用共组装法在水溶液中制备羟基喜树碱(HCPT)-层状双金属氢氧化物(LDH)纳米杂化物.先利用微通道反应器通过共沉淀法制备了Zn₂Al-NO₃ LDH纳米片,然后与羧酸盐型HCPT在水介质中共组装,制备了HCPT插层LDH的纳米杂化物.利用酸处理,可将层间HCPT由非生物活性的羧酸盐型转化为生物活性的内酯型,这对高生物活性HCPT-LDH纳米杂化物的绿色制备具有重要意义.共组装法制备HCPT-LDH纳米杂化物,耗时短、载药量高、分散性好,且利用原料配比可方便地调控载药量. HCPT分子在LDH层间以其长轴倾斜于层板呈双层排列.所制备的HCPT-LDH纳米杂化物具有良好的药物缓释性能,颗粒内部扩散是药物释放过程的控速步骤.药物释放过程可用准二级动力学模型描述.可以用于构筑LDH基药物输送-控释体系.     

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%.     

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.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

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.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.