Copolyesters from Soybean Oil for Use as Resorbable Biomaterials

A family of soybean oil (SO) based biodegradable cross-linked copolyesters sourced from renewable resources was developed for use as resorbable biomaterials. The polyesters were prepared by a melt condensation of epoxidized soybean oil polyol and sebacic acid with citric acid (CA) as a cross-linker. D-Mannitol (M) was added as an additional reactant to improve mechanical properties. Differential scanning calorimetry revealed that the polyester synthesized using only CA as the cross-linker was semicrystalline and elastomeric at physiological temperature. The polymers were hydrophobic in nature. The water wettability, elongation at break and the degradation rate of the polyesters decreased with increase in M content or curing time. Modeling of release kinetics of dyes showed a diffusion controlled mechanism underlies the observed sustained release from these polymers. The polyesters supported attachment and proliferation of human stem cells and were thus cytocompatible. Porous scaffolds induced osteogenic differentiation of the stern cells suggesting that these polymers are well suited for bone tissue engineering. Thus, this family of polyesters offers a low cost and green alternative as biocompatible, bioresobable polymers for potential use as resorbable biomaterials for tissue engineering and controlled release.

Periodically Grafted Amphiphilic Copolymers: Effects of Steric Crowding and Reversal of Amphiphilicity

Two series of periodically clickable polyesters were prepared; one of them carries alkylene segments along its backbone, whereas the other carries poly(ethylene glycol) (PEG) segments. These polyesters were clicked with either MPEG-350 azide or docosyl (C22) azide to yield periodically grafted amphiphilic copolymers (PGACs) carrying either flexible hydrophilic or crystallizable hydrophobic backbone segments. The immiscibility between hydrocarbon and PEG segments causes both of these systems to fold in either a zigzag or hairpin-like conformation; the hairpin-like conformation appears to be preferred when flexible PEG segments are present in the backbone. The folded chains further reorganize in the solid state to develop a lamellar morphology that permits the collocation of the PEG and hydrocarbon (HC) segments within alternate domains; evidence for the self-segregation was gained from DSC, SAXS, and AFM studies. SAXS studies revealed the formation of an extended lamellar structure, whereas AFM images showed uniform layered morphology with layer heights that matched reasonably well with the interlamellar spacing obtained from the SAXS study. Labeling One representative PGAC, carrying crystallizable long alkylene segments in the backbone and pendant PEG-350 side chains, with a small mole fraction of pyrene fluorophore permitted the examination of the conformational transition that occurs upon going from a good to a poor solvent; this single-chain folded conformation, we postulate, is the intermediate that organizes into the lamellar morphology.

Molecular Dynamics Study of the Structure, Flexibility, and Hydrophilicity of PETIM Dendrimers: A Comparison with PAMAM Dendrimers

A new class of dendrimers, the poly(propyl ether imine) (PETIM) dendrimer, has been shown to be a novel hyperbranched polymer having potential applications as a drug delivery vehicle. Structure and dynamics of the amine terminated PETIM dendrimer and their changes with respect to the dendrimer generation are poorly understood. Since most drugs are hydrophobic in nature, the extent of hydrophobicity of the dendrimer core is related to its drug encapsulation and retention efficacy. In this study, we carry out fully atomistic molecular dynamics (MD) simulations to characterize the structure of PETIM (G2-G6) dendrimers in salt solution as a function of dendrimer generation at different protonation levels. Structural properties such as radius of gyration (R-g), radial density distribution, aspect ratio, and asphericity are calculated. In order to assess the hydrophilicity of the dendrimer, we compute the number of bound water molecules in the interior of dendrirner as well as the number of dendrimer-water hydrogen bonds. We conclude that PETIM dendrimers have relatively greater hydrophobicity and flexibility when compared with their extensively investigated PAMAM counterparts. Hence PETIM dendrimers are expected to have stronger interactions with lipid membranes as well as improved drug encapsulation and retention properties when compared with PAMAM dendrimers. We compute the root-mean-square fluctuation of dendrimers as well as their entropy to quantify the flexibility of the dendrimer. Finally we note that structural and solvation properties computed using force field parameters derived based on the CHARMM general purpose force field were in good quantitative agreement with those obtained using the generalized Amber force field (GAFF).

钙催化剂在生物降解脂肪族聚酯合成中的应用

生物降解高分子在环境保护以及组织工程、药物控制释放、骨固定等医药领域有着广泛的应用。特别是以聚丙交酷（PLA）、聚乙交酯（PGA）、聚。一己内酯（PCL）以及它们的共聚物为代表的化学合成生物降解高分子材料，由于具有优异的性能、可以大规模生产、成本较低等优点，得到了人们广泛的关注。作为生物医用材料，对无毒性的要求很严。而现在所用的脂肪族聚酯大都是用金属盐、金属有机化合物等作为催化剂合成出来的，不可避免残留一些催化剂所用的金属元素。研究表明，即使是已经获得美国FDA批准的，现在用得最普遍的辛酸亚锡所残留的锡也可能引起一些细胞毒性。因此对毒性小且活性高的催化剂的研究是非常有意义。钙离子对人体是没有毒性的，因而这几年已引起了人们的兴趣，但文献中报道的钙催化剂，如CaHZ等，催化活性尚不够让人满意。本文对高效的钙催化剂在生物降解脂肪族聚酯中的应用进行详细的研究，得到了一些有意义的结论：1、用EO和PO处理的有机氨钙催化剂（Ca／EO和Ca／PO）聚合了CL和LLA。发现CL聚合速度很快，M／I=650时70℃反应3h后收率已达到90％以上，LLA的聚合速度比CL要慢，M／I=650、70℃反应10h后收率才达到90％以上。以上聚合反应有明显的活性聚合的特点：反应初期Mv和收率和聚合时间呈线性关系；Mv在一定范围内和M／I成线性关系。2、用红外、原子吸收和核磁共振等分析手段阐明了有机氨钙催化剂的结构：结构，而且这两个催化剂的活性中心分别是均是Ca-O键。CL和LLA的开环聚合可能是以配位一插入的机理进行的。3、用C。／PO催化剂聚合LLA时有一定程度的消旋化反应发生，曳NMR研究表明相当于88％的LLA和12％外消旋以共聚。提高反应温度到110℃时比旋光度只有-125℃说明消旋化反应比较严重。4、用C。／PO催化剂先聚合CL再聚合LLA的方法合成了PCL-PLA两嵌段共聚物，并用泊NMR，13C NMR，GPC，DSC，WAXD进行了表征。其绝对和相对分子量可以通过M／I和投料比进行控制。定量碳谱图表明有较严重的消旋化反应发生，相当于84％的LLA和16％外消旋LA共聚。DSC和似XD分析表明，PLA段的分子量小时PLA段不结晶，当PLA段的分子量达到一定程度（3000以上）后PCL一PLA嵌段共聚物有相分离现象发生。5、以各种分子量的PEG为引发剂用氨钙催化剂和开环聚合CL，合成了一系列PCL-PEG-PCL三嵌段共聚物，并用妞NMR，laCNMR，GPC，DSC，做XD进行了表征。聚合物的结构可以通过改变PEG的分子量和CL／PEG投料比来调整。从DSC和wAXD分析可以得出以下几个结论：PCL-PEG-PCL嵌段共聚物有相分离现象发生，形成PCL和PEG微相区域；PEG段的结晶行为受先结晶的PCL段的影响；PCL段的分子量越大PEG段的Tc和Tm越低，其结晶度越低。6、以各种分子量的PEG为引发剂用氨钙催化剂80℃下开环聚合LLA24小时，合成了一系列PLA-PEG-PLA三嵌段共聚物，和别的催化剂比起来温度低得多，反应时间也短得多。可以通过改变PEG的分子量和CL／PEG投料比来调整聚合物的结构。DSC和WAXD分析表明，PLA-PEG-PLA三嵌段共聚物中PEG段的结晶能力受PLA段的影响非常大：当PEG段的分子量很小时（如1000）很难结晶；即使当PEG段的分子量较大时如果PLA段的分子量达到一定程度时PEG段同样也不结晶；而且PLA段的结晶行为受本身分子量的影响比较大，其Tc和伽随着分子量增加有较大的提高。7、合成了MPEG-PLA两嵌段共聚物，发现合成PLA段的分子量大的聚合物比较困难，MPEG-PCL两嵌段共聚物很难合成。DsC和WAXD分析表明，PLA段对MPEG段结晶有一定程度的影响，但是比三嵌段共聚物的影响要小得多。8、用荧光光谱和IHNMR研究了上面合成出的几个样品的胶束行为。发现cmc由大到小的顺序为MPEG（5000）-PLA（5100），PLA（3050）-PEG（4600）-PLA（3050），PCL（2270）-PEG（5000）-PCL（2270），PCL（4600）-PEG（4600）-PCL（4600）。PCL-PEG-PCL三嵌段共聚物在水中形成了具有核一壳结构的胶束。9、以苯甲醇处理的有机氨钙催化剂开环聚合了CL。泊NMR谱图表明得到的聚合物具有苯端基。这一结果为用硝苯基乙醇代替苯甲醇制备催化剂，然后开环聚合CL或LA得到硝基苯端基的脂肪族聚酯打下了实验基础。

可生物降解脂肪族聚酯的反应接枝与相形态

聚（β-轻基丁酸醋-co-β-经基戊酸酷）（PHBV）是一种生物降解脂肪族聚酷，其结晶成核密度低，结晶速度比较慢且易生成大尺寸的球晶。以球晶中心向外扩展形成许多圆环状的开裂以及沿球晶生长方向形成许多劈裂，从而导致了PHBV呈脆性断裂。只要能有效地降低其结晶度，减小球晶尺寸，就可以达到增韧的目的。通过PHBV与二氧化碳一环氧丙烷共聚物（PPC）反应接枝来调控PHBV的结构和相形态，具有实际的理论意义和应用前景。开展了PPC的封端和与PHBv的接枝反应。首次提出了甲基丙烯酸缩水甘油醋（GMA）与PHBV及PPC与PHBV－GMA的接枝反应机理。确信PHBV接枝GMA的接枝点发生在PHBV骨架上的季碳原子上，反应过程中没有交联反应和降解反应的发生。发现PHBv-g-Gh1A共聚物上环氧基能与封端的PPc上的梭基熔融反应原位生成了PHBv-g-PPC共聚物。在机械共混物中两大分子之间的接枝和醋交换反应几乎不发生。GMA的引入阻止了PHBV的降解行为，从而改善了PHBV的加工性能。成功地调控了PHBVPC结构及相形态。证实了PHBV与PPC在反应共混过程中的接枝反应。加入PPC阻碍了PHBV的结晶，这在反应体系中更加明显。通过控制反应条件和反应物的组成，可以使非反应共混物中PHBV球晶变得不规则，发生扭曲变形，球晶尺寸降低；而在反应共混物中，可以使其球晶已很难辨认。SEM结果表明在PHBV用PC（30／70）和PHBV用PC（70／30）共混物中发生了相转变。尤其在反应共混物中淬断面表现为塑性。力学性能随共混组成而发生较大幅度的改变。发现通过改变组成及对反应共混相结构的控制，PHBV共混物的断裂伸长率可变化1一2个数量级，从而实现了制得一系列从脆性断裂塑料到高韧性弹性体的高分子材料。研究了反应接枝共混体系的熔融、结晶行为、等温和非等温结晶动力学。发现加入的GMA对PHBV有成核作用。引入的PPC阻碍了PHBV的结晶，降低PHBV的结晶度，球晶径向生长速率，平衡熔点和结晶能力。结晶速率与冷却速率有较大的依赖性。修正的Avrami方程能很好地描述PHBv和PHBv爪PC共混物非等温结晶过程。对动态力学性能的分析发现，反应共混物相比于非反应共混物聚合物玻璃化温度都有不同程度的内移，说明两组分间相容性增加，接枝共聚物具有良好的增容效果，显著地改善了两相界面性能。PHBV可以部分进入PPC相区，使共混物分子运动特征发生改变。发现在熔体加工条件下，PHBV与PPC之间很难发生酷交换反应，但是以辛酸亚锡为催化剂，氯苯为溶剂，在120℃条件下，两者可以发生醋交换反应。在聚己内醋（PCL）用PC熔融共混过程中GMA可以有效地抑制过氧化二异丙苯（DCP）所引起的PCL交联反应。在DCP和OMA存在下得到的样品之球晶具有十字消光现象，球晶规整度增大。同在溶液中醋交换催化剂存在下PPC和PCL发生了酷交换反应后所形成的球晶相结构相类似，而PCL／PPCOCP体系所形成的球晶中含有大量的非晶相区。从而，确信了GMA在脂肪族聚醋，脂肪族聚碳酸醋等生物降解高分子反应共混体系中的双重作用：一是引入具有高反应活性的官能团；二是减少在过氧化物作用下PHBV类高分子的降解及PCL类高分子的交联反应。PCL共混组分可以提高PPC相区的稳定性。提高反应时间或催化剂浓度同样能够改善热稳定性。

新型超支化聚合物的合成和表征

超支化聚合物是一类高度支化的具有三维椭球状立体构造的大分子。由于具有传统线形聚合物所没有的低粘度、高流变、良好的溶解性及大量末端官能团等物理化学特性，近年来已成为高分子科学界研究的一个热点。十多年来，人们在合成方法、表征手段、应用及理论研究等方面取得了可喜的成就。但是，目前超支化聚合物的发展还存在着合成方法和所合成的聚合物种类有限，成本较高及结构可控性差等问题。设计合成了五个系列的新型ABx单体，二经基苯氯代苯酞亚胺、二乙酞氧基苯甲酸苯酞亚胺、三乙酞氧基苯酞胺酸，二经基苯基联苯酰胺酸和多轻基烷基联苯酞胺酸，再分别通过缩聚反应一步成功制备了新型芳香超支化聚醚酞亚胺、芳香超支化聚酷酰亚胺，可降解的超支化聚酷酞胺、芳香和半芳香超支化聚酯酞胺。通过傅立叶红外光谱（FT）、核磁共振波谱（NMR）凝胶渗透色谱（GPC）、热差（DSC）和热重（TGA）等分析手段，详细研究了它们的结构和性质，这些聚合物都具有较低的粘度、良好的溶解性和热稳定性。末端基团的种类和性质在很大程度上影响聚合物的性质。通过小角X一射线散射仪和紫外一可见光谱研究了由天然原料制备的超支化聚酷酞胺的降解行为。设计了由商品化原料，二梭酸酐（AAA，型）与二乙醇胺归32型）、脂肪二梭酸配与多经基伯胺（CBx型）和二酸（Az型）与多轻基伯胺一步合成超支化聚合物的新方法，成功地合成了二十四种不同结构的新型超支化聚酷酰胺。通过FTIR、NMR和DEPT NMR、GPC、基质辅助激光解析时间飞行质谱（MALDI-TOF-MS）、DSC和TGA等分析手段，详细研究了它们的结构和性质。这些聚合物都具有较低的粘度、良好的溶解性。

Microspheres and microcapsules, a survey of manufacturing techniques: Part III: Solvent evaporation

A methodological survey of microsphere formation and microencapsulation techniques based on solvent extraction/evaporation techniques is presented. Thus, basic features of solvent extraction and solvent evaporation processes, including droplet formation, droplet/particle stabilization, and solvent removal, are outlined. Preparation of a wide range of microspherical and microcapsular products based on biodegradable polyesters, polysaccharides, and nonbiodegradable polymers are discussed. Dependence of microcapsule characteristics on manufacturing parameters, as well as performance evaluation of microspherical and microcapsular products, are also briefly covered.

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 and characterization of novel biodegradable poly(carbonate ester)s with photolabile protecting groups

Novel biodegradable poly(carbonate ester)s with photolabile protecting groups were synthesized by ring-opening copolymerization Of L-lactide (LA) with 5-methyl-5-(2-nitro-benzoxycarbonyl)-1,3-dioxan-2-one (MNC) with diethyl zinc (Et2Zn) as catalyst. The poly(L-lactide-co-5-methyl-5-carboxyl-1,3-dioxan-2-one) (P(LA-co-MCC)) was obtained by UV irradiation Of poly(L-lactide acid-co-5-methyl-5-(2-nitro-benzoxycarbonyl)-1,3-dioxan-2-one) (P(LA-co-MNC)) to remove the protective 2-nitrobenzyl group.

The immobilization of proteins on biodegradable polymer fibers via click chemistry

A facile and efficient method to immobilize bioactive proteins onto polymeric substrate was established. Testis-specific protease 50 (TSP50) was immobilized on ultrafine biodegradable polymer fibers, i.e., (1) to prepare a propargyl-containing polymer P(LA90-co-MPCIO) by introducing propargyl group into a cyclic carbonate monomer (5-methyl-5-propargyloxycarbonyl-1,3-dioxan2-one, MPC) and copolymerizing it with L-lactide; (2) to electrospin the functionalized polymer into ultrafine fibers; (3) to azidize the TSP50, and (4) to perform the click reaction between the propargyl groups on the fibers and the azido groups on the protein.

Novel aliphatic poly(ester-carhonate) with pendant allyl ester groups and its folic acid functionalization

A series of novel poly(ester-carbonate)s bearing pendant allyl ester groups P(LA-co-MAC)s were prepared by ring-opening copolymerization Of L-lactide (LA) and 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) with diethyl zinc (ZnEt2) as initiator. NMR analysis investigated the microstructure of the copolymer. DSC results indicated that the copolymers displayed a single glass-transition temperature (T-g), which was indicative of a random copolymer, and the Tg decreased with increasing carbonate content in the copolymer.

Branched polystyrene with abundant pendant vinyl functional groups from asymmetric divinyl monomer

Branched polystyrenes with abundant pendant vinyl functional groups were prepared via radical polymerization of an asymmetric divinyl monomer, which possesses a higher reactive styryl and a lower reactive butenyl. Employing a fast reversible addition fragmentation chain transfer (RAFT) equilibrium, the concentration of active propagation chains remained at a low value and thus crosslinking did not occur until a high level of monomer conversion. The combination of a higher reaction temperature (120 degrees C) and RAFT agent cumyl dithiobenzoate was demonstrated to be optimal for providing both a more highly branched architecture and a higher polymer yield.

A quantitative HPLC method for determining lactide content using hydrolytic kinetics

A new method for quantitative analysis of lactide has been developed by applying chemical kinetics to a HPLC system. The most important advance is its practical approach to the quantification of analytes that are unstable in the HPLC mobile phase. In HPLC analysis, anhydrous mobile phases cannot separate lactide from impurities, and only mixtures of water and organic solvent can achieve effective separation. By selecting conditions for testing and studying the kinetics of lactide hydrolysis, extensive experiments revealed that lactide degradation can be treated as a pseudo-first-order reaction under the given HPLC conditions, and lactide content or purity can be quantitatively determined. This method is practical for measuring the purity of the intermediate lactide in polylactic acid (PLA) production and the lactide content in PLA.

Thermomechanical and Optical Properties of Biodegradable Poly(L-lactide)/Silica Nanocomposites by Melt Compounding

Poly(L-lactide) (PLA)/silica (SiO2) nanocomposites containing 1, 3, 5, 7, and 10 Wt % SiO2 nanoparticles were prepared by melt compounding in a Haake mixer. The phase morphology, thermomechanical properties, and optical transparency were investigated and compared to those of neat PLA. Scanning electron microscopy results show that the SiO2 nanoparticles were uniformly distributed in the PLA matrix for filler contents below 5 wt %, whereas some aggregates were detected with further increasing filler concentration. Differential scanning calorimetry analysis revealed that the addition Of SiO2 nanoparticles not only remarkably accelerated the crystallization speed but also largely improved the crystallinity of PLA. An initial increase followed by a decrease with higher filler loadings for the storage modulus and glass-transition temperature were observed according to dynamic mechanical analysis results. Hydrogen bonding interaction involving C=O of PLA with Si-OH Of SiO2 was evidenced by Fourier transform infrared analysis for the first time.