XPS and wettability characterization of modified poly(lactic acid) and poly(lactic/glycolic acid) films

Poly(lactic acid) (PLA) and poly(lactic/glycolic acid) copolymers (PLGA) are biodegradable drug carriers of great importance, although successful pharmaceutical application requires adjustment of the surface properties of the polymeric drug delivery system to be compatible with the biological environment. For that reason, reduction of the original hydrophobicity of the PLA or PLGA surfaces was performed by applying a hydrophilic polymer poly(ethylene oxide) (PEO) with the aim to improve biocompatibility of the original polymer. PEO-containing surfaces were prepared by incorporation of block copolymeric surfactants, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic), into the hydrophobic surface. Films of polymer blends from PLA or PLGA (with lactic/glycolic acid ratios of 75/25 and 50/50) and from Pluronics (PE6800, PE6400, and PE6100) were obtained by the solvent casting method, applying the Pluronics at different concentrations between 1 and 9.1% w/w. Wettability was measured to monitor the change in surface hydrophobicity, while X-ray photoelectron spectroscopy (XPS) was applied to determine the composition and chemical structure of the polymer surface and its change with surface modification. Substantial reduction of surface hydrophobicity was achieved on both the PLA homopolymer and the PLGA copolymers by applying the Pluronics at various concentrations. In accordance with the wettability changes the accumulation of Pluronics in the surface layer was greatly affected by the initial hydrophobicity of the polymer, namely, by the lactide content of the copolymer. The extent of surface modification was also found to be dependent on the type of blended Pluronics. Surface activity of the modifying Pluronic component was interpreted by using the solubility parameters.     

Wettability of biodegradable surfaces

The study of the interfacial characteristics of biodegradable polymers/copolymers is of importance from the point of view of both surface science and pharmaceutical/cosmetic applications. Films formed from biodegradable polymers allow systematic wettability studies on surfaces with a wide range of copolymer (chemical) compositions. The possibility of interchanging these drug carrier polymers, if their wetting characteristics are similar, could be beneficial to diverse applications. Low-rate dynamic contact angles on films (solvent cast on polar substrates, i.e. on silicon wafer) of poly(lactic acid), and its copolymers with poly(glycolic acid), (with four different copolymer ratios of 85/15, 75/25, 65/35 and 50/50) were measured by axisymmetric drop shape analysis-profile (ADSA-P) with four liquids: water, formamide, 2,2′-thiodiethanol and 3-pyridylcarbinol. The solid surface tensions, γ_sv, were calculated from the advancing contact angles, θ_A. The surface topography of the polymer films was investigated by atomic force microscopy (AFM). The surface composition of the polymer layers was analyzed by X-ray photoelectron spectroscopy (XPS). The advancing contact angles were found to be independent of the composition of the copolymers, while the receding angles, θ_R, did decrease with increasing ratio of the polar component [poly(glycolic acid)] in the copolymers. The solid surface tensions calculated from the advancing contact angles of the liquids for all homo- and copolymers were the same within the error limit; the mean value being γ_sv=35.6 ± 0.2 mJ/m². The surface roughness, which was obtained from AFM images, increased with increasing poly(glycolic acid) ratio, without affecting the advancing contact angles. The constancy of γ_sv is attributed to the effect of the surface activity of the nonpolar segments of the polymer chains, which oriented to form the outermost layer of the film. This was confirmed by XPS analysis. Received: 06 November 2000 Accepted: 09 May 2001     

Degradation kinetics of poly(lactic-co-glycolic) acid block copolymer cast films in phosphate buffer solution as revealed by infrared and Raman spectroscopies

Poly(lactic-co-glycolic) acid (PLGA) is an important copolymer used in drug delivery platforms where controlled release is required. In this work we investigated the in vitro degradation of four PLGA copolymers with L/G molar compositions of 50/50, 65/35, 75/25 and 95/5. ATR-IR and Raman spectroscopies were used to differentiate and quantify the degradation rates of glycolic and lactic units. Both techniques were used to determine the polymer composition as a function of degradation time and the degradation rate constants for the hydrolysis of glycolic and lactic units were calculated using a 1st order kinetics approach. Our results revealed a two stage process for the degradation of PLGA cast films in PBS in agreement with our previous work. The degradation rate constant for glycolic unit was found to be 1.3 times higher than for lactic units. In addition the degradation rate constants for L and G units were shown to decrease proportionally with increasing initial lactic content of the copolymer used to prepare the films.     

引入δ-内酯疏水取代烷基结构实现聚对二氧环己酮的性能调控

可反复化学循环、可生物降解的聚对二氧环己酮(PPDO),存在水解降解快等问题,不利于其储存和使用.基于此,本文通过将不同正烷基取代的δ-内酯(RVL)分别与对二氧环己酮(PDO)在磷酸二苯酯催化下本体共聚,高效地合成了3种结构和组分可控的PPDO基共聚物(PDRVL).通过热重分析(TGA)、差示扫描量热分析(DSC)...     

含悬挂羧基手臂聚乳酸材料的合成与血小板粘附性研究

制备了乳酸-β-苹果酸共聚物,并在此基础上进一步修饰合成了含悬挂羟基(PLMAHE)以及悬挂羧基(PCA-PLA)的聚乳酸共聚物,利用原子力显微镜及环境扫描电镜,观察了聚合物膜的表面形貌以及粘附在聚合物膜上的血小板数量与形态.结果表明含悬挂羟基材料表面粘附血小板时发生聚集并有伪足生成,含悬挂羧基材料表面血小板粘附数量较少且形态正常,有望成为优良的抗凝血材料.     

聚乳酸-b-聚(N~ε-苄氧羰基-L-赖氨酸)-b-聚乙二醇的合成与表征

用端氨基聚乳酸做引发剂,在DMF中引发Nε-苄氧羰基-L-赖氨酸酐(Lys(Z)-NCA)聚合,合成了端氨基聚(Nε-苄氧羰基-L-赖氨酸)-b-聚乳酸两嵌段共聚物.以端羧基聚乙二醇经NHS活化与端氨基聚(Nε-苄氧羰基-L-赖氨酸)-b-聚乳酸偶联,合成了聚(乳酸-b-Nε-苄氧羰基-L-赖氨酸-b-乙二醇)三嵌段聚合物.利用IR、1H-NMR、GPC和TEM对它们的结构、形态进行了表征,结果表明,所合成的分子量可控、分子量分布窄(Mw/Mn=1.07)的嵌段共聚物,酰化反应产率达70%以上.同时聚乙二醇和Nε-苄氧羰基-L-赖氨酸被引入到聚乳酸主链中,在聚合物侧链脱保护后有望改善聚乳酸的细胞亲和性。     

Effects of polymerization conditions on the in vitro hydrolytic degradation of plaques of poly(dl-lactic acid-block-ethylene glycol) diblock copolymers

In the case of poly(lactic acid) stereocopolymers, it has been shown that the hydrolytic degradation of derived devices depends very much on whether zinc lactate or tin octoate was used to polymerize lactides. In contrast, no effect was found in the case of nanoparticles derived from poly(dl-lactic acid)-block-poly(ethylene glycol) copolymers obtained by anionic polymerization of dl-lactide initiated by the sodium salt of monomethoxypoly(ethylene glycol) or by coordination-insertion polymerization of dl-lactide initiated by monomethoxypoly(ethylene glycol) in the presence of tin octoate as catalyst. To understand the difference of behaviour, in vitro hydrolytic degradation of thick plates made of the same copolymers but under different conditions was investigated. Changes were monitored by ¹H Nuclear Magnetic Resonance, Size Exclusion Chromatography, Electrospray Mass Spectrometry and Capillary Zone Electrophoresis. It is shown that chain cleavage occurred from the very beginning of degradation and that plates disintegrated after 13 weeks. In all cases, degradation proceeded faster inside than at the surface, in contrast to what was observed for nanoparticles. Tin-type copolymer plates degraded more slowly than sodium macroalcoholate-type ones and were sensitive to purification conditions, in contrast to the latter.     

聚乙二醇-聚乳酸共聚物药物载体

本文综述了聚乙二醇与聚乳酸共聚亲水改性的最新进展, 包括嵌段和星型结构聚乙二醇-聚乳酸共聚物(PEG-PLA)及其端基化衍生物的合成。同时概述了该共聚物以胶束、微粒、水凝胶和囊泡形式担载亲水、疏水及蛋白质类药物的应用,特别介绍了静电纺丝制备的PEG-PLA超细纤维载体及其释药特性。     

The impact of chemical composition on the degradation kinetics of poly(lactic-co-glycolic) acid copolymers cast films in phosphate buffer solution

We have investigated the in vitro degradation of poly(lactic-co-glycolic) acid copolymer with different lactic to glycolic ratio: 50:50, 65:35, 75:25, 95:05 and 100:00 (mol. %). The degradation studies were performed on solvent cast films of controlled thickness and shape. The samples were incubated at 37 °C in phosphate buffered saline solution. The degradation was followed using potentiometry, light microscopy, gravimetry, size exclusion chromatography and differential scanning calorimetry. The same degradation process, as discussed in detail in our previous article for PLGA 50:50 (E. Vey et al., J. of Polym. Deg. and Stab. 2008, 93, 1896-1876), was observed for all the samples investigated, however the time scale over which the different events/degradation steps were observed increased with increasing lactic content of the polymer. The glass transition temperatures of the films increase with lactic content and are thought to have a significant impact on the rate of diffusion of water into the films - the higher the glass transition the slower the diffusion of water - and therefore on the degradation dynamics of the films. Kinetic parameters were extracted from the acid release, molecular weight and mass loss data. In each case linear correlations between the rate constants extracted and the lactic content of the polymer were found. The overall degradation rate of the films was found to decrease with increasing lactic content.     

Elastic/adhesive double-layered PLA-PEG multiblock copolymer membranes for postoperative adhesion prevention

Tissue adhesions cause severe and life-threatening conditions, including pain, infertility, and heart defects. The purpose of this study is to develop an anti-adhesion membrane that sticks onto the injured tissues or organs in order to avoid the suturing of the membrane which may lead to the unnecessary tissue adhesion. We previously developed poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) multiblock copolymers as soft, water absorbable, and quickly degradable biomaterials. The copolymer with the highest PEG content adsorbs body fluid in vivo and sticks to the tissues. In the present study thin film and nanofiber mat were prepared from the copolymer and evaluated in vitro and in vivo. The hydrophilicity and the degradation rate increased with the increased PEG content of the multiblock copolymers. The copolymer with PEG content of 88% (LE(m)-88) was quickly swollen, become viscous, and rapidly collapsed in PBS, which was suitable feature for adhesion prevention material without suturing. Various double layered membranes with different characteristics were evaluated in vivo by applying onto the cecum scrubbed with abrasive paper, and onto the heart surface after pericardium removal. LE(m)-88 was swollen with tissue fluid and had a hydrogel-like nature. LE(m)-88 film/LE(m)-32 film double layered membrane was found to be the most effective in preventing tissue adhesion in cecum model. This excellent performance was confirmed in the rat heart adhesion model. In both models, the LE(m)-32 support film was detached from the site of application, which leads to the healing without adhesion.     

Stereocomplexes of Triblock Poly(lactide- PEG2000-lactide) as Carrier of Drugs

Triblock copolymers of poly(lactide)-poly(ethylene-glycol)-poly(lactide) (PLA-PEG₂₀₀₀-PLA) were synthesized by ring-opening polymerization of lactide and PEG₂₀₀₀ diol as co-catalyst. Stereocomplexes with particle sizes ranging from nanometers to microns were obtained by mixing acetonitrile solutions of pairs of enantiomeric homopoly(lactide) and the triblock copolymers. The stereocomplexes exhibited higher crystalline melting temperatures than the optically pure polymers. The ratio of PLA terminals in the copolymers had a significant effect on their stereocomplex degradation and drug release. These stereocomplexes were used for the encapsulation of dexamethasone for controlled release applications. Dexamethasone phosphate loading capacity, in vitro release, degradation and stability of polymers and formulation were investigated for one month. An increase in the dexamethsone phosphate content in the stereocomplex or a decrease in the PLA ratio in the copolymer resulted in a faster release of drug and polymer degradation.     

Photo-grafting Poly(acrylic acid) onto Poly(lactic acid) Chains in Solution

Poly(lactic acid)(PLA)is one of the most important bio-plastics,and chemical modification of the already-polymerized poly(lactic acid)chains may enable optimization of its material properties and expand its application areas.In this study,we demonstrated that poly(lactic acid)can be readily dissolved in acrylic acid at room temperature,and acrylic acid can be graft-polymerized onto poly(lactic acid)chains in solution with the help of photoinitiator benzophenone under 254 nm ultraviolet(UV)irradiation.Similar photo-grafting polymerization of acrylic acid(PAA)has only been studied before in the surface modification of polymer films.The graft ratio could be controlled by various reaction parameters,including irradiation time,benzophenone content,and monomer/polymer ratios.This photo-grafting reaction resulted in high graft ratio(graft ratio PAA/PLA up to 180%)without formation of homopolymers of acrylic acid.When the PAA/PLA graft ratio was higher than 100%,the resulting PLA-g-PAA polymer was found dispersible in water.The pros and cons of the photo-grafting reaction were also discussed.     

Sugar‐fiber Imprinting to Generate Microgrooves on Polymeric Film Surfaces for Contact Guidance of Cells

Anisotropic surface topography is known to induce the contact guidance of cells, and facile and biocompatible approaches of the physical modification of the pertinent matrix surfaces are thus meaningful for biomaterials. Herein, we put forward a sugar‐fiber imprinting technique to generate microgrooves on hydrophobic polymers demonstrated by the poly(lactic‐co‐glycolic acid) (PLGA) films. Microgrooves were conveniently generated after removing sugar fibers simply by water. The resulting locally anisotropic microgrooves were confirmed to elongate the cells cultured on the surface.     

Synthesis and Characterization of Poly(p-phenylene benzobisoxazole)/Poly(pyridobisimidazole) Block Copolymers

Poly(p-phenylene benzobisoxazole)/poly(pyridobisimidazole) block copolymers (PBO-b-PIPD) were prepared by introducing poly(pyridobisimidazole) (PIPD) moieties into the main chains of poly(p-phenylene benzobisoxazole) (PBO) in order to enhance its photostability. PBO and copolymer fibers were directly prepared from the polymerization solutions by dry-jet wet-spinning. Chemical structures and molecular chains arrangement of the block copolymers were characterized by Fourier transform infrared (FTIR) spectroscopy, solid-state ¹³C-NMR and wide angle X-ray diffraction (WAXD). Thermal stability of the copolymers was investigated by thermogravimetric analysis (TGA) in nitrogen. Thin films of PBO and copolymers were cast from methanesulfonic acid (MSA) solutions. Both the films and fibers were exposed to UV light to determine their photostability. Changes in the chemical structures and surface morphologies of the films were characterized by FTIR spectra and scanning electronic microscopy (SEM), respectively. After UV light exposure, the retention of strength for copolymer fibers is improved compared to PBO fibers. The results revealed that copolymers suffered less photodegradation in comparison with homopolymer. The mechanism for the improved photostability of the copolymers was discussed.     

聚乙二醇-聚谷氨酸-聚丙氨酸三嵌段共聚物的合成及其胶束的pH-响应性药物控制释放

通过大分子引发剂ω-胺基-α-甲氧基聚乙二醇引发N-羧基-α-氨基环内酸酐开环聚合和酸性水解制备了一种具有pH-响应性的三嵌段共聚物聚乙二醇-聚谷氨酸-聚丙氨酸(mPEG-PLGA-PLAA).通过核磁共振、ζ-电势、动态光散射、电子显微镜等手段表征了此类三嵌段共聚物的自组装过程及所形成胶束的pH-响应性.使用圆二色谱和红外光谱,分析了胶束结构随环境pH值转变过程中聚氨基酸链段二级结构的变化.以阿霉素作为模型药物,研究了三嵌段共聚物的载药能力和在不同pH条件下的药物释放能力.在碱性条件下,PLGA链段去质子化,链段从疏水性变为亲水性,胶束中间层由于水合作用变得松散,药物释放速率增加;在酸性条件下,PLGA链段质子化,不带电荷,与阿霉素药物分子间的静电相互作用消失.同时,PLGA链段α-螺旋含量增加,形成由链内氢键维持的刚性棒状结构,将链段周围包埋的药物分子"挤出",加速了药物的释放.     

Synthesis of Functionalized Triblock Copolyesters Derived from Lactic Acid and Macrolactones for Bone Tissue Regeneration

Synthetic and functional grafts are a great alternative to conventional grafts. They can provide a physical support and the precise signaling for cells to heal damaged tissues. In this study, a novel RGD peptide end-functionalized poly(ethylene glycol)-b-poly(lactic acid)-b-poly(globalide)-b-poly(lactic acid)-b-poly(ethylene glycol) (RGD-PEG-PLA-PGl-PLA-PEG-RGD) is synthetized and used to prepare functional scaffolds. The PGl inner block is obtained by enzymatic ring-opening polymerization of globalide. The outer PLA blocks are obtained by ring-opening polymerization of both, l -lactide or a racemic mixture, initiated by the α-ω-telechelic polymacrolactone. The presence of PGl inner block enhances the toughness of PLA-based scaffolds, with an increase of the elongation at break up to 300% when the longer block of PGl is used. PLA-PGl-PLA copolymer is coupled with α-ω-telechelic PEG diacids by esterification reaction. PEGylation provides hydrophilic scaffolds as the contact angle is reduced from 114° to 74.8°. That difference improves the contact between the scaffolds and the culture media. Moreover, the scaffolds are functionalized with RGD peptides at the surface significantly enhancing the adhesion and proliferation of bone marrow-derived primary mesenchymal stem cells and MC3T3-E1 cell lines in vitro. These results place this multifunctional polymer as a great candidate for the preparation of temporary grafts.     

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     

Synthesis,Characterization and Application of Poly(lactic-co-glycolic acid) with a Mass Ratio of Lactic to Glycolic Segments of 52/48

Poly(lactic-co-glycolic acid)(PLGA) is one of the most representative degradable copolymers and promising drug carriers. In the current paper, the PLGAs with a lactic acid/ glycolic acid(LA/GA) molar ratio of 52/48 and various molecular weights were prepared by a melting method. The molecular weight, molecular weight distribution, and thermal stability were determined by ¹H NMR and thermogravimetric analysis methods. The results demonstrated that PLGAs with the fixed LA/GA molar ratio(52/48), different molecular weights, and narrow molecular weight distribution could be obtained by solely altering the reaction time. The PLGA films were prepared, and their properties including micro-structure, mechanical property, in-vitro cytotoxicity, and biodegradability were characterized. In combination with the homogeneous microstructures and mechanical properties, the drug-loading and releasing properties of PLGA_3.2 films were investigated. The results show that PLGA_3.2 film with an LA/GA molar ratio of 52/48 is a promising curcumin carrier.     

超临界CO_2发泡法制备PLGA多孔组织工程支架

利用超临界CO2(SC-CO2)发泡法制备了一系列聚(乳酸-乙醇酸)共聚物(PLGA)多孔支架材料,研究了PLGA分子量和组成、发泡过程温度、压力以及泄压速率等对泡孔尺寸及形态的影响.结果表明,随着PLGA组成中乳酸含量的增加,泡孔平均孔径增大且连通性增强;提高过程压力易形成孔径小且泡孔密度大的微孔结构材料;降低泄压速率,泡孔易合并形成大孔.聚合物处于高弹态时,较低的发泡温度易导致特殊的多面体结构大孔的形成;而当温度较高时,泡孔塌缩形成球形微孔结构,且泡孔尺寸随着温度升高而增大.SC-CO2发泡法能有效地去除有机溶剂,避免在高温条件下操作,可以实现5～500μm范围内孔径可控的PLGA多孔支架材料的制备.     

聚乳酸-聚乙二醇嵌段共聚物晶行为研究

用1H NMR, SEC, XRD和DSC对聚乳酸(PLLA)-聚乙二醇(PEG)二嵌段共聚物进行了表征. 由于共聚物中两种组分比例的不同, 表现出某组分单独结晶或两种组分共同结晶. 用DSC和POM方法, 对两组分含量相当的共聚物进行了熔体结晶行为研究, 并采用Avrami方程进行了结晶动力学计算. 用Lauritzen-Hoffmann理论对PLLA-PEG结晶机理进行了分析. 在70~94 ℃范围内, 得到成核参数Kg(POM)=5.23×105 K2. 共聚物的Kg和链折叠自由能σe都比均聚物的文献报道值高, 表明PEG链段的存在影响了PLLA的结晶, 使得其成核较均聚物困难.