壳聚糖修饰PLGA阳离子型纳米微球的制备与表征

采用单乳化-溶剂(O/W)挥发技术制备表面带正电荷的壳聚糖(CHS)修饰聚乙/丙交酯(PLGA)纳米微球(PLGA/CHS), 通过正交试验优化了纳米微球的制备条件. 结果表明, 微球粒径可控制在150～200 nm内, 在pH=4时, 纳米微球表面电位最高为55 mV. 影响微球粒径的主要因素是聚合物的浓度, CHS的分子量和浓度以及介质的pH值对微球表面电位也有明显影响. 制备粒径较小而表面电位较高的PLGA/CHS纳米微球条件为: ρ(CHS)=3 mg/mL, ρ(PLGA)=10 mg/mL, Vo/Va=1/4. SEM图像显示经CHS修饰的PLGA的纳米微球形状规整, 荧光显微观察和XPS分析结果证实CHS包覆于微球表面.     

聚右旋丙交酯和聚左旋丙交酯乙交酯的制备及其共混物的结晶行为

以辛酸亚锡为催化剂,十八醇为引发剂,分别以右旋丙交酯和左旋丙交酯与乙交酯为原料,在真空条件下经本体熔融开环聚合制备了系列右旋丙交酯聚合物(E)和左旋丙交酯乙交酯共聚物(F),其结构经1H NMR和IR表征。利用DSC研究了E和F共混物(M)的结晶性能,结果表明,E和F能形成具有较高熔点的立构复合物(SC),其形成能力随E分子量的增加而降低,且SC的含量在E和F共混比为49∶51附近出现极大值。     

低热-高压法制备PLGA多孔支架及其体外降解研究

采用低热-高压法制备了聚(dl-丙交酯／乙交酯)75／25(PLGA75／25)组织工程多孔支架。该方法避免了使用有机溶剂，支架的孔隙率在90％以上，孔径大小分布均匀。多孔支架经过酒精处理后，支架表面产生许多微小的凹陷；用藻酸钙改性处理后，支架形态保持良好。两种处理都使支架的压缩强度有所增大，亲水性增强。虽然孔隙率高的支架降解速率稍慢，但其体外降解规律基本一致：特性粘数争力学强度衰减快，而质量损失较慢，降解6周后，支架的质量损失仅为3％左右；体外降解3周后，支架的形态保持良好，可望在细胞移植争组织修复的早期发挥支撑作用。     

乙交酯、L-丙交酯均聚物及其共聚物的制备和性能研究

以辛酸亚锡为催化剂、1,4-丁二醇为引发剂,在高温、高真空条件下本体熔融开环聚合制备了聚乙交酯(PGA)、聚L-丙交酯(PLLA)及其不同比例的共聚物(PLGA).通过红外光谱(IR)、核磁共振(1H-NMR)对聚合物的结构进行了表征,用乌氏黏度计、凝胶渗透色谱仪(GPC)、示差扫描量热仪(DSC)、热重分析仪(TGA)、X射线粉末衍射仪(XRD)、流变仪等对聚合物的特性黏数、分子量与分子量分布、热性能、结晶性、流变性能进行了研究.结果表明PLGA和PLLA具有较高的分子量和窄的分子量分布;PGA、PLLA、PLGA均具有较高的热稳定性,随着PLGA中PGA单元的增加,分解温度逐渐升高.直接熔融合成的PGA在各有机溶剂中溶解性都不理想,用二甲基亚砜(DMSO)重结晶后的PGA在六氟异丙醇(HFIP)中的溶解度增大;PGA、PLLA具有较高的结晶度,而PLGA以非晶态存在,DMSO重结晶后的PGA的结晶度降低.PGA、PLLA、PLGA的熔体均是剪切变稀流体,但PGA、PLLA具有较高的储能模量,PLGA具有较高的损耗模量.相对于PGA和PLLA,无规共聚的PLGA易纯化,并且柔性较好,更易加工,因此PLGA是更适宜的生物可降解材料.     

乙酰基丙酮络合物催化合成聚乳酸

以钕、钇、锌、铁、钴、镍六种乙酰基丙酮盐Ｍ（ＡｃＡｃ）ｎ成功地催化丙交酯开环聚合成聚乳酸。详细研究了上述乙酰基丙酮盐催化剂品种及其与单体摩尔比［Ｍ（ＡｃＡｃ）ｎ］／［ＬＡ］、温度和时间对聚合反应的影响。结果表明，使用这些催化剂都能得到高于９０％的高聚合转化率；而稀土催化剂在聚合转化率和聚乳酸分子量方面，均显示更好的催化性能；过高的聚合温度和过长的聚合时间会导致聚乳酸的分子量下降。Ｘ－衍射研究表明，以Ｎｄ（ＡｃＡｃ）３催化合成的聚乳酸为非晶聚合物。     

水蒸汽辅助法制备PLLGA蜂窝状多孔膜

以疏水性高分子L-丙交酯-乙交酯共聚物（PLLGA）为膜材质,以十二烷基硫酸钠为添加剂,在高湿度气氛环境中使用浇铸成膜的方法制得了具有规整蜂窝状结构的薄膜,研究了环境温度、湿度和聚合物溶液浓度等因素对孔结构的影响.结果表明,表面活性剂是疏水性膜材质能否形成蜂窝状结构的关键因素.     

乙交酯与丙交酯共聚反应和竞聚率的测定

乳酸一羟基乙酸共聚物（PLG）是一种很好的生物医用材料，具有良好的生物相容性和生物降解性，对人体无毒害，可用作医用缝合线[1]、药物缓释胶囊[2]、内固定及牙科材料等[3]．Gilding和Reed[4]在乙交酯和丙交酯共聚反应转化率较高（12．9％～16.4％）时，利用二元共聚方?..     

改性纳米羟基磷灰石/PLGA复合材料的制备及生物活性

以低聚乳酸接枝改性的羟基磷灰石纳米粒子(op-HA)和聚丙交酯-乙交酯(PLGA)制备的生物可降解纳米复合材料(op-HA/PLGA)为研究对象, 采用FTIR, TGA, ESEM和EDX分析其接枝反应、接枝率、表面形貌和钙磷沉积情况, 通过在材料膜表面接种兔成骨细胞进行体外培养, 采用荧光染色、NIH Image J图像分析和Real-time PCR综合评价细胞在材料表面的形态、黏附面积比、增殖能力和基因表达水平, 以此评价新型骨修复纳米复合材料op-HA/PLGA的表面性质和生物活性. 研究结果表明, op-HA的表面接枝率为8.3%, 掺入至PLGA后可形成富含钙磷的粗糙表面, 促进成骨细胞的黏附、扩展和增殖, 提高Ⅰ型胶原蛋白(Collagen-Ⅰ)、骨形态蛋白-2(BMP-2)和骨连接蛋白(Osteonectin)的基因表达水平, 提高材料的钙磷沉积能力. op-HA/PLGA具有良好的细胞相容性和成骨活性.     

PCL-PEG-PCL嵌段共聚物的合成与性能

研究了氮气保护下，以辛酸亚锡和聚乙二醇为共引发剂，引发ε－己内酯的开环聚合反应。在聚乙二醇（PEG）链段分子量保持不变的情况下，全盛了不同分子量聚己丙酯链段的PCL－PEG－PCL三嵌段共聚物，以及不同分子量PEG链段而聚己内酯链段相同的嵌段共聚物。采用GPC、DSC、FTIR、^1H-NMR及吸水性测试等分析手段表征了共聚物的结构和性能。结果表明聚合反应为可控反应，可通过调整聚乙二醇与ε－己内酯的比例来控制聚合物的分子量；聚乙二醇组分的引入有效地改善了聚合物的亲水性，并破坏了其结晶性。     

乙交酯/丙交酯/己内酯三元共聚物的合成及表征

生物降解性高分子具有在生理条件下可以自行降解、最终被降解为单体或成为二氧化碳和水,从而或被机体吸收、或通过代谢途径排出体外的特性,已被广泛用作药物释放体系的载体、手术缝合线、外科手术及组织修复材料等各个方面,是当前生物医用高分子的一个重要分支．脂肪族聚酯由于具有良好生物相容性而成为最引人注意和有发展前途的一类生物降解性高分子,其中聚乙交酯（ＰＧＡ）、聚丙交酯（ＰＬＡ）及丙交酯／乙交酯共聚物（ＰＬＧＡ）是这一类聚酯中应用最为广泛的几种．Ｍｉｌｌｅｒ等［１］研究发现乙交酯（ＧＡ）和丙交酯（ＬＡ）共聚…     

三臂支化PLLA-PDLA嵌段共聚物的合成及立构复合结晶行为

以三羟甲基乙烷为起始剂, 开环聚合L-丙交酯(LLA), 合成三臂支化左旋聚乳酸(PLLA)预聚物. 采用端基活化技术对预聚物进行端羟基活化, 再与D-丙交酯(DLA)进行开环聚合, 合成了不同分子量的三臂支化左旋聚乳酸-右旋聚乳酸(PLLA-PDLA)嵌段共聚物. 采用核磁共振谱和凝胶渗透色谱等对样品的结构和分子量进行测试, 结果表明,合成的嵌段共聚物链结构具有链段立构规整度和高分子量的特点; 通过调节DLA单体与PLLA预聚物的投料比, 可实现对PLLA-PDLA嵌段共聚物的序列结构调控. 差示扫描量热仪和广角X 射线衍射结果表明, 三臂支化PLLA-PDLA嵌段共聚物的异构体分子间生成立构复合晶体, 其熔点高于200℃; 共聚物的嵌段序列结构对材料的凝聚态转变行为有很大的影响.     

二元溶剂分散法制备PLA和PLGA纳米粒

聚乳酸;聚丙交酯乙交酯;二元溶剂分散法制备PLA和PLGA纳米粒     

Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. III. Synthesis and chain‐microstructure analysis of terpolymer obtained from L‐lactide,glycolide, and ϵ‐caprolactone initiated by zirconium(IV) acetylacetonate

Zirconium(IV) acetylacetonate [Zr(acac)₄] is a very good initiator for the terpolymerization of glycolide with L‐lactide and ?‐caprolactone. The microstructure of the obtained terpolymer was determined by NMR spectroscopy and then compared with terpolymers obtained in the presence of stanous(II) octoate [Sn(oct)₂]. Samples obtained with Zr(acac)₄ were characterized by a segmental‐chain microstructure. Apart from relatively long lactidyl microblocks, there were also segments made of random copolymer of glycolide with lactide. Such a structure is formed as a result of strong transesterification caused by active caproyl chain endings attacking the glycolidyl groups. Domination of this type of transestrification is shown. The growth of terpolymer chains and the influence of transesterification on gradual changes of the microstructure of the forming terpolymer chain were examined. Significant differences among glycolide, lactide, and the least reactive caprolactone were observed. The results of differential scanning calorimetric examinations of the obtained terpolymers are presented. Differences between the structures of random terpolymers obtained during terpolymerization initiated by Sn(oct)₂ and those obtained by Zr(acac)₄ influence their thermal properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3129–3143, 2002     

AB2星型杂臂共聚物的合成及其结晶行为

通过分子设计, 用过量丁二酸酐将单硬酯酸甘油酯的两个羟基转变为羧基, 再以辛酸亚锡为催化剂, 二苯醚为共沸脱水剂, 使其进一步与不同分子量的端羟基聚乙二醇在负压下共沸脱水偶联, 成功地制备了一系列AB2星型杂臂共聚物, 并采用1H NMR、XRD、DSC、FTIR和偏光显微镜等手段对产物及其结晶行为进行了研究. 1H NMR测试结果表明, 所得聚合物是以二丁二酸甘油酯为核, 一条硬酯酸烷基(GMS)臂和两条聚乙二醇(PEG)臂构成的AB2星型杂臂共聚物[GMS-(SA-PEG)2]. DSC和XRD测试结果表明, 在GMS-(SA-PEG)2中, GMS臂和PEG臂都能结晶; GMS臂的存在不仅影响PEG臂的结晶速度, 同时也影响其结晶的完善程度, 导致结晶温度和结晶熔融温度发生变化; GMS臂相对含量越大, 对PEG结晶行为的影响也越大. 利用偏光显微镜对结晶过程的在线观察结果表明, GMS-(SA-PEG)2的结晶形貌不同于线型聚乙二醇的大球晶, 其先形成细碎的束状晶核, 然后逐步出现生长中的球晶结构, 最后所形成的晶体尺寸有大幅度的减小, 而且其形貌和PEG臂的分子量密切相关. 可见AB2星型杂臂共聚物的结晶是先由GMS臂结晶形成小晶核, 然后再诱导PEG臂球晶的生长. 杂臂的引入对于控制星型多臂共聚物的晶形、晶貌具有重要意义.     

Emulsion copolymerization of D,L‐lactide and glycolide in supercritical carbon dioxide

Biodegradable polyesters were synthesized via an emulsion polymerization in supercritical carbon dioxide (SC‐CO₂). Copolymers of lactide and glycolide were synthesized in SC‐CO₂ with stannous octoate as the ring‐opening catalyst and a fluorocarbon polymer surfactant as an emulsifying agent. The conversion of lactide and glycolide was monitored with respect to the reaction time and temperature with ¹H NMR spectroscopy. The conversion of glycolide surpassed 99% within 72 h for an SC‐CO₂ phase maintained at 200 bar and 70 °C. Under the same conditions, lactide conversion reached 65% after 72 h of polymerization. Unpolymerized monomer was removed after the reaction by extraction with an SC‐CO₂ mobile phase. The molecular weights of all the copolymers were measured by gel permeation chromatography. Weight‐average molecular weights (M_w) ranged between 2500 and 30,200 g/mol and polydispersity indices ranged from 1.4 to 2.3 for polymerization times of 6 and 48 h, respectively. Although the molecular weight increased significantly during the first 48 h of reaction, there was no significant difference in the M_w for polymerization times of 48 and 72 h. Emulsion polymerization within the benign solvent SC‐CO₂ demonstrated improved conversion and molecular weight versus polymers synthesized without surfactant. The emulsion polymerization of lactide and glycolide copolymers in SC‐CO₂ is proposed as a novel production technique for high‐purity, biodegradable polymers. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 562–570, 2001     

The effect of additives on naltrexone hydrochloride release and solvent removal rate from an injectable in situ forming PLGA implant

Biodegradable in situ forming drug delivery systems for naltrexone release are promising for post‐treatment of drug addicts. The effect of two different additives, glycerol and ethyl heptanoate, on the naltrexone hydrochloride release and solvent removal from a poly(DL ‐lactide‐co‐glycolide) (PLGA) injectable implant is presented in this article. The experimental results showed that the in vitro initial release of the drug was decreased in the presence of these additives. Ethyl heptanoate was, however, more effective than glycerol and increasing the amount of additives in PLGA solution up to 5% (w/w) resulted in a decrease of initial naltrexone release rate up to 50%. The morphological evaluation of implants using scanning electron microscopy indicated that the additives generated a less porous structure together with a finger‐like to sponge‐like transition. The solvent removal profiles of injectable implants, which can be well described by thermogravimetric and morphological analysis, were in good agreement with drug release profiles. Copyright © 2006 John Wiley & Sons, Ltd.     

Synthesis of biodegradable copolymers with low‐toxicity zirconium compounds. II. Copolymerization of glycolide with ϵ‐caprolactone initiated by zirconium(IV) acetylacetonate and zirconium(IV) chloride

The aim of this article is to show a new method of copolymerizing glycolide and caprolactone with the low‐toxicity zirconium(IV) acetylacetonate and zirconium(IV) chloride as initiators. Such initiators enabled us to obtain copolymers with very good efficiency and good mechanical properties. The reactivity of the initiators was defined, and the chain‐propagation process was examined. On the basis of an NMR examination and differential scanning calorimetry thermograms, we found that the samples obtained at 100 °C with the initiators were characterized by a segmental chain microstructure, which provided good mechanical properties. When the synthesis was carried out at 150 °C, a more randomized structure was obtained, which caused crucial changes in the properties of the copolymers and decreases in the mechanical properties. Because of their properties, the obtained copolymers could be successfully applied as degradable surgical implants or drug carriers. The results show that the copolymers obtained with zirconium(IV) acetylacetonate and chloride could successfully replace ones obtained in the presence of tin compounds as far as medical applications are concerned. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1379–1394, 2002     

聚乳酸的非等温结晶行为

用差示扫描量热法(DSC)研究聚乳酸(PLA)从熔体及玻璃态为初始条件下的非等温结晶行为,采用Ozawa方程、Mo法、Khanna法和Kissinger法对结晶动力学参数进行计算处理。 实验结果表明,这几种方法均适合处理PLA的非等温结晶过程,而Khanna法提出的结晶速率系数(CRC)能够方便地评价PLA相对结晶速率的大小。 PLA从玻璃态升温结晶比从熔体降温结晶容易得多,升温过程有利于晶核生成,而降温有利于晶体生长。 升温结晶时,升温速率2.0 ℃/min时,结晶焓(ΔH_c)达到最大为27.1 J/g。 从熔体等速降温过程中,随着冷却速率的降低ΔH_c单调增加,冷却速率为0.25 ℃/min时ΔH_c增加到28.3 J/g。 在较低温度下从玻璃态结晶,主要表现为异相成核的二维生长方式。 在较高的温度下从玻璃态升温结晶及从熔体冷却结晶时,以均相成核的三维生长方式结晶为主。 与升温过程相比,冷却不利于晶核的生成,所以导致冷却过程总体ΔH_c偏低,扩散活化能偏大。     

Simultaneous HPLC-UV Determination of Lactic Acid,Glycolic Acid,Glycolide, Lactide and Ethyl Acetate in Monomers for Producing Biodegradable Polymers

A simple, rapid high-performance liquid chromatographic (HPLC) method was developed for the simultaneous determination of glycolic acid, lactic acid, glicolide, lactide and ethyacetate in monomers for obtaining biopolymers. The separation was effected on the reversed-phase C18 column 250mm×4.6 mm with particle size 5 μ using a mobile phase mixture buffer and acetonitrile in a ratio 88:12 v/v and elution was isocratic at a flow-rate of 1.0 mL/min. The determinations were performed with a UV-Vis detector at 200 nm. The volume of the injected sample was 20 μL. Detection limits for acids and its dimers (glycolic acid, lactic acid, glicolide, lactide) and ethylacetate range between 82 and 182 ng/mL. The analytes are separated in 13 min. Recovery studies showed good results for all solutes (99–102%). The method is linear for all compounds over the concentration range tested, and shows good precision and accuracy, making it suitable for quantitation of acids and its dimers (glycolic acid, lactic acid, glicolide, lactide) and ethyl acetate in monomers.