咖啡因对聚[碳酸(亚丙酯-co-γ-丁内酯)酯]降解性能的影响

对碱性药物与新型脂肪族聚碳酸酯———聚[碳酸(亚丙酯-co-γ-丁内酯)酯]之间的相互影响进行了研究和讨论。通过O/W单相乳化-溶剂挥发法制备了不同咖啡因含量的聚[碳酸(亚丙酯-co-γ-丁内酯)酯]载咖啡因微球。研究发现,不同的咖啡因含量影响其在聚合物中的存在状态、聚合物降解行为以及微球释药特征,但它们之间并不是简单的正比关系。咖啡因在聚合物降解过程中起着碱催化的作用。     

载万古霉素PLGA-PEG-PLGA温度敏感水凝胶的体外抗菌性能

利用聚乙二醇（PEG 1500）引发乙交酯和D,L-丙交酯开环共聚合制备聚丙交酯乙交酯（PLGA）三嵌段共聚物（PLGA-PEG-PLGA）温敏水凝胶材料,并通过核磁共振氢谱（¹H NMR）确定产物的结构及组成.应用倒置小瓶法测量得到不同浓度下PLGA-PEG-PLGA水凝胶的溶胶-凝胶相变温度为27~32℃.此外,体外降解实验及细胞毒性实验结果表明,质量分数为25%的水凝胶有满意的降解速度及良好的生物相容性.同时,利用紫外-可见光谱分析了载万古霉素水凝胶的体外药物释放行为,结果表明,万古霉素可以持续释放12 d.抗菌实验结果表明,载万古霉素水凝胶具有良好的抗菌效果.表明PLGA-PEG-PLGA三嵌段温敏水凝胶是一种较理想的万古霉素缓释载体,具有良好的临床应用前景.     

酯交换反应条件对聚(L-丙交酯-co-ε-己内酯)力学性能的影响

以辛酸亚锡催化L-丙交酯(L-LA)和ε-己内酯(ε-CL)通过酯交换反应完成本体开环聚合制得可降解的生物医用材料聚(L-丙交酯-co-ε-己内酯)(PLLCA),其结构和热性能经1H NMR,高效凝胶色谱和差示扫描量热分析表征。研究了酯交换反应条件对PLLCA力学性能的影响,结果表明,提高聚合温度有利于酯交换反应进行,L-LA和ε-CL的平均嵌段长度减小,PLLCA的玻璃化转变温度(Tg)和拉伸强度也随之减小,断裂伸长率则单调增大;增大ε-CL的投料摩尔分数同样有利于酯交换反应的进行,L-LA的平均嵌段长度随之减小而ε-CL的平均嵌段长度则增大,Tg和拉伸强度均随之减小。     

聚乳酸接枝改性纳米生物玻璃/PLGA复合材料的制备、表面性质及生物活性

以丙交酯开环聚合原位接枝改性的纳米生物玻璃(PLLA-g-BG)与聚丙交酯-乙交酯(PLGA)复合材料为研究对象, 采用TGA, ESEM和EDX分析其接枝率, 粒子分散性和表面元素分布, 通过将兔成骨细胞种植于材料膜表面进行体外培养, 采用荧光染色法、NIH Image J图像分析软件、MTT法和流式细胞术等手段检测细胞在材料表面的平均黏附数量、扩展面积比、增殖能力和细胞周期的变化, 综合评价新型改性纳米复合材料的生物相容性和生物活性. 结果表明, 聚乳酸表面接枝改性可明显改善纳米生物玻璃粒子的团聚; PLGA中掺入一定比例的改性PLLA-g-BG可明显促进兔成骨细胞的黏附、扩展与增殖; 改性纳米生物玻璃的应用可提高生物可降解聚酯材料的生物相容性和生物活性.     

三嵌段聚乳酸在溶剂中结晶驱动自组装

以端羟基聚二甲基硅氧烷(HO-PDMS-OH)为引发剂,引发L-丙交酯(L-LA)开环聚合,合成了4种三嵌段聚合物聚(L-丙交酯)-b-聚二甲基硅氧烷-b-聚(L-丙交酯)(PLLA-b-PDMS-bPLLA)。其中,聚二甲基硅氧烷(PDMS)含有74个结构单元,聚(L-丙交酯)(PLLA)的结构单元数分别是82、150、224和280。用凝胶渗透色谱仪(GPC)表征了聚合物分子量及分子量分布。将这4种三嵌段聚合物分别溶解在N,N-二甲基甲酰胺(DMF)中,在恒温水槽中静置48h,可分别组装成螺旋线聚集体以及"eye-like"聚集体。PLLA-b-PDMS-b-PLLA的组装主要由PLLA嵌段的结晶驱动。最后采用广角X射线衍射(WAXD)、透射电镜(TEM)、原子力显微镜(AFM)对聚集体进行了相关表征。     

新型PLA-PVP两亲性交联共聚物的初步研究

先以聚乙二醇(PEG)为中心嵌段,经消旋-丙交酯(D,L—LA)开环扩链,进而用丙烯酸酯封端制备了可生物降解交联剂。然后以辛酸亚锡为催化剂、甲基丙烯酸羟乙酯(HEMA)为共引发剂引发D,L—LA开环聚合,制备了末端双键功能化的大分子单体(PLA-HEMA)。最后以可降解交联剂、大分子单体和N-乙烯基吡咯烷酮(NVP)为原料,采用自由基聚合方法合成了新型可生物降解两亲性交联共聚物,并对其亲水性和力学性能进行了研究。     

载银离子PLGA-PEG-PLGA温度敏感水凝胶的制备及体外抗菌性能

利用聚乙二醇(PEG 1000)引发乙交酯和 D,L-丙交酯开环共聚合, 制备了聚丙交酯乙交酯(PLGA)三嵌段共聚物(PLGA-PEG-PLGA)温敏水凝胶材料; 利用核磁共振氢谱( ¹H NMR)确定了产物的结构及组成. 通过还原硝酸银的方法制备银纳米粒子(AgNPs), 并将其与PLGA-PEG-PLGA三嵌段共聚物水凝胶混合, 制得新型AgNPs/PLGA-PEG-PLGA复合水凝胶; 对该复合水凝胶的相关性能进行了表征. AgNPs/PLGA-PEG-PLGA复合水凝胶仍然具有温敏性能, 随着温度升高可发生溶胶-凝胶的相转变; 还可以持续释放银纳米粒子, 从而发挥抗菌性能. 体外细胞实验结果表明, AgNPs/PLGA-PEG-PLGA复合水凝胶具有良好的生物相容性, 未见明显细胞毒性, 是具有应用前景的新型复合水凝胶.     

结合分子模拟探讨PC脂肪酶催化PBS基共聚物降解的主链异构效应

采用固定化洋葱假单胞菌脂肪酶(Pseudomonas cepacia lipase,PC脂肪酶)为催化剂,在有机溶剂体系中研究了环己烷二甲醇和环己烷二甲酸对聚丁二酸丁二醇酯(PBS)的改性共聚物,即聚(丁二酸丁二醇-co-丁二酸环己烷二甲醇酯)(PBS-co-CHDMS)和聚(丁二酸丁二醇-co-环己烷二甲酸丁二醇酯)(PBS-co-BCHDA)的降解规律及其差异性.通过共聚物降解率随时间的变化、降解产物的MALDI-TOF-MS分析研究了共聚物降解规律,并以分子模拟分别研究了降解差异性和PC脂肪酶与底物的结合机制.研究结果表明,PC脂肪酶均可催化PBS基共聚物降解;在降解60 h后,相比较于PBS-co-BCHDA,PBS-co-CHDMS降解率均更大;其中PBS-co-10%CHDMS降解率最大,为85%.共聚物降解不仅生成了线型小分子,还产生了部分环状低聚物;此外,PBS-co-CHDMS降解产生的低聚物种类比PBS-co-BCHDA的要多.分子对接模拟结果表明,在氯仿中,PC脂肪酶与底物结合自由能的大小顺序为CMSCMBSCMBCABBSB,即含有丁二酸环己烷二甲醇酯(CHDMS)单元的底物与PC脂肪酶活性位点的对接更为稳定.     

功能化SEBS的制备与结构

采用熔融反应接枝的方法将(3-异氰酸酯基-4-甲基)苯氨基甲酸-2-丙烯酯(TAI)引入到聚苯乙烯-6-聚(乙烯-co-丁烯)-b-聚苯乙烯三嵌段共聚物(SEBS)上,以实现SEBS的功能化.以傅里叶红外光谱(FT-IR)、核磁共振波谱(NMR)、凝胶渗透色谱(GPC)、动态力学分析(DMA)等手段对接枝物进行了表征.研究了引发剂、单体用量对接枝率及熔体流动速率的影响.结果表明:单体TAI的自聚倾向低,已成功接枝到SEBS上,接枝后的SEBS分子量高且分子量分布宽,接枝后聚(乙烯-co-丁烯)段的玻璃化转变温度提高.     

聚肽螺旋纳米弯棒的制备与形成机理

通过五元环酸酐（NCA）开环聚合的方法成功合成了聚(γ-苄基-L-谷氨酸酯)（PBLG）聚肽均聚物和聚(γ-苄基-L-谷氨酸酯)-b-聚乙二醇（PBLG-b-PEG）聚肽嵌段共聚物，并通过酸解脱苄基及与肉桂醇的酯化反应对PBLG-b-PEG嵌段共聚物改性，制备了聚(γ-苄基-L-谷氨酸酯-co-肉桂基-L-谷氨酸酯)-b-聚乙二醇（P(BLG/CLG)-b-PEG）改性嵌段共聚物，其聚肽侧链上修饰了可光交联的肉桂酰氧基，其C=C双键在紫外光照射下能发生环加成反应交联聚肽链段。采用四氢呋喃-N,N-二甲基甲酰胺（THF-DMF）有机共溶剂溶解、选择性溶剂（水）沉淀的自组装方法制备了PBLG纳米棒；然后向纳米棒水溶液中加入THF溶剂诱导纳米棒弯曲，制备了纳米弯棒。通过THF的加入量可以调控纳米棒的弯曲程度。利用类似的方法，通过PBLG与PBLG-b-PEG或P(BLG/CLG)-b-PEG共组装制备了螺旋纳米棒（其中PBLG均聚物形成棒状内核、PBLG-b-PEG或P(BLG/CLG)-b-PEG形成表面纳米螺纹），然后向螺旋纳米棒水溶液中加入THF溶剂，但是仅得到了光滑纳米弯棒（表面螺纹...     

Preparation and characterization of hydrogels based on acryloyl end-capped four-arm star-shaped poly(ethylene glycol)-branched-oligo(<Emphasis Type="SmallCaps">l</Emphasis>-lactide) via Michael-type addition reaction

An acryloyl end-capped four-arm star-shaped poly(ethylene glycol)-branched-oligo(l-lactide) (4A-PEG-PLA) macromer was firstly prepared. A novel kind of hydrogels was synthesized via the Michael-type addition reaction between (2S,3S)-1,4-bis-sulfanylbutane-2,3-diol (dithiothreitol) and this macromer. Gelation time was determined visually as the time when the precursor solution did not flow on inverting the vials. Hydrogel structure was characterized by FTIR analysis, swelling and degradation tests. It was found that colorless and transparent hydrogels were quickly generated in situ. The gelation time, swelling and degradation behaviors of this kind of hydrogels could be adjusted by changing the concentration of the macromer solution in PBS buffer (pH 7.4). This novel hydrogel is expected to be used as a biomedical material.     

Bioactive polypeptide hydrogels modified with RGD and N-cadherin mimetic peptide promote chondrogenic differentiation of bone marrow mesenchymal stem cells

Cell-material and cell-cell interactions represent two crucial aspects of the regulation of cell behavior. In the present study, poly(L-glutamic acid)(PLG) hydrogels were prepared by catalyst-free click crosslinking via a strain-promoted azide-alkyne cycloaddition(SPAAC) reaction between azido-grafted PLG(PLG-N_3) and azadibenzocyclooctyne-grafted PLG(PLG-ADIBO).The bioactive peptides c(RGDfK) and N-cadherin mimetic peptide(N-Cad) were both conjugated to the PLG hydrogel(denoted PLG+RGD/N-Cad) in order to regulate cell-material and cell-cell interactions. Gelation time and storage modulus of the hydrogels were tunable through variations in the concentration of polypeptide precursors. The hydrogels degraded gradually in the presence of proteinases. The viability of bone marrow mesenchymal stem cells(BMSCs) was maintained when cultured with extracts of the hydrogels or encapsulated within the hydrogels. Degradation was observed within 10 weeks following the subcutaneous injection of hydrogel solution in rats, displaying excellent histocompatibility in vivo. The introduction of RGD into the PLG hydrogel promoted the adhesion of BMSCs onto the hydrogels. Moreover, when encapsulated within the PLG+RGD/NCad hydrogel, BMSCs secreted cartilage-specific matrix, in addition to chondrogenic gene and protein expression being significantly enhanced in comparison with BMSCs encapsulated in hydrogels without N-Cad modification. These findings suggest that these biodegradable, bioactive polypeptide hydrogels have great potential for use in 3D cell culture and in cartilage tissue engineering.     

通过麦克加成反应形成的三臂聚乙二醇丙烯酸酯可注射水凝胶的制备与表征

通过麦克加成反应在磷酸盐缓冲溶液中制备出一种基于三臂聚乙二醇丙烯酸酯的能快速固化的可注射水凝胶.采用倒置法测定了体系的凝胶化时间.通过红外,DMA,溶胀,降解等一系列测试,研究了该水凝胶的结构和物理化学性能.观察到通过控制前体溶液的浓度,可以控制凝胶的成胶时间和所形成凝胶的溶涨率.同时表明该水凝胶具备可注射性和可降解性.细胞毒性评价显示,该水凝胶浸提液无毒性,符合生物材料的安全评价标准.由于麦克加成反应可在人体生理条件(pH7.4,37℃)下快速进行,并且不需要任何引发剂、催化剂和有机溶剂,因此该反应非常适合应用于生物医用材料领域.     

可生物降解聚酯P(DHCA-co-LA)的合成与表征

由3,4-二羟基肉桂酸(DHCA)与D,L-乳酸(LA)经熔融缩聚法得到了新型可生物降解聚酯P(DHCA-co-LA),采用傅立叶变换红外(FTIR),核磁共振(1H-NMR)和凝胶渗透色谱(GPC)对该共聚物的组成与相对分子量进行表征,结果表明其结构明确.改变DHCA与LA单体的配比,得到的P(DHCA-co-LA)的分子量和分子量分布在同一数量级.通过差示扫描量热仪(DSC)、紫外(UV)和荧光光谱研究了共聚物的热性能、紫外与荧光性能,结果表明,P(DHCA-co-LA)有明显的玻璃化转变温度(Tg),随LA的投料比从0增加至50 mol%时,其Tg从132.26℃下降至99.12℃;当LA的投料比为20 mol%时,所得到的聚酯型共聚物溶液呈现最强的荧光强度;在紫外光照下,共聚物可进行环加成反应,但交联度总体较低;紫外光照65 min后,在荧光显微镜下观察到交联颗粒形态稳定、有较强的荧光.X-射线衍射(XRD)测定结果显示,由结晶性DHCA和LA共聚形成的P(DHCA-co-LA)为无定形聚合物,有利于生物降解.共聚物在土壤中的降解实验表明,其降解速度随体系中LA含量的增加而减缓.     

Target grafting of poly(2-(dimethylamino)ethyl methacrylate) to biodegradable block copolymers

A series of copolymers composed of methoxy poly(ethylene glycol) and a hydrophobic block of poly(ɛ-caprolactone-co-propargyl carbonate) grafted with poly(2-[dimethylamino]ethyl methacrylate) was synthesized by combining ring opening polymerization, azide-alkyne click reaction, and atom transfer radical polymerization (ATRP). Well-defined copolymers with a target composition and a tailored structure were achieved via the grafting from approach by using a single catalytic system for both click reaction and ATRP. Kinetic studies demonstrated the controlled/living character of the employed polymerization methods. The thermal properties and self-assembly in aqueous medium of the graft copolymers were dependent on their composition. The resulting polymeric materials showed low cytotoxicity toward L929 cells, demonstrating their potential for biomedical applications. This type of materials containing cationic side chains tethered to biocompatible and biodegradable segments could be the basis for promising candidates as drug and gene delivery systems.     

Rheology and Drug Release Properties of Bioresorbable Hydrogels Prepared from Polylactide/Poly(ethylene glycol) Block Copolymers

Ring-opening polymerization of L(D)-lactide was realized in the presence of poly(ethylene glycol) (PEG), yielding PLLA/PEG and PDLA/PEG block copolymers. Bioresorbable hydrogels were prepared from aqueous solutions containing both copolymers due to interactions and stereocomplexation between PLLA and PDLA blocks. The rheological properties of the hydrogels were investigated under various conditions by changing copolymer concentration, temperature, time and frequency. The hydrogels constitute a dynamic and evolutive system because of continuous formation/destruction of crosslinks and degradation. Drug release studies were performed on hydrogel systems containing bovine serum albumin (BSA). The release profiles appear almost constant with little burst effect. The release rate depends not only on gelation conditions such as time and temperature, but also on factors such as drug load, as well as molar mass and concentration of the copolymers.     

Diselenide-containing poly(ε-caprolactone)-based thermo-responsive hydrogels with oxidation and reduction-triggered degradation

Herein, novel multi-responsive injectable polyester hydrogels were reported based on the diselenide-containing poly(ε-caprolactone) copolymers ((mPEG-PCL-Se)₂). The (mPEG-PCL-Se)₂ solution remained a free-flowing state at ambient temperature but spontaneously turned into a semisolid hydrogel upon heating to physiologic temperature. The phase transition temperature was examined to be dependent on the composition and aqueous concentration of the copolymers. More importantly, the thermo-responsive hydrogels were endowed with oxidation and reduction-triggered degradation by the incorporation of diselenide groups. Accordingly, the degradation of poly(ε-caprolactone)-based hydrogels was greatly improved and the rate of degradation was well regulated by the concentration of hydrogen peroxide (H₂O₂) or glutathione (GSH). This superior stimuli-responsive degradation could lead to an enhanced drug release of encapsulated drug (Doxorubicin, DOX). Thus the oxidation and reduction-triggered degradable diselenide-containing poly(ε-caprolactone) hydrogels would offer great potential for the controlled drug delivery.     

Biodegradable polycarbonates containing side carboxyl groups—synthesis,properties, and degradation study

The main objective of the presented research was to synthesise biodegradable aliphatic polycarbonates containing reactive carboxyl pendant groups and to examine the influence of the copolymer chain microstructure and composition on the process of their hydrolytic degradation and cytocompatibility. The work describes copolymerization of cyclic trimethylene carbonate derivative containing benzyl‐ester pendant group (benzyl 5‐methyl‐2‐oxo‐1,3‐dioxane‐5‐carboxylate) with trimethylene carbonate. The copolymerization was conducted with the use of zinc (II) and lanthanum (III) acetylacetonates as ring‐opening polymerization coordination initiators. Detailed NMR analysis allowed to define the microstructure of the obtained copolymers, which depended on the composition and type of used initiator. The final tapered chain microstructure of the obtained copolymers was related to huge differences in comonomers reactivity and evidenced low level of transesterification of the main copolymer backbone. Chosen copolymers, with unprotected carbonyl groups, were subjected to in vitro degradation test and cytocompatibility studies. It was found that high concentration of carboxyl groups resulted in copolymers which formed hydrogels and were very prone to hydrolytic degradation; they were also cytotoxic toward osteoblast‐like MG 63 cells. Copolymers with lower content of carboxyl groups were found less susceptible to degradation and cytocompatible with studied cells. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2756–2769     

Injectable hydrogels as unique biomedical materials

A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.     

Lactic acid‐ and carbonate‐based crosslinked polymeric micelles for drug delivery

Our objective was to synthesize and evaluate lactic acid‐ and carbonate‐based biodegradable core‐ and core‐corona crosslinkable copolymers for anticancer drug delivery. Methoxy poly(ethylene glycol)‐b‐poly(carbonate‐co‐lactide‐co‐5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxane‐2‐one) [mPEG‐b‐P(CB‐co‐LA‐co‐MAC)] and methoxy poly(ethylene glycol)‐b‐poly(acryloyl carbonate)‐b‐poly(carbonate‐co‐lactide) [mPEG‐b‐PMAC‐b‐P(CB‐co‐LA)] copolymers were synthesized by ring‐opening polymerization of LA, CB, and MAC using mPEG as an macroinitiator and 1,8‐diazabicycloundec‐7‐ene as a catalyst. These amphiphilic copolymers which exhibited low polydispersity and critical micelle concentration values (0.8–1 mg/L) were used to prepare micelles with or without drug and stabilized by crosslinking via radical polymerization of double bonds introduced in the core and interface to improve stability. mPEG₁₁₄‐b‐P(CB₈‐co‐LA₃₅‐co‐MAC_2.5) had a higher drug encapsulation efficiency (78.72% ± 0.15%) compared to mPEG₁₁₄‐b‐PMAC_2.5‐b‐P(CB₉‐co‐LA₃₉) (20.29% ± 0.11%).¹H NMR and IR spectroscopy confirmed successful crosslinking (～70%) while light scattering and transmission electron microscopy were used to determine micelle size and morphology. Crosslinked micelles demonstrated enhanced stability against extensive dilution with aqueous solvents and in the presence of physiological simulating serum concentration. Furthermore, bicalutamide‐loaded crosslinked micelles were more potent compared to non‐crosslinked micelles in inhibiting LNCaP cell proliferation irrespective of polymer type. Finally, these results suggest crosslinked micelles to be promising drug delivery vehicles for chemotherapy. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013