PPEGMEA-g-PMAA全亲水接枝共聚物包埋甲氨喋呤体外控释的研究

以全亲水接枝共聚物PPEGMEA-g-PMAA为载体材料,以甲氨喋呤(MTX)为模型药物,通过物理包埋和化学键合法制备MTX药物缓释体系,探讨了pH值、制备方法等对载药量、包埋率和释药行为等的影响,两种体系均可以通过改变pH值来控制药物的释放和释放速率。     

PtBA-g-PPEGMEMA接枝共聚物的合成及其包埋阿霉素的研究

通过可逆加成-裂解链转移聚合和原子转移自由基聚合,制备了以聚丙烯酸叔丁酯为主链、以聚(聚乙二醇单甲醚甲基丙烯酸酯)为侧链的两亲性接枝共聚物PtBA-g-PPEGMEMA,该方法克服了以往通过聚合物修饰来引入接枝点时所存在的接枝点密度不高和不可控的局限性.接着,以PtBA-g-PPEGMEMA为载体,对抗肿瘤药物阿霉素进行了负载,制备得到了尺寸为164.8nm的纳米载药胶束.其释放试验表明,该体系具有缓释特征.     

多孔球状淀粉接枝共聚物的合成及其性质研究

报道了一种多孔球状淀粉接枝共聚物的合成。此球有很强的机械性能，良好的稳定性和较高的致孔率，平均孔径约为１９．５ｎｍ，以其为载体固定化糖化酶活力为１４６２ＩＵ／ｇ干胶，比活为２９．３１ＩＵ／ｍｇ蛋白。     

阴离子型含氟两亲接枝共聚物的合成及其胶束化行为研究

以聚乙二醇甲醚甲基丙烯酸酯(MPEGMA)为大分子单体,甲基丙烯酸六氟丁酯(HFMA)、对苯乙烯磺酸钠(NaSS)为共聚单体,采用大分子单体接枝共聚法,制备了一种阴离子型含氟两亲接枝共聚物P( HFMA-co-NaSS) -g-PEG.利用FTIR、1H-NMR和19F-NMR对共聚物的分子结构进行了表征.表面张力法测...     

聚硅氧烷-聚醚接枝共聚物的合成及其碱金属盐络合物离子电导的研究

 本文采用环氧乙烷与环氧丙烷共聚合成了一系列低分子量的聚醚(PEP),并用PEP的单烯丙基醚借助氢化硅烷基化反应(Hydrosilylation)制备出一种新型聚硅氧烷接枝聚醚的高分子电解质主体材料(PAEPS).分别讨论了共聚物组成、盐的种类和浓度等因素对交联PAEPS与碱金属盐络合物电解质膜离子电导的影响.结果表明,PAEPS与碱金属盐络合物的室温电导率较纯线型PEO提高两至三个数量级,电导率随温度变化关系基本上符合VTF方程,属于典型的非晶电解质行为.     

聚苯乙烯-甲基丙烯酸甲酯接枝共聚物的合成和表征

<正> 聚苯乙烯(PS)和聚甲基丙烯酸甲酯(PMMA)都是研究得十分深入的聚合物。它们的接枝共聚物,虽然在基础研究中是十分有兴趣的对象,但因传统的合成方法不能得到结构确定的产物,同时难于与伴生的均聚物分离,进展不大。近年来随着大分子单体方法和极性单体活性阴离子聚合的发展,具有确定结构的接枝共聚物PS-g-PMMA的合成逐步成为可能。例如:Ishizu采用阴离子聚合合成带乙烯基的PMMA大分子单体,再与苯乙烯自由基共聚的路线,Ballegoole等和Watanable分别采用主干接枝法,即用自     

聚肽接枝共聚物的自组装行为研究

Polymeric micelles of poly(γ-benzyl L-glutamate)(PBLG)-poly(ethylene oxide)(PEO) graft copolymer were prepared by the dialysis method in deionized water. Fluorescence spectroscopy, nuclear magnetic resonance(NMR) and transmission electron microscope(TEM) were used for the investigation of the self-assembly of PBLG-PEO graft copolymer. Fluorescence spectrosco0y measurements suggest that PBLG-PEO graft copolymer associates to form polymeric micelles in water. ^1H NMR measurements further prove that in aqueous medium PBLG-PEO graft copolymer could assemble into polymeric micelles with PBLG segments as the hydrophobic inner core and PEO segments as the hydrophilic shell. The results of the TEM observations show that the polymeric micelles of PBLG-PEO graft copolymer are almost spindly shaped, which are different from the morphology of the spherical micelles formed by PBLG-PEO block copolymer. Polymeric micelles formed by polypeptide copolymer have potential application as drug carrier in controlled-release delivery system.     

聚丙烯酰胺/聚L-谷氨酸苄酯接枝共聚物的合成及其胶束制备

以聚丙烯酰胺(PAM)为大分子引发剂, 采用开环聚合方法, 在N,N-二甲基甲酰胺(DMF)中引发L-谷氨酸苄酯环内酸酐(BLG-NCA)聚合合成了两亲性聚丙烯酰胺/聚L-谷氨酸苄酯接枝共聚物(PAM-g-BLG), 采用IR, 1H NMR和GPC方法对共聚物结构进行了表征; 用芘作荧光探针, 研究了共聚物胶束的形成及其临界胶束浓度(cmc), 利用动态光散射(DLS)和透射电镜(TEM)研究了胶束的粒径分布和形态. 结果表明, PAM能够引发BLG-NCA开环聚合得到接枝共聚物, 在一定条件下接枝共聚物能够形成球形的稳定胶束, cmc值和胶束粒径随着共聚物中疏水性聚L-谷氨酸苄酯(PBLG)链段含量的增加而减小.     

两性纤维素接枝共聚物的研究：Ⅰ,两性共聚物的合成

用过硫酸铵和四甲基车胺氧化还原引发体系合成了羧甲基纤维素接枝甲基丙烯酸二甲胺基乙酯两性共聚物（ＣＧＤ）,研究了反应温度、ｐｈ、原料羧甲基取代度,引发剂用量,反应物料配比和外加盐对接枝共聚的影响,并用红外光谱对技枝共聚物结构进行了鉴定。     

梯度共聚物接枝纳米粒子的合成及其力学性能

通过RAFT聚合制备了3种不同序列(无规、嵌段及梯度)的丙烯酸正丁酯(BA)/甲基丙烯酸甲酯(MMA)二元共聚物(PBA-r-PMMA、PBA-b-PMMA、PBA-g-PMMA),以及2种含可交联侧链的聚甲基丙烯酸酰氧基丙基三乙氧基硅烷(PTEPM)的三元共聚物PTEPM-b-(PBA-g-PMMA)和PTEPM-b-(PBA-r-PMMA),三元共聚物中PBA/PMMA分别为无规和梯度结构.这5个共聚物中PBA/PMMA段具有相近的分子量和组分比.三元共聚物通过共组装及交联后得到球状的共聚物接枝纳米粒子NP-(PBA-g-PMMA)和NP-g-(PBA-rPMMA). DSC结果表明NP-(PBA-g-PMMA)和PBA-g-PMMA具有较宽的玻璃化转变温度区间(～130℃),证明成功合成了梯度共聚物和接枝梯度共聚物的纳米粒子.通过DMA测试和变温拉伸测试发现,在升温过程中梯度结构二元共聚物及其对应的纳米复合材料力学性能呈现渐进式变化,而无规或嵌段对应物力学性能呈现突变,原因是前者具有较宽的玻璃化转变过程.由于无机内核的作用,NP-(PBA-g-PMMA)和NP-(PBA-r-PM...     

聚环氧乙烷-g-聚己内酯两亲性接枝共聚物的合成及药物释放行为

通过环氧丙醇(GL)与环氧乙烷(EO)的阴离子顺序开环聚合制备了水溶性嵌段共聚物PEO-b-PGL, 以PGL嵌段每个重复单元的侧羟基为引发点进一步引发ε-己内酯(CL)的开环聚合, 合成了结构规整的以聚环氧乙烷(PEO)为主链的两亲性接枝共聚物(PEO-b-PGL-g-PCL). 研究了PEO-b-PGL-g-PCL在水相中的自组装行为, 采用稳态荧光探针法测定了胶束的临界胶束浓度(cmc). 以疏水性药物阿霉素(DOX)为模型药物, 研究了两亲性接枝共聚物的化学组成对药物的扩散释放以及降解释放行为的影响.     

Synthesis,Characterization and Aqueous Solution Behavior of a pH-responsive Double Hydrophilic Block Copolymer

The pH-responsive double hydrophilic block copolymer poly(ethylene glycol)-b-poly(methacylic acid-co-4-vinyl benzylamine hydrochloride salt) (PEG-b-PMAA/PVBAHS) was synthesized. A series of PEG-b-PMAA/PVBAHS with different molecule weights and compositions were characterized by IR, ¹H-NMR, elemental analysis and TGA. With different MAA/VBAHS ratio, the PEG-b-PMAA/PVBAHS copolymers had the different isoelectric point (IEP). Supermolecular structures of the block copolymers could be formed by the interionic interactions at different solution pH. Experiment results showed that the structures of the pH-responsive copolymers in aqueous solution could be changed at different pH environments. The aggregation of this double hydrophilic block copolymer in aqueous solution was determined by both of solution pH and copolymer composition.     

多响应性聚肽共混胶束的药物控释性能

合成了聚(L-谷氨酸)-b-聚氧化丙烯-b-聚(L-谷氨酸)(PLGA-b-PPO-b-PLGA)三嵌段聚肽共聚物.通过透射电镜、激光光散射与核磁共振等方法研究了其与聚乙二醇-6-聚氧化丙烯(PEG-b-PPO)两嵌段共聚物共混体系的自组装行为,使用紫外分光光度计探讨了负载阿霉素的共混聚集体在不同环境下的释药行为.结果表明:该体系形成了以PPO为内核,PLGA和PEG为壳的共混胶束,该共混胶束的释药行为不仅具有pH和温度的响应性,并且对共混胶束的组分具有依赖性.     

The Cyclodextrins as Modelling Agents of Drug Controlled Release

The controlled release of nicardipine (NC) was achieved by hybridizing its hydrophilic and hydrophobic cyclodextrin (CDs) complexes, i.e., those with hydroxypropyl--cyclodextrin (HPCD) andtriacetyl--cyclodextrin (TACD),respectively. ¹H-nuclearmagnetic resonance (¹H-NMR) was performed to examine the interaction between both CDs and NC in solution. The solid complexes of NC : HPCD and NC : TACD were prepared, in a 1 : 1 molar ratio by the spray-drying method. Complexation in the solid state was demonstrated by differential scanning calorimetry (DSC) and powder X-ray diffractometry. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the USP basket method. The ¹H-NMR studies provided clear evidence of an interaction between the CDs and the aromatic rings of NC. The DSC thermograms of the solid complexes showed no endothermic peak due to NC melting and their diffraction pattern was completely diffuse, which suggested the formation of a novel type solid phase with an amorphous character. The low dissolution rate of NC, a weak basic drug, in alkaline medium was significantly improved by complexation with HPCD. In contrast, the in vitro release of this drug from the NC : TACD complexes was markedly retarded in both dissolution media. An optimal formulation was then designed by the combination, in different molar ratios, of these two complexes. The release behavior of these preparations was investigated and it was observed that the retarding effect was dependent on the amount of the NC : TACD complex. In addition, the initial release rate became faster as the molar ratio of the NC : HPCD complex increased.     

Preparation and Application of Double Hydrophilic Block Copolymer Particles

The preparation of some unique block copolymers and block copolymer particles via radical heterophase polymerization is described. Special emphasis is placed on double hydrophilic block copolymers such as poly(styrene sulfonic acid)-b-poly(methacrylic acid) diblock copolymer and double hydrophilic block copolymer particles consisting of both hydrophilic shells and cross-linked hydrophilic cores. Examples are given for the application of such particles as adsorbents, nano-reactors for chemical synthesis, and as colloidal stabilizers in both heterophase polymerization and biomineralization reactions.     

两亲性接枝共聚物在选择性溶剂中自组装行为的模拟研究

利用粗粒化分子动力学(CGMD)方法研究了两亲性接枝共聚物在不同选择性溶剂中的自组装行为. 分析了主链刚性及链长对自组装结构的影响. 研究结果表明, 当溶剂对主链为良溶剂而对支链为不良溶剂时, 两亲性接枝共聚物随主链刚性的增加自组装形成花状胶束、 花桥状胶束及桥状胶束, 并且组分比例对自组装结构影响很大; 随着链长的增加, 柔性链出现单花状胶束到多花状胶束的转化. 当溶剂对主链为不良溶剂而对支链为良溶剂时, 可得到近球形或椭球形核壳状胶束及束状结构; 不同链长时, 柔性接枝共聚物链均只能得到近球形的单核壳状胶束.     

荧光标记pH敏感胶束的制备及其药物控释

利用原子转移自由基聚合方法（ATRP）合成了pH敏感的两亲性嵌段共聚物mPEG-b-PDPA_n（聚合度n=100-200）及荧光修饰的嵌段聚合物异硫氰酸荧光素-聚乙二醇-聚N,N-二异丙胺基甲基丙烯酸乙酯（FITCPEG₄₅-PDPA₁₀₀）。采用溶剂挥发的方法制备胶束,此胶束呈现均一的球形分布,平均粒径180-240 nm（0.3 mg·mL^-1）。以阿霉素（DOX）为模拟药物,其胶束载药量约11%（w,质量分数）左右,外环境pH对载药胶束的粒径和体外释放行为有显著影响。在弱酸环境下,胶束核质子化发生膨胀甚至解体,在2-3 h内药物可释放80%左右。体外毒性试验表明,空白胶束与人类肝癌细胞（Huh7）有良好的生物相容性。同时,与此细胞共同孵育5 h的荧光聚合物胶束体现了较好的转染效果。因此,这类荧光标记胶束可能会为实时跟踪化疗药物的输送或分布打开新的视角。     

Fabrication of Reduction‐Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release

The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction‐sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction‐sensitive amphiphilic cyclic brush copolymer, poly(2‐hydroxyethyl methacrylate‐g‐poly(ε‐caprolactone)‐disulfide link‐poly(oligoethyleneglycol methacrylate)) (P(HEMA‐g‐PCL‐SS‐POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a “grafting from” approach using sequential ring‐opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self‐assembled unimolecular core–shell–corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction‐insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.