Synthesis and characterization of multiblock copolymers based on L‐lactic acid,citric acid,and poly(ethylene glycol)

Because poly(L ‐lactic acid) (PLLA) is a biodegradable polyester with low immunogenicity and good biocompatibility, it is used as a biomaterial. However, hydrophobic PLLA does not have any reactive groups. Thus, its application is limited. To increase the hydrophilicity of PLLA and accelerate its degradation rate, functionalized pendant groups and blocks were introduced through copolymerization with citric acid and poly(ethylene glycol) (PEG), respectively. This article describes the synthesis and characterization of poly(L ‐lactic‐co‐citric acid) (PLCA)‐PLLA and PLCA‐PEG multiblock copolymers. The results indicated that the hydrolysis rate was enhanced, and the hydrophilicity was improved because of the incorporation of carboxyl groups in PLCA‐PLLA. The joining of the PEG block led to improved hydrophilicity of PLCA, and the degradation rate of PLCA‐PEG accelerated as compared with that of PLCA‐PLLA. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2073–2081, 2003     

Synthesis and characterization of amphiphilic block copolymer of polyphosphoester and poly(L‐lactic acid)

Aliphatic polyesters and polyphosphoesters (PPEs) have received much interest in medical applications due to their favorable biocompatibility and biodegradability. In this work, novel amphiphilic triblock copolymers of PPE and poly(L ‐lactic acid) (PLLA) with various compositions were synthesized and characterized. The blocky structure was confirmed by GPC analyses. These triblock copolymers formed micelles composed of hydrophobic PLLA core and hydrophilic PPE shell in aqueous solution. Critical micellization concentrations of these triblock copolymers were related to the polymer compositions. Incubation of micelles at neutral pH followed by GPC analyses revealed that these polymer micelles were hydrolysized and resulted in decreased molecular weights and small oligomers, whereas its degradation in basic and acid mediums was accelerated. MTT assay also demonstrated the biocompatibility against HEK293 cells. These biodegradable polymers are potential as drug carriers for biomedical application. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6425–6434, 2008     

Synthesis and characterization of novel degradable photocrosslinked poly(ether‐anhydride) networks

New degradable poly(ether‐anhydride) networks were synthesized by UV photopolymerization. Dicarboxylated poly(ethylene glycol) (PEG) or poly(tetramethylene glycol) (PTMG) was reacted with an excess of methacrylic anhydride to form dimethacrylated macromers containing anhydride linkages. The percent of conversion for the macromer formation was more than 80% at 60 °C after 24 h. ¹H NMR and IR spectroscopies show the presence of anhydride linkages in the macromer. In vitro degradation studies were carried out at 37 °C in PBS with crosslinked polymer networks formed by UV irradiation. All PEG‐based polymers degraded within 2 days, while PTMG‐based polymers degraded by 50% of the initial weight after 14 days. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1277–1282, 2000     

开环聚合-固相缩聚法制备立体嵌段聚乳酸

首先,采用乳酸为引发剂,辛酸亚锡为催化剂,引发丙交酯开环聚合制得具有缩聚活性的L-聚乳酸和D-聚乳酸;然后,将两者熔融共混后进行固相缩聚,合成了一系列立体嵌段聚乳酸。采用核磁共振(NMR)、凝胶渗透色谱(GPC)及差示扫描量热仪(DSC)分析了产物的链结构、重均分子量、热性能,并探讨了均相晶体和立体复合晶体共存情况下的固相缩聚机理。结果表明,固相缩聚产物分子量增长的适宜反应条件为:反应时间30h,较低的催化剂含量,L-聚乳酸质量分数为80%。L-聚乳酸和D-聚乳酸共混物较低的初始立体复合晶体结晶度有利于后续固相缩聚过程中产物分子量的增长;固相缩聚不仅发生在异链之间,而且也发生在同链之间。     

Synthesis and characterization of novel thermoresponsive‐co‐biodegradable hydrogels composed of N‐isopropylacrylamide,poly(L‐lactic acid), and dextran

A series of novel multifunctional hydrogels that combined the merits of both thermoresponsive and biodegradable polymeric materials were designed, synthesized, and characterized. The hydrogels were copolymeric networks composed of N‐isopropylacrylamide (NIPAAM) as a thermoresponsive component, poly(L‐lactic acid) (PLLA) as a hydrolytically degradable and hydrophobic component, and dextran as an enzymatically degradable and hydrophilic component. The chemical structures of the hydrogels were characterized by an attenuated total reflection–Fourier transform infrared spectroscopy (ATR–FTIR) technique. The hydrogels were thermoresponsive, showing a lower critical solution temperature (LCST) at approximately 32 °C, and their swelling properties strongly depended on temperature changes, the balance of the hydrophilic/hydrophobic components, and the degradation of the PLLA component. The degradation of the hydrogels caused by hydrolytic cleavage of ester bonds in the PLLA component was faster at 25 °C below the LCST than at 37 °C above the LCST, determined by the ATR–FTIR technique. Due to their multifunctional properties, the designed hydrogels show great potential for biomedical applications, including drug delivery and tissue engineering. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5054–5066, 2004     

Poly(lactic acid) Synthesis in Solution Polymerization

The step-growth polymerization of L-lactic acid in solution was studied in this work. In order to attain a polymer with high molecular weight, the water formed during the polymerization must be continuously removed. The use of organic solvents with high boiling point, drying agents and reduced pressure led to poly(lactic acid) (PLA) with high molecular weight, directly from the monomer. Tin (II) chloride dihydrate, SnCl₂.2H₂O, was the best of the catalysts tested as it allowed achieving PLA with a molecular weight close to 80 000 g.mol⁻¹. However, the stereoregurarity control is a severe problem in PLA synthesis by step-growth due to transesterification reactions, which lead to an inversion of the conformation and a decrease of the optical purity of the polymer. Specific rotation measurements were used in this work and showed to be a powerful technique to evaluate the racemization extent. The thermal stability of the PLA samples was evaluated by DSC which exhibits a thermal behaviour similar to the commercial Polylactide.     

Synthesis of star‐shaped poly(D,L‐lactic acid‐alt‐glycolic acid)‐b‐poly(L‐lactic acid) with the poly(D,L‐lactic acid‐alt‐glycolic acid) macroinitiator and stannous octoate catalyst

Two types of three‐arm and four‐arm, star‐shaped poly(D,L ‐lactic acid‐alt‐glycolic acid)‐b‐poly(L ‐lactic acid) (D,L ‐PLGA50‐b‐PLLA) were successfully synthesized via the sequential ring‐opening polymerization of D,L ‐3‐methylglycolide (MG) and L ‐lactide (L ‐LA) with a multifunctional initiator, such as trimethylolpropane and pentaerythritol, and stannous octoate (SnOct₂) as a catalyst. Star‐shaped, hydroxy‐terminated poly(D,L ‐lactic acid‐alt‐glycolic acid) (D,L ‐PLGA50) obtained from the polymerization of MG was used as a macroinitiator to initiate the block polymerization of L ‐LA with the SnOct₂ catalyst in bulk at 130 °C. For the polymerization of L ‐LA with the three‐arm, star‐shaped D,L ‐PLGA50 macroinitiator (number‐average molecular weight = 6800) and the SnOct₂ catalyst, the molecular weight of the resulting D,L ‐PLGA50‐b‐PLLA polymer linearly increased from 12,600 to 27,400 with the increasing molar ratio (1:1 to 3:1) of L ‐LA to MG, and the molecular weight distribution was rather narrow (weight‐average molecular weight/number‐average molecular weight = 1.09–1.15). The ¹H NMR spectrum of the D,L ‐PLGA50‐b‐PLLA block copolymer showed that the molecular weight and unit composition of the block copolymer were controlled by the molar ratio of L ‐LA to the macroinitiator. The ¹³C NMR spectrum of the block copolymer clearly showed its diblock structures, that is, D,L ‐PLGA50 as the first block and poly(L ‐lactic acid) as the second block. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 40: 409–415, 2002     

Melt polycondensation of L‐lactic acid with Sn(II) catalysts activated by various proton acids: A direct manufacturing route to high molecular weight Poly(L‐lactic acid)

Poly(L ‐lactic acid) (PLLA) was produced by the melt polycondensation of L ‐lactic acid. For the optimization of the reaction conditions, various catalyst systems were examined at different temperature and reaction times. It was discovered that Sn(II) catalysts activated by various proton acids can produce high molecular weight PLLA [weight‐average molecular weight (M_w ) ≥ 100,000] in a relatively short reaction time (≤15 h) compared with simple Sn(II)‐based catalysts (SnO, SnCl₂ · 2H₂O), which produce PLLA with an M_w of less than 30,000 after 20 h. The new catalyst system is also superior to the conventional systems in regard to racemization and discoloration of the resultant polymer. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1673–1679, 2000     

Preparation of bow tie–type methacrylated poly(caprolactone‐co‐lactic acid) scaffolds: effect of collagen modification on cell growth

A branched methacrylated poly(caprolactone‐co‐lactic acid) and methacrylated poly(tetramethylene ether glycol) (PTMG‐IEM) resins were synthesized. ¹H‐NMR spectroscopy, attenuated total reflectance Fourier transform infrared spectroscopy (ATR‐FTIR) spectroscopy, and gel permeation chromatography confirmed the chemical structures of copolymers. The photoinitiated polymerization of formulation composed of various amounts of methacrylated poly(caprolactone‐co‐lactic acid), PTMG‐IEM, poly(ethylene glycol) diacrylate, water, and photoinitiator were performed. The curing reactions were followed by photo‐DSC (Differential scanning calorimetry). Gel fraction was calculated from the insoluble part and found as ≥93%. Swelling and contact angles were measured, and all increased with the increasing amount of PTMG‐IEM in network formulations. In vitro degradation studies were performed at 37 °C in phosphate‐buffered saline (pH 7.4). Collagen‐modified polymers were also prepared and introduced as a bioactive moiety to modify the polymer to enhance cell affinity. To compare the cell adhesion affinity to the polymer with and without collagen, cell growth experiments were performed. The results showed that collagen improves the cell adhesion onto the polymer surface. With the increasing amount of collagen, cell viability increases 86% (ECV304, p < 0.05) and 83% (3 T3, p < 0.05). Copyright © 2011 John Wiley & Sons, Ltd.     

Preparation and characterization of benzoyl‐hydrazide‐derivatized poly(lactic acid) and γ‐cyclodextrin inclusion complex and its effect on the performance of poly(lactic acid)

A nucleating agent, benzyl‐hydrazide‐derivatized poly(lactic acid) (PLA) and γ‐cyclodextrin inclusion complex (PLA‐IC‐BH), was synthesized through a series of reactions. Poly(lactic acid) and γ‐cyclodextrin inclusion complex (PLA‐IC) was first obtained by ultrasonic co‐precipitation, which was then subjected to carboxylation, acylation, and amidation using benzoyl hydrazine and thionyl chloride. The composition and structure of PLA‐IC‐BH was confirmed by ¹H nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and X‐ray diffraction. PLA/PLA‐IC‐BH composites were prepared by melt blending and a hot‐press forming process. Mechanical properties, thermal stabilities, and crystallization behaviors of PLA/PLA‐IC‐BH samples were investigated by thermogravimetric analysis, differential scanning calorimetry (DSC), polarized optical microscopy (POM), rheological analysis, and so on. Mechanical testing and thermogravimetric analysis showed that the tensile strengths, impact properties, and thermal stabilities of PLA/PLA‐IC‐BH composites were improved significantly compared to pure PLA and PLA/PLA‐IC. DSC results showed that crystallinity of PLA was increased from 5.17% to 38.93% after introduction of PLA‐IC‐BH. POM results showed that PLA‐IC‐BH acted as a nucleating agent for PLA and enhanced its crystallization rate. Rotational rheological behaviors of PLA/PLA‐IC‐BH demonstrated that incorporation of PLA‐IC‐BH increased the rigidity of the network structure of the PLA matrix. Compared to those of PLA, the maximum torque and apparent viscosity of PLA/PLA‐IC‐BH composites were increased by 55.56% and 25.59%, respectively. Copyright © 2017 John Wiley & Sons, Ltd.     

Design,Synthesis and Characterization of A Novel Cationic Polymer Poly(lactic acid-b-L-lysine)

A novel biodegradable block copolymer poly(lactic acid-b-lysine) (PLA-b-PLL) has been synthesized and characterized in this study. This product was synthesized via a five-step reaction: Synthesis of hydroxyl-tailed poly(lactic acid) (PLA) by the ring-opening polymerization (ROP) of D,L-lactide in the presence of stannous octoate (Sn(OCt)₂) as initiator; coupling N-t-butoxycarbonyl-L-phenylalanine to hydroxyl-tailed PLA using dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP); the amino-tailed PLA was obtained through de-protection of the Boc-protective group in trifluoroacetic acid (TFA) solution; and then ring-opening polymerization of N ^ε -(Z)-lysine-N-carboxyanhydride (NCA) using the amino-tailed PLA as macro-initiator; finally removal of the Cbz-protective group of PLA-b-poly(N ^ε -(Z)-L-lysine) (PLA-b-PLL(Z) in a mixed hydrobromic acid/acetic acid solution to give the target copolymer. The characterization of this copolymer and its precursors were performed by ¹H-NMR, FTIR and GPC. The block copolymer PLA-b-PLL, combining the characteristics of an aliphatic polyester and poly(amino acids), could be of potential interest in a variety of medical applications, such as the fields of targeted drug delivery and gene delivery systems.     

聚乳酸/蒙脱土纳米复合材料的结构和热性能

聚乳酸/蒙脱土纳米复合材料的结构和热性能;聚乳酸;蒙脱土;纳米复合材料;插层     

Gas‐forming poly(ethylene glycol)‐b‐poly(L‐lactic acid) micelles

In this study, a novel drug‐carrying micelle composed of methoxy poly(ethylene glycol) (mPEG)‐b‐poly(L‐lactic acid) (PLLA) with gas‐forming carbonate linkage was fabricated. Here, the gas‐forming carbonate linkage was formed by the chemical coupling of the terminal hydroxyl group of the PLLA block and benzyl chloroformate (BC). mPEG‐b‐PLLA‐BC was self‐organized in aqueous solution: the PEG block on the hydrophilic outer shell and the PLLA‐BC block in the hydrophoboic innor core. The cleavage of carbonate linkage by hydrolysis and formation of carbon dioxide nanobubbles in the micellar core enabled an accelerated release of the encapsulated anticancer drug (doxorubicin: DOX) from the mPEG‐b‐PLLA‐BC micelles. The amount of drug (DOX) released from the mPEG‐b‐PLLA‐BC micelle was higher than that from the conventional mPEG‐b‐PLLA micelle, which allowed for increased in vitro toxicity against KB tumor cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Structure and wettability relationship of coelectrospun poly (L‐lactic acid)/gelatin composite fibrous mats

Coelectrospun polylactide(PLA)/gelatin (GE) composite fibrous matrixes have been identified to exhibit much improved performances compared to the respective components; however, the reasons for their water contact angles decreasing to zero at proper PLA/GE ratios remain unclear. To get a deep understanding of the phenomenon, PLA and GE were coelectrospun with different PLA/GE ratios in this study. Although the resulting composite fibers were homogeneous in appearance, they were detected different microscopic structures by transmission electron mircroscope (TEM) and via morphological observations after selective removal of either PLA or GE component. Together with the results of degradation study in phosphate buffered solution, a kind of cocontinuous phase separation microstructure could be identified for the PLA(50 wt%)/GE(50 wt%) composite fibers, which also showed the water contact angle of 0°. This value was far lower than those of electrospun PLA (～123°) and GE (～42°) fibrous matrixes. The X‐ray photoelectron spectrometry (XPS) data revealed that the polar side groups of protein macromolecules have moved toward composite fiber surface with solvent evaporation during electrospinning, due to the hydrophobic interaction between PLA and GE. Then the excellent hydrophilicity of PLA(50 wt%)/GE(50 wt%) composite fibers could be suggested as the consequence of: (1) the cocontinuous phase separation structure could provide more interface and void for water molecules penetrating; and (2) the accumulation of polar groups on composite fiber surface significantly increased the surface wettability. Copyright © 2010 John Wiley & Sons, Ltd.     

Hydrogen bonding assists stereocomplexation in poly(l‐lactic acid)/poly(d‐lactic acid) racemic blends

In this communication, we reported the sequence variation of stereocomplex crystals (SC) and homocrystals (HC) in poly(l ‐lactic acid)/poly(d ‐lactic acid) (PLLA/PDLA) racemic blends melts. It was evidenced that the emerging sequence of the SC and HC depends on the hydrogen bond formation in the melt, and the hydrogen bond is required for the stereocomplexation in PLLA/PDLA racemic blend. First, by combining a commercial fast‐scan chip‐calorimeter (Flash DSC 1) and micro‐FTIR, we found that hydrogen bonds were formed in the melt during cooling at 2.5 K/s, but not at 3000 K/s. Second, annealing the melt without hydrogen bonds at 100 °C led to HC emerging first, while annealing the melt with hydrogen bonds resulted in SC emerging at first. Third, the crystallization kinetics of the racemic blends after cooling to predefined T_c at 2.5 or 3000 K/s further verified that the hydrogen bonding can be inhibited effectively by cooling the racemic blends isotropic melt at fast enough rate. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019 , 57, 83–88     

聚丁二酸丁二醇酯与氯醚弹性体协同增韧改性聚乳酸多元共混体系

以来源于可再生资源聚丁二酸丁二醇酯(PBS)和氯醚橡胶(ECO)作为聚乳酸(PLA)的增韧改性剂,通过熔融共混的方法制备了PLA/PBS/ECO三元共混体系。动态力学分析和扫描电子显微镜结果表明,ECO促进了PBS和PLA之间的相容性。力学性能测试表明,ECO与PBS可实现对聚乳酸基体的协同增韧: PLA/PBS/ECO(70/20/10)显示出最优的拉伸性能,断裂伸长率高达270%;PLA/PBS/ECO(70/10/20)的冲击强度提高至23.7 kJ/m²,是纯聚乳酸的12倍。结合形态结构和冲击断面形貌分析表明ECO的存在可起到增容/增韧双重作用, 与柔性PBS产生良好的协同效应,有效改善聚乳酸材料的韧性。我们的研究表明,构造PLA-柔性生物聚酯和生物基弹性体多元共混体系是一种获得高性能生物基材料简单高效的手段。     

Thermally produced biodegradable scaffolds for cartilage tissue engineering

A novel process was developed to fabricate biodegradable polymer scaffolds for tissue engineering applications, without using organic solvents. Solvent residues in scaffolds fabricated by processes involving organic solvents may damage cells transplanted onto the scaffolds or tissue near the transplantation site. Poly(L-lactic acid) (PLLA) powder and NaCl particles in a mold were compressed and subsequently heated at 180 degrees C (near the PLLA melting temperature) for 3 min. The heat treatment caused the polymer particles to fuse and form a continuous matrix containing entrapped NaCl particles. After dissolving the NaCl salts, which served as a porogen, porous biodegradable PLLA scaffolds were formed. The scaffold porosity and pore size were controlled by adjusting the NaCl/PLLA weight ratio and the NaCl particle size. The characteristics of the scaffolds were compared to those of scaffolds fabricated using a conventional solvent casting/particulate leaching (SC/PL) process, in terms of pore structure, pore-size distribution, and mechanical properties. A scanning electron microscopic examination showed highly interconnected and open pore structures in the scaffolds fabricated using the thermal process, whereas the SC/PL process yielded scaffolds with less interconnected and closed pore structures. Mercury intrusion porosimetry revealed that the thermally produced scaffolds had a much more uniform distribution of pore sizes than the SC/PL process. The utility of the thermally produced scaffolds was demonstrated by engineering cartilaginous tissues in vivo. In summary, the thermal process developed in this study yields tissue-engineering scaffolds with more favorable characteristics, with respect to, freedom from organic solvents, pore structure, and size distribution than the SC/PL process. Moreover, the thermal process could also be used to fabricate scaffolds from polymers that are insoluble in organic solvents, such as poly(glycolic acid). Cartilage tissue regenerated from thermally produced PLLA scaffold.     

Enhanced properties of poly(lactic acid) with silica nanoparticles

The objective of this article is to fabricate poly(lactic acid) (PLA) and nano silica (SiO₂) composites and investigate effect of SiO₂ on the properties of PLA composites. Surface‐grafting modification was used in this study by grafting 3‐Glycidoxypropyltrimethoxysilane (KH‐560) onto the surface of silica nanoparticles. The surface‐grafting reaction was confirmed by Fourier transform infrared spectroscopy and thermogravimetric analysis. Then the hydrophilic silica nanoparticles became hydrophobic and dispersed homogeneously in PLA matrix. Scanning electron microscope and Dynamic thermomechanical analysis (DMA) results revealed that the compatibility between PLA and SiO₂ was improved. Differential scanning calorimetry and polarized optical microscope tests showed that nano‐silica had a good effect on crystallization of PLA. The transparency analysis showed an increase in transparency of PLA, which had great benefit for the application of PLA. The thermal stability, fire resistance, and mechanical properties were also enhanced because of the addition of nano silica particles. Copyright © 2016 John Wiley & Sons, Ltd.     

Stereoblock poly(lactic acid): synthesis via solid-state polycondensation of a stereocomplexed mixture of poly(L-lactic acid) and poly(D-lactic acid)

Stereoblock poly(lactic acid) consisting of D- and L-lactate stereosequences can be successfully synthesized by solid-state polycondensation of a 1:1 mixture of poly(L-lactic acid) and poly(D-lactic acid). In the first step, melt-polycondensation of L- and D-lactic acids is conducted to synthesize poly(L-lactic acid) and poly(D-lactic acid) with a medium-molecular-weight, respectively. In the next step, these poly(L-lactic acid) and poly(D-lactic acid) are melt-blended in 1:1 ratio to allow formation of their stereocomplex. In the last step, this melt-blend is subjected to solid-state polycondensation at temperature where the dehydrative condensation is allowed to promote chain extension in the amorphous phase with the stereocomplex crystals preserved. Finally, stereoblock poly(lactic acid) having high-molecular-weight is obtained. The stereoblock poly(lactic acid) synthesized by this way shows a higher melting temperature in consequence of the controlled block lengths and the resulting higher-molecular-weight. The product characterization as well as the optimization of the polymerization conditions is described. Changes in M(w) of stereoblock poly(lactic acid) (sb-PLA) as a function of the reaction time.