Ring-opening polymerization of epsilon-caprolactone and L-lactide using organic amino calcium catalyst

Poly (6-caprolactone) (PCL) and poly (L-lactide) (PLA) were prepared by ring-opening Polymerization catalyzed by organic amino calcium catalysts (Ca/PO and Ca/EO) which were prepared by reacting calcium ammoniate Ca(NH3)(6) with propylene oxide and ethylene oxide, respectively. The catalysts exhibited high activity and the ring-opening polymerization behaved a quasi-living characteristic. Based on the Fr-IR spectra and the calcium contents of the catalysts, and based on the H-1 NMR end-group analysis of the low molecular weight PCL prepared using catalysts Ca/PO and Ca/EO, it was proposed that the catalysts have the structure of NH2-Ca-O-CH(CH3)(2) and NH2-CaO-CH2CH3 for Ca/PO and Ca/EO, respectively. The ring-opening polymerization of CL and LA follows a coordination-insertion mechanism and the active site is the Ca-O bond.

Flow injection analysis of histidine with enhanced electrogenerated chemiluminescence of luminol

A simple and sensitive flow injection method is presented for the determination of histidine based on its enhancement of electrogenerated chemiluminescence (ECL) of luminol. After optimization of the experimental parameters, the working range for histidine was in 1.0 x 10(-6) to 1.0 x 10(-3) mol/L with a detection limit (S/N = 3) of 0.56 mumol/L. The relative standard deviation was 1.6% for 11 measurements of 5 x 10(-5) mol/L histidine solution. The proposed method has been successfully applied to the determination of histidine in real pharmaceutical preparation.

骨修复用纳米生物玻璃/聚乳酸复合材料的研究

本文首次制备了纳米生物玻璃左旋聚乳酸复合材料，并针对两者之间界面不相容的现象，对生物玻璃表面进行了有针对性的改性；对其纳米颗粒的分散能力进行了表征，并对复合材料的力学性能和生物相容性进行了研究，以期能得到一种具有良好力学性能和生物活性的可降解骨组织修复材料。 （1） 以正硅酸乙酯为硅源，以磷酸氢二铵为磷源，硝酸钙为钙源制备了纳米生物玻璃的凝胶颗粒(BAG, SiO2: CaO: P2O5 =37/54/9, mol/mol) ；以其表面的硅羟基为引发点，采用丙交酯开环聚合原位改性的方法对其进行了表面改性得到了改性纳米生物玻璃的凝胶颗粒（m-BAG）；通过改性，使其表面性质由亲水性变为亲油性，提高了其在聚乳酸基体内的分散能力；m-BAG/PLLA复合材料改变了改性以前BAG/PLLA力学性能随生物玻璃含量增加而不断下降的趋势，保持了聚乳酸的力学性能，在m-BAG含量为2%的时候其拉伸强度相对于纯聚乳酸提高16%左右，模量达到纯聚乳酸的1.4倍；而当m-BAG含量为10wt%，复合材料保持与纯聚乳酸相似的拉伸强度，而此时10wt%BAG/PLLA复合材料的力学性能只有纯聚乳酸的80%; 生物玻璃凝胶/聚乳酸复合材料在模拟体液中表现了较高的钙沉积能力，最后在其表面都形成了羟基磷灰石的晶体，但是表面改性使其钙沉积的速度降低，在一定程度上减小了其活性；细胞试验表明，不论生物玻璃凝胶/聚乳酸复合材料还是改性后的复合材料都表现出了很高的细胞黏附性能和增殖性能。 （2） 通过煅烧将生物玻璃的凝胶颗粒制备了生物玻璃纳米颗粒，通过XRD和TGA确定该组成类型的生物玻璃的结晶温度在826ºC，我们选择其经过600ºC煅烧的非晶态的材料作为我们进一步研究的对象。通过六次甲基异氰酸酯作为偶联剂，我们将低分子量的Mn=9,700Da的聚乳酸偶连到生物玻璃纳米颗粒的表面；通过改性提高了生物玻璃/聚乳酸的拉伸强度和拉伸模量，并提高了其分散能力；模拟体液试验表明，其复合材料具有很强的钙沉积能力，细胞培养证明了优异的生物相容性；而且通过试验可以看出，生物玻璃相对于其原始的纳米凝胶颗粒具有更优异的钙沉积能力和细胞相容性。 （3） 通过将三臂聚乳酸添加到线性聚乳酸的内部，大幅度的提高了其冲击强度，当三臂聚乳酸含量达到2wt%-8wt%时，冲击强度达到线性聚乳酸的2倍左右；通过偏光显微镜观察，可以看到三臂聚乳酸提高了线性聚乳酸的结晶成核速度，使其最后晶体数量增多，形态变小；而通过等温结晶试验表明其结晶速度提高，结晶是以异相成核的三维生长方式进行的；流变学试验表明加入三臂聚乳酸有力的降低了体系的复数粘度，当三臂聚乳酸含量达到8%时候，在频率为1-10rad/s其数值仅为线性聚乳酸的60%左右，这种变化将提高其加工成型能力。 （4） 通过十六烷基三甲基溴化铵作为模板剂，制备了具有多孔结构的生物玻璃纳米颗粒，其孔径在2nm左右，比表面积为264m2/g； 通过模拟体液试验表明，其具有很强的生物活性，规整结构在浸泡的前8小时被破坏，体系中P和Ca的含量大幅度上升，在24小时以后形成了羟基磷灰石的晶体。该类型的材料有望应用于制备药物缓释材料，用于骨修复初期的感染和炎症治疗。

可生物降解的两亲性嵌段共聚物的自聚集行为研究

可生物降解的两亲性嵌段共聚物PLA-PEG飞所制备的胶束或纳术粒子，作为潜在的药物控制释放体系弓！起人们广泛的兴趣。，方们授有寿比山于PEG链的空间位阴．效应可以避免单核噬菌体的吞噬，、并且可以通过控制可降解部分的降解行为实现药物的持续释放，使在微载体内所包载的药物分子持续释放出来。尽管高聚物的胶束和纳米粒子作为药物的胶体载体已作厂泛研究，但是对其本身物理化学性质与应用之间的联系研究甚少。因此本文对一系列PLLA和PEG两嵌段和三嵌段共聚物的自聚集行为进行了细致研究，得到了以卜结论：1．以花为"模型药物"，通过荧光探针技术对一系列两亲性共聚物在水呀招夜和NaCI溶液种的胶束化行为进行了研究。这些共聚物是由一种新型氨钙催化利，以人分J，的聚乙二醇（PEG）为引发剂，引发丙交酷开环聚合得到，，其中囚定长度阴 PEG段分剐为44，104和113环氧乙烷早兀，PLLA的长没在15-280乳酸中元之间。由于氨钙准活性的特点，这些共聚物的分散度较低，均在1.1-1.3之间。其临界胶束浓度cmc发现随PLLA的含量增加I荆氏。具有同一PEG长度的两嵌段和三嵌段共聚物cmc值的截然差别为它们胶束的构型不同提供了证据。同时也发现了NaCI的加入对丫EG段和争LLA段较短洪聚物的cmc的降低有明掀笋作用，而对具有较长PEG段或较长PLLA段的共聚物的cmc基本上没有什么影响。2．通过荧光探余十技术测定花在这一系列共聚物胶束溶液锄勺配分系数在0.2*10~5至1.9*10~5之间，对于同-PEG段的共聚物，花在其胶柬相中的配分系数随PLLA的含量的增加而增加。另外发现NaCl的加入能够促进花在胶束相中的配分。3．通过透射电子显微镜研究了两嵌段共聚物水溶液胶束的形貌，发现胶束的粒径和分散度均随PLLA段的增加而增加：通过原子力显微镜研究"这些纳米粒子退火前后的形貌变化，发现退火后纳米粒子重新自聚集为类似于神经网络红脚乏的"纳米条带"结构，其中心为类似"神经元"的团簇结构，而周困为支化的车由突"分支结构，这与文献上提到的只有三嵌段共聚物能够形成支化的"纳米条带"结构截然不同，其自聚集机理在进，步研究之中。4．以亲水性的荧光素为荧光探针研究了两嵌段共聚物在甲苯中的胶束化行为，发现其clnc值随PLLA段的含量增加而降低，相对于PEG段，PLLA段在其胶宋化过程中起主要作用。通过1HNMR证明两嵌段共聚物在甲苯中的胶束具伯以PLLA段为"核"、PEG段为"壳"的"核-壳"结构，这种胶柬化行为通过溶解度参数的差异进行了解释。5.通过原子力显微镜发现，当这些胶束滴加在云母表面上经过热处理后，这些胶束重新自聚集成为规则的具有平缓隆起的纳米结构，这与由水中得到的胶柬热处理后的形貌截然不同，并对此进行了进一步解释。由XPS分析认为主要是PEG段覆盖在PLLA段表面。

骨固定用聚乳酸/无机纳米粒子复合材料

本论文针对目前用于骨固定和骨修复的聚乳酸／无机纳米粒子复合材料的界面强度低、粒子分散不均匀以及所采用生物活性无机填料粒径较大等缺点，对轻基磷灰石及生物活性玻璃无机纳米粒子的制备、界面改性、粒子的分散、以及复合材料的制备进行了较详细的论述。另外，对材料的力学性能、结晶性能和生物相容性进行了较细统的测试和研究。（1）以磷酸和氢氧化钙为原料在40-80℃的反应条件下制备出了米粒状和棒状的HAP粒子，然后在-50℃的冷冻干燥机中干燥48h，得到白色的HAP粉末。用TEM、SEM、WAXD、FTIR等对所得产物进行了表征。研究结果表明，提高反应温度有利于生成高结晶度的长棒状HAP颗粒。此外，锻烧温度对粒子的形貌和结晶度也有很大的影响，锻烧温度越高，粒子的结晶度就越高，并且，当锻烧温度提高到900℃以上时，HAP粒子的形貌会由长棒形逐渐变成球形。（2）在高纯氢气气氛中，以辛酸亚锡为催化剂的反应条件下使左旋丙交酷开环聚合，直接接枝到HAP的表面，使HAP的粒子表面覆盖一层聚乳酸分子，使HAP的亲油性能得到提高。对表面接枝的轻基磷灰石（g-HAP）用31PMAS-NMR、FTIR、TGA、TEM、SEM和GPC进行了表征。结果表明，用此方法可在HAP表面接枝6％的PLLA。（3）用溶剂法制备了PLLA/g-HAP复合材料，并对其机械性能、结晶性能和生物相容性进行了表征。试验结果表明：与纯HAP相比，g-HAP粒子更容易均匀分散到PLLA基体中，当填料含量达到4％时，PLLAg-HAP复合材料的力学性能达到最好。由Dsc和PoM的实验结果表明，g-HAP粒子在聚合物基体中可以起到异相成核剂的作用。细胞实验结果表明，PLL刀g-HAP复合材料的细胞相容性明显优于纯的PLLA和PLLA/HAP复合材料。（4）以正硅酸乙酷（TEOS）、硝酸钙（Ca(NO3）2）和磷酸氢二按（（NH4）ZHPO4）为原料，利用在酸性溶液中水解，碱性溶液中缩聚沉淀，然后将反应液离心分离，冷冻干燥，最后在马弗炉中锻烧的方法，得到白色的5102-coo-PZos三元生物活性玻璃粉末。SEM和TEM分析结果表明，所得到生物活性玻璃是粒径在40nln左右的球形颗粒，且粒径分布非常均匀。（5）以正硅酸乙酷（TEoS）和硝酸钙（Ca（NO3）2）为原料，利用在酸性溶液中水解，碱性溶液中缩聚沉淀，然后将反应液离心分离，冷冻干燥，最后在马弗炉中锻烧的方法，得到粒径为200nm左右的球形SiO2-CaO二元生物活性玻璃粉末。

PEGylated Phospholipid Membrane on Polymer Cushion and Its Interaction with Cholesterol

By employing poly(ethylene glycol) (PEG) shielding and a polymer cushion to achieve air stability of the lipid membrane, we have analyzed PEG influence on dried membranes and the interaction with cholesterol. Small unilamellar vesicles (SUVs) formed by the mixture of 1,2-dimyristoylphosphatidylcholine (DMPC) with different molar fraction of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000)) adsorb and fuse into membranes on different polymer-modified silicon dioxide surfaces, including chitosan, poly(L-lysine) (PLL), and hyaluronic acid, Dried membranes arc further examined by ellipsometer and atomic force microscopy (AFM). Only chitosan can support a visible and uniform lipid array. The thickness of dry PEGylated lipid membrane is reduced gradually as the molar fraction of PEG increases. AFM scanning confirms the lipid membrane stacking for vesicles containing low PEG, and only a proper amount of PEG can maintain a single lipid hi lover; however, the air stability of the membrane will be destroyed if overloading. PEG. Cholesterol incorporation can greatly improve the structural stability of lipid membrane, especially for those containing high molar fraction of PEG. Different amounts of cholesterol influence the thickness and surface morphology of dried membrane.

Layer-by-layer assembly of gelatin

Electrostatic assembly of one species can be realized using gelatin as a polyampholyte. Under suitable conditions where the electrostatic attraction and repulsion were both significant and in balance, linear growth of multilayers driven by electrostatic interactions was sustained over many successive assembly steps, and the maximum amount of adsorption of each layer was reached when the solution pH was around the isoelectric point. The rearrangement of the adsorbed chains after drying was confirmed by contact angle analysis. In addition with only one species involved, the assembled thin films should be chemically uniform rather than layered.

Construction of hollow DNA/PLL microcapsule as a dual carrier for controlled delivery of DNA and drug

DNA/poly-L-lysine (PLL) capsules were constructed through a layer-by-layer (LbL) self-assembly of DNA and PLL on CaCO3 microparticles, and then used as dual carriers for DNA and drug after dissolution of carbonate cores. The permeability of DNA/PLL microcapsules was investigated with fluorescence probes with different molecular weights by confocal microscopy. The result revealed that the fluorescence probes were able to penetrate the capsule walls even its molecular weight up to 150 kDa. The resultant capsules were used to load drug model molecules-fluorescein isothiocyanate (FITC)-dextran (4 kDa) via spontaneous deposition mechanism.

Preparation and application of single polyelectrolyte microcapsules possessing tunable autofluorescent properties

Autofluorescent single polyelectrolyte microcapsules, exemplified by poly-L-lysine (PLL), have been prepared through glutaraldehyde-mediated covalent layer-by-layer (LbL) assembly and subsequent core removal. CaCO3 microparticles were used as template cores for the LbL deposition and removed by treatment of ethylenediamine tetraacetic acid disodium salt (EDTA). The prepared microcapsules, without conjugating an exterior fluorochrome, exhibited evenly distributed fluorescence.

Biodegradable amphiphilic block copolymers bearing protected hydroxyl groups: Synthesis and characterization

A new biodegradable amphiphilic block copolymer, poly(ethylene glycol)-b-poly(L-factide-co-9-phenyl-2,4,8, 10-tetraoxaspiro[5,5]undecan-3-one) [PEG-b-P(LA-co-PTO)], was successfully prepared by ring-opening polymerization (ROP) Of L-lactide (LA) and functionalized carbonate monomer 9-phenyl-2,4,8,10-tetraozaspiro[5,5]undecan-3-one (PTO) in the presence of monohydroxyl poly(ethylene glycol) as macroinitiator using Sn(Oct)(2) as catalyst. NMR, FT-IR, and GPC studies confirmed the copolymer structure.

Synthesis of biodegradable and electroactive multiblock polylactide and aniline pentamer copolymer for tissue engineering applications

To obtain one biodegradable and electroactive polymer as the scaffold for tissue engineering, the multiblock copolymer PLAAP was designed and synthesized with the condensation polymerization of hydroxyl-capped poly(L-lactide) (PLA) and carboxyl-capped aniline pentamer (AP). The PLAAP copolymer exhibited excellent electroactivity, solubility, and biodegradability. At the same time, as one scaffold material, PLAAP copolymer possesses certain mechanical properties with the tensile strength of 3 MPa, tensile Young 's modulus of 32 MPa, and breaking elongation rate of 95%.

Novel pH- and temperature-responsive block copolymers with tunable pH-responsive range

A series of novel pH- and temperature-responsive diblock copolymers composed of poly(N-isopropylacrylamide) (PNIPAM) and poly[(L-glutamic acid)-co-(gamma-benzyl L-glutamate)] [P(GA-co-BLG)] were prepared. The influence of hydrophobic benzyl groups on the phase transition of the copolymers was studied for the first time. With increasing BLG content in P(GA-co-BLG) block, the thermal phase transition of the diblock copolymer became sharper at a designated pH and the critical curve of phase diagram of the diblock copolymer shifted to a higher pH region.

The release behavior of doxorubicin hydrochloride from medicated fibers prepared by emulsion-electrospinning

The release behavior of a water-soluble small molecule drug from the drug-loaded nanofibers prepared by emulsion-electrospinning was investigated. Doxorubicin hydrochloride (Dox), a water-soluble anticancer agent, was used as the model drug. The laser scanning confocal microscopic images indicated that the drug was well incorporated into amphiphilic poly(ethylene glycol)-poly(L-lactic acid) (PEG-PLA) diblock copolymer nanofibers, forming "core-sheath" structured drug-loaded nanofibers.

Hollow DNA/PLL microcapsules with tunable degradation property as efficient dual drug delivery vehicles by alpha-chymotrypsin degradation

Hollow deoxyribonucleic acid (DNA)/poly-L-lysine (PLL) capsules were successfully fabricated through a layer-by-layer (LbL) self-assembly of DNA and PLL on porous CaCO3 microparticles, followed by removal of templates with ethylenediamine tetraacetic acid disodium salt (EDTA). The enzymatic degradation of the capsules in the presence of alpha-chymotrypsin was explored. The higher the enzyme concentration, the higher is the degradation rate of hollow capsules. in addition, glutaric dialdehyde (GA) cross-linking was found to be another way to manipulate degradation rate of hollow capsules.

A facile pathway to prepare enzymatically degradable microcapsules with tunable capsule shell properties

Dextran sulfate (DS)/poly-L-lysine (PLL) microcapsules are fabricated by an in situ coacervation method using DS-doped CaCO3 microparticles as templates. Twinned superstructures or spherical CaCO3 microparticles are produced depending on DS concentration in the starting Solution. DS/PLL microcapsules with ellipsoidal or spherical outline are obtained after removal of templates in disodium ethylene diamine tetraacetate dehydrate (EDTA) without PLL. Their shell thickness and negative surface charges increase with the DS weight percentage in the templates. The surface potential of DS/PLL microcapsules.