聚对二氧环己酮/聚乙二醇多嵌段共聚物的合成与表征

首先合成双端羟基的聚对二氧环己酮预聚物(PPDO)和双端羧基的聚乙二醇预聚物(PEG),然后以丁二酸酐/二环己基碳二亚胺(DCC)将PPDO与PEG偶联共聚,得到PPDO/PEG多嵌段共聚物.通过1H-NMR和GPC表征了聚合物的结构和分子量.采用差示扫描量热法(DSC)和热重分析(TGA)研究了共聚物的结晶性能和热稳定性.用透析法制备了共聚物纳米粒子,并用动态光散射(DLS)表征了共聚物纳米粒子的粒径及分散度,结果表明,随着共聚物亲水链段PEG含量的增加,其纳米粒子更易形成,粒子粒径随共聚物分子量增大而增大.     

A new approach to prepare high molecular weight poly(p-dioxanone) by chain-extending from dihydroxyl terminated propolymers

As poly(p-dioxanone) (PPDO) with a high molecular weight (viscosity-average molecular weight (M_ν) > 100,000 g/mol) is not easy to be obtained in a short time, a new approach has been developed to produce high molecular weight poly(p-dioxanone) (HPPDO-T) by chain-extending reaction of hydroxyl-terminated PPDO (HPPDO) prepolymers using toluene-2,4-diisocyanate (TDI) as chain extender. Here HPPDO prepolymers were synthesized via ring-opening polymerization of p-dioxanone (PDO) monomer initiated by 1,4-butanediol (BD) with Stannous octoate (SnOct₂) as catalyst. The resulting polymers, having a highest M_ν of 250,000 g/mol, were characterized by ¹H NMR, TG, DSC and WXRD. HPPDO prepolymers can react with TDI more effectively than the PPDO prepolymers initiated by mono-functional initiators, and the molecular weights of resulting chain-extended products increase several decade times in an hour comparing to the prepolymers. The chain extended products HPPDO-T have better thermal stability, and higher glass transition temperatures and lower crystallization rates than PPDO homopolymer.     

A facile approach to preparation of long-chain-branched poly(p-dioxanone)

Long-chain-branched poly(p-dioxanone)s (LCB-PPDOs) with different branch densities were prepared via the chain-extending reaction of hydroxyl group terminated linear bi-functional PPDO (2a-PPDO) and star-like tri-functional PPDO (3a-PPDO) prepolymers, which were synthesized by the ring-opening polymerization of p-dioxanone (PDO) using 1,4-butanediol (BD) and trimethylolpropane (TMP) as multi-functional initiators, respectively. The undesirable gelation was successfully depressed by adjusting the chain length and feed ratio of prepolymers. The average molecular weight between branch points (M_b) and the average number of branch per 100,000 g/mol (B_n) of LCB-PPDOs were calculated from the ¹H NMR spectra. The average number of branch ranged from 0 to 6.72 branch points per 100,000 g/mol, and the number-average molecular weights between branch points ranged from 6900 to 20,500 g/mol. The results of differential scanning calorimetry (DSC) showed that the crystallization behavior of LCB-PPDOs was changed evidently with the branch density. Small-amplitude dynamic oscillatory rheometer was used to investigate the rheological properties of the melts of LCB-PPDO including zero-shear viscosity, storage modulus, relaxation times and loss angle, which largely depended on the branch density and length of LCB-PPDOs. Therefore, the rheological behaviors of PPDO can be well-controlled via synthesizing LCB-PPDOs with the desired architectures.     

Effect of PEG on the crystallization of PPDO/PEG blends

A new biodegradable polymer system, poly(p-dioxanone) (PPDO)/poly(ethylene glycol) (PEG) blend was prepared by a solvent casting method using chloroform as a co-solvent. The PPDO/PEG blends have different weight ratios of 95/5, 90/10, 80/20 and 70/30. Crystallization of homopolymers and blends were investigated by differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD). When 5% of PEG was blended, the crystallization exothermal peaks (T_c) of PPDO increased sharply and the crystallization exothermal peaks (T_c) of PEG decreased slightly compared with the homopolymers. The crystallization rates of both components increased, and caused greater relative crystallization degree (X_t%). But when the content of PEG was more than 5%, the crystalline behaviors of blends had no more significant changes accordingly. The melting points of each sample varied little over the entire composition range in this study. The nonisothermal crystallization of PPDO homopolymer and blend (PPDO/PEG = 70/30) were also studied by DSC. The crystallization began at a higher temperature when the cooling rates were slower. The nonisothermal crystallization kinetics of blends was analyzed by Ozawa equation. The results showed that the Ozawa equation failed to describe the whole crystallization of the blend, but Mo equation could depict the nonisothermal crystallization perfectly.     

Micellization and Thermogelation of Poly(ether urethane)s Comprising Poly(ethylene glycol) and Poly(propylene glycol)

A series of multiblock poly(ether urethane)s comprising poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. Their aqueous solutions exhibited thermogelling behavior at critical gelation concentrations (CGC) ranging from 8 to 12 wt%. The composition and structural information of the copolymers were studied by GPC and ¹H NMR. The critical micellization concentration (CMC) and thermodynamic parameters for micelle formation were determined at different temperatures. The temperature response of the copolymer solutions were studied and found to be associated with the composition of the copolymers.     

Nonisothermal crystallization and melting behavior of the copolymer derived from p-dioxanone and poly(ethylene glycol)

Nonisothermal crystallization and melting behaviors of poly(p-dioxanone)(PPDO)-b-poly(ethylene glycol)(PEG) with mole ratios of 80:20 and 30:70, has been studied by differential scanning calorimeter using various cooling rates. Crystallization behavior of each crystallizable segments of the copolymer was compared with the corresponding segment of homopolymer. For a given composition, the crystallization process began at higher temperature when the slower scanning rates were used. The kinetics of the PPDO segments and the PEG segments in the copolymers under nonisothermal crystallization conditions were analyzed by Ozawa equation and also the crystallization results of the copolymer segments were compared with the corresponding homopolymers. The results showed that the Ozawa equation fails to describe the whole crystallization process of the copolymer segments along with PPDO homopolymer, but describes the crystallization behavior of the PEG homopolymer. Crystallization activation energy and absolute crystallinity values were estimated from the cooling scans (using Kissinger’s method) and fusion endotherms of the subsequent heating scans, respectively.     

Preparation, characterization and hydrolytic degradation of poly[p-dioxanone-(butylene succinate)] multiblockcopolymer

A series of poly[p-dioxanone-(butylene succinate)] (PPDOBS) copolymers were prepared from p-dioxanone (PDO), 1,4-butanediol and succinate acids through a two-step process including the initial prepolymer preparation of poly(p-dioxanone)diol (PPDO-OH) and poly(butylene succinate)diol (PBS-OH) and the following copolymerization of the two kinds of prepolymers by coupling with hexamethylene diisocyanate (HDI). The molecular structures of the prepared PPDO-OH, PBS-OH and PPDOBS were characterized by hydrogen nuclear magnetic resonance spectroscopy (¹H NMR). The crystallization of the copolymers was investigated by using differential scanning calorimetry (DSC), polarized optical microscopy (POM) and wide angle X-ray diffraction (WAXD). It has been shown that the crystallization rate and the degree of crystallization increases with the increase of the weight fraction of poly(butylene succinate) (PBS) blocks in the copolymers. In phosphate buffer solution with pH 7.4 at 37 °C for 18 weeks, the hydrolytic degradation behaviors of the copolymers were studied. The changes of retention weight, water absorption, pH value, and surface morphologies with the degradation time showed that the hydrolytic degradation rate of PPDOBS could be controlled by adjusting the weight fraction of poly(p-dioxanone) (PPDO) and PBS blocks in the copolymers. The changes of the thermal properties of PPDOBS during the degradation were also investigated by DSC.     

Photocurable biodegradable poly(ɛ-caprolactone)/poly(ethylene glycol) multiblock copolymers showing shape-memory properties

Biodegradable multiblock copolymers were synthesized by a polycondensation of poly(ɛ-caprolactone) (PCL) diols of molecular weight (MW)=3,000 and poly(ethylene glycol)s (PEG) of MW=3,000 with 4,4′-(adipoyldioxy)dicinnamic acid (CAC) dichloride as a chain extender in diphenyl ether at 180 °C for 2 h, and were characterized by GPC, ¹H-NMR, FTIR, UV, DSC, and WAXS. These photosensitive copolymers were irradiated by a 400-W high-pressure mercury lamp (λ>280 nm) from 5–60 min to form a network structure. The gel contents increased with irradiation time, and attained ca. 90% after 60 min for all copolymers. The degree of swelling in a distilled water at ambient temperature, and the rate of degradation in a phosphate buffer solution (pH 7.2) at 37 °C increased with increasing PEG components. The shape-memory tests were performed by a cyclic thermomechanical experiments for the photocured CAC/PCL/PEG (75/25) films. The film with a gel content of 57% showed the best shape-memory property with strain fixity rate of 100% and strain recovery rate of 88%.     

Amphiphilic depsipeptide‐based block copolymers as nanocarriers for controlled release of ibuprofen with doxorubicin

Well‐defined amphiphilic multiblock copolymers PDMAEMA‐b‐P(IBMD‐co‐PDO)‐b‐PEG‐b‐P(IBMD‐co‐PDO)‐b‐PDMAEMA [PDMAEMA‐PIBMD‐PPDO‐PEG], based on poly(2‐(dimethylamino)ethyl methacrylate) block (PDMAEMA), poly(3(S)‐isobutyl‐morpholine‐2,5‐dione‐co‐p‐dioxanone) block (P(IBMD‐co‐PDO)), and poly(ethylene glycol) block (PEG) were successfully synthesized by combination of ring‐opening polymerization (using 3(S)‐isobutyl‐morpholine‐2,5‐dione and p‐dioxanone initiated by hydroxyl end of PEG) and atom transfer radical polymerization (ATRP). Furthermore, all these copolymers were characterized by ¹H NMR, ¹³C NMR, Fourier transformed‐infrared, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis measurements. The degradation experiments showed that the molecular weight of PDMAEMA‐PIBMD‐PPDO‐PEG decreased along with degradation time. In addition, these copolymers could readily self‐assemble into nanosized microspheres in phosphate buffered solution. Ibuprofen (IBU) and doxorubicin (DOX) as a kind of combined model drugs were loaded into these microspheres by the combination of ionic interaction and hydrophobic effect. These copolymer microspheres exhibited high loading capacity (LC, up to 26.88%), encapsulation efficiency (EE, up to 61.29%), and sustained release behavior of IBU–DOX in phosphate buffered solution. The results of transmission electron microscopy and dynamic light scattering showed that the microspheres were well‐defined uniform spherical particles with average diameter less than 120 nm. Therefore, it can be envisaged that these copolymer systems are promising candidates for controlled release application. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3213–3226     

A novel aromatic–aliphatic copolyester consisting of poly(1,4‐dioxan‐2‐one) and poly(ethylene‐co‐1,6‐hexene terephthalate): Preparation,thermal, and mechanical properties

A novel multiblock aromatic–aliphatic copolyester poly(ethylene‐co‐1,6‐hexene terephthalate)‐copoly(1,4‐dioxan‐2‐one) (PEHT‐PPDO) was successfully synthesized via the chain‐extension reaction of dihydroxyl teminated poly(ethylene‐co‐hexane terephthalate) (PEHT‐OH) with dihydroxyl teminated poly(1,4‐dioxan‐2‐one) (PPDO‐OH) prepolymers, using toluene‐2,4‐diisocyanate as a chain extender. To produce PEHT‐OH prepolymer with an appropriate melting point which can match the reaction temperature of PEHT‐OH prepolymer with PPDO‐OH prepolymer, 1,6‐hexanediol was used to disturb the regularity of poly(ethylene terephthalate) segments. The chemical structures and molecular weights of PEHT‐PPDO copolymers were characterized by ¹H NMR, FTIR, and GPC. The DSC data showed that PPDO‐OH segments were miscible well with PEHT‐OH segments in amorphous state and that the crystallization of copolyester was predominantly contributed by PPDO segments. The TGA results indicated that the thermal stability of PEHT‐PPDO was improved comparing with PPDO homopolymer. The novel aromatic–aliphatic copolyesters have good mechanical properties and could find applications in the field of biodegradable polymer materials. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2828–2837, 2010     

Synthesis of poly(p-dioxanone)-based block copolymers in supercritical carbon dioxide

Poly(p-dioxanone)–poly(ethylene glycol)–poly(p-dioxanone) triblock copolymers (PPDO–PEG–PPDO) were first synthesized by suspension ring-opening polymerization (ROP) of p-dioxanone (PDO) in supercritical carbon dioxide (scCO₂) using different molecular weights (2–10 K) of poly(ethylene glycol) (PEG) as macroinitiators. White and fine flow powders were successfully obtained when the molecular weight of PEG was below 6 K and its feed content below 20 wt.%. The ¹H nuclear magnetic resonance (NMR) result indicated the formation of PPDO–PEG–PPDO block structure even in a confined polymerized environment of particles. All the powderous samples contained irregular shaped particles that were observed by scanning electron microscope (SEM). Except for the copolymer with 10 wt.% PEG10K feed content, the mean particle sizes of other powderous samples showed identical values close to 15 μm. This fact was in agreement with the crystallinity of PPDO in the copolymers measured by differential scanning calorimetry (DSC). The water absorption of these copolymers was also measured, and as compared with PPDO homopolymer, the introduction of PEG increased the water absorption of the copolymers. The green and environmentally friendly method disclosed in this work is attractive to directly synthesize biodegradable polymeric particles with potential biomedical applications.     

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.     

Multiblock copolymers composed of poly(butylene succinate) and poly(1,2-propylene succinate): Effect of molar ratio of diisocyanate to polyester-diols on crosslink densities, thermal properties, mechanical properties and biodegradability

In order to study the relationship between structure and properties, multiblock copolymers composed of poly(butylene succinate) (PBS) and poly (1,2-propylene succinate) (PPSu) have been synthesized by chain-extension at various molar ratios of hexamethylene diisocyanate (HDI) to polyester-diols, which have been abbreviated as R-values in this paper. Molecular weights of soluble fractions, gel fractions and crosslink densities have been determined. Thermal properties, mechanical properties and biodegradability have been studied and correlated with R-values. Crystallization of copolymers becomes difficult with increasing R-value. Tensile strength, flexural strength and flexural modulus tend to increase with increasing R-value up to 1.2, and vary little when R-value increases from 1.2 to 1.3, then decrease with further increase in R-value. Impact strength achieves a maximum value at R-value of 1.3. Biodegradation rate reaches a minimum value when R-value is 1.1. Biodegradation has been studied systematically by attenuated total reflectance Fourier transform infrared (ATR-FTIR), ¹H NMR and SEM.     

聚对二氧环己酮/聚乙二醇两亲性聚合物共网络的合成与表征

以辛酸亚锡为催化剂,季戊四醇(PTOL)为引发剂,引发对二氧环己酮(PDO)单体开环聚合,合成了以PTOL为核的四臂聚对二氧环己酮(4s-PPDO).通过直接将4s-PPDO预聚物和聚乙二醇(PEG)于熔点以上、惰性气体保护下与偶联剂甲苯二异氰酸酯(TDI)交联共聚得到聚对二氧环己酮/聚乙二醇(PPDO-b-PEG)两亲性共网络聚合物(PPDO-PEG APCNs).研究了两亲性聚合物共网络结构、配比组成、溶剂种类等对聚合物溶胀率的影响,结果表明APCNs在不同类型的溶剂中表现出不同的溶胀行为,可以通过调节偶联剂的用量及PPDO/PEG的投料比来满足不同的实际需求.通过示差扫描量热分析(DSC)详细研究APCNs的结晶性能,证实交联反应降低APCNs的结晶度和结晶尺寸.     

Self-assembling of biocompatible BAB amphiphilic triblock copolymers PLL(Z)-PEG-PLL(Z) in aqueous medium

A novel biocompatible BAB amphiphilic triblock copolymers which consist of poly(ethylene glycol) (PEG) and poly(ε-benzyloxycarbonyl l-Lysine) (PLL(Z)) were synthesized by anion ring opening polymerization of N-carboxyanhydride of ε-benzyloxycarbonyl-l-Lysine (l-Lys(z)-NCA) using α-amino-ω-amino-poly(ethylene glycol) as initiator in DMF. The block copolymers were characterized by IR, ¹H-NMR, GPC, DSC. The results showed that the block copolymers were of narrow molecular distribution and well defined structure. The self-assembled behaviors of block copolymers in aqueous medium were investigated. The effects of various factors, such as cosolvents, initial concentration, temperature, annealing time and times of frozen-thaw cycle etc., on the aggregate morphologies were investigated by transmission electron microscopy (TEM). Different morphological aggregates such as sphere, rod and vesicle etc. could be obtained at controlled conditions, at the same time, a novel helical aggregate was observed. These regular nanometer structures have potential applications in biomedicine due to the biocompatibility of two blocks.     

Enhanced thermal stability of poly(1,4-dioxan-2-one) in melt by adding a chelator

Thermal stability of poly(p-dioxanone) (PPDO) was investigated isothermally and non-isothermally under air atmosphere using thermogravimetry (TG). The addition of 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (PMBP) could enhance successfully the thermal stability of PPDO compared with those of as-prepared and purified PPDO at temperature below about 230 °C. The activation energies for thermal degradation (ΔE_td) were evaluated at different weight loss values from TG data using the procedure recommended by MacCallum et al. The ΔE_td values of as-prepared PPDO, purified PPDO and PPDO containing 1.0 wt% PMBP were in the ranges of 20-50, 35-60, and 56-88 kJ mol⁻¹, respectively, when they were evaluated at weight loss values of 10-80%. The remaining weights increase with the amounts of PMBP added up to 1.5 wt%. The mechanism for the enhanced thermal stability of PPDO was discussed.     

Quadruple click reactions for the synthesis of cysteine‐terminated linear multiblock copolymers

Synthesis of cysteine‐terminated linear polystyrene (PS)‐b‐poly(ε‐caprolactone) (PCL)‐b‐poly(methyl methacrylate) (PMMA)/or poly(tert‐butyl acrylate)(PtBA)‐b‐poly(ethylene glycol) (PEG) copolymers was carried out using sequential quadruple click reactions including thiol‐ene, copper‐catalyzed azide–alkyne cycloaddition (CuAAC), Diels–Alder, and nitroxide radical coupling (NRC) reactions. N‐acetyl‐L ‐cysteine methyl ester was first clicked with α‐allyl‐ω‐azide‐terminated PS via thiol‐ene reaction to create α‐cysteine‐ω‐azide‐terminated PS. Subsequent CuAAC reaction with PCL, followed by the introduction of the PMMA/or PtBA and PEG blocks via Diels–Alder and NRC, respectively, yielded final cysteine‐terminated multiblock copolymers. By ¹H NMR spectroscopy, the DP_ns of the blocks in the final multiblock copolymers were found to be close to those of the related polymer precursors, indicating that highly efficient click reactions occurred for polymer–polymer coupling. Successful quadruple click reactions were also confirmed by gel permeation chromatography. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

POLY(p-DIOXANONE) AND ITS COPOLYMERS

ABSTRACT

This paper reviews the synthesis, properties, and applications of biodegradable polymer, poly(p-dioxanone) (PPDO), and its copolymers. Recent progress in ring-opening polymerization of p-dioxanone employing several effective catalysts is described. Properties of PPDO are given. The copolymers based on PPDO are also discussed.     

聚丙交酯/聚乙二醇多嵌段共聚物的合成及其性能

聚丙交酯 (ＰＬＬＡ)由于具有良好的生物降解性和生物相容性 ,在医学领域已经得到了广泛的临床应用 ,近来又被制备成细胞支架大量应用于组织工程中[1,2 ] ,但由于其疏水性而造成细胞亲和性不好 .聚乙二醇 (ＰＥＧ)具有良好的亲水性 ,良好的生物相容性 ,但是ＰＥＧ是非降解性的 ,只有低分子量的ＰＥＧ可以被吞噬细胞所吞噬或透过肾滤膜而排出体外 ,因此 ,低分子量的ＰＥＧ常被用来与丙交酯 (Ｌ ＬＡ)共聚以改善ＰＬＬＡ支架的亲水性 .聚丙交酯 聚乙二醇共聚物 (ＰＬＥ)的三嵌段及两嵌段共聚物的合成及其性能的研究已被广泛报道[3～ 5] .研究…     

Amphiphilic biodegradable poly(CL-b-PEG-b-CL) triblock copolymers prepared by novel rare earth complex: Synthesis and crystallization properties

Amphiphilic biodegradable poly(CL-b-PEG-b-CL) triblock copolymers have been successfully prepared by the ring-opening polymerization of ε-caprolactone (CL) employing yttrium tris(2,6-di-tert-butyl-4-methylphenolate) [Y(DBMP)₃] as catalyst and double-hydroxyl capped PEGs (DHPEG) as macro-initiator. The triblock architecture, molecular weight, thermal and crystallization properties of the copolymers were characterized by NMR spectra, SEC, DSC and WAXD analyses. The isothermal crystallization behavior of the copolymers was investigated by POM analysis in detail, which is greatly influenced by the length of PCL and PEG blocks. On the POM micrograph of PEG_10,000-(PCL₈₆₀₀)₂, a unique morphology of concentric spherulites was observed due to the sequent crystallization of the PCL and PEG blocks.