Synthesis and characterization of poly(L‐lactide)‐poly(ethylene glycol) multiblock copolymers

Poly(L‐lactide)‐poly(ethylene glycol) multiblock copolymers with predetermined block lengths were synthesized by polycondensation of PLA diols and PEG diacids. The reaction was carried out under mild conditions, using dicyclohexylcarbodiimide as the coupling agent and dimethylaminopyridine as the catalyst. The resulting copolymers were characterized by various analytical techniques, such as GPC, viscometry, ¹H‐NMR, FTIR, DSC, X‐ray diffractometry, and contact angle measurement. The results indicated that these copolymers presented outstanding properties pertinent to biomedical use, including better miscibility between the two components, low crystallinity, and hydrophilicity. Moreover, the properties of the copolymers can be modulated by adjusting the block length of the two components or the reaction conditions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1729–1736, 2002; DOI 10.1002/app.10580     

Crystallization behavior of biodegradable amphiphilic poly(ethylene glycol)‐poly(L‐lactide) block copolymers

Poly(ethylene glycol)‐poly(L ‐lactide) diblock and triblock copolymers were prepared by ring‐opening polymerization of L ‐lactide with poly(ethylene glycol) methyl ether or with poly(ethylene glycol) in the presence of stannous octoate. Molecular weight, thermal properties, and crystalline structure of block copolymers were analyzed by ¹H‐NMR, FTIR, GPC, DSC, and wide‐angle X‐ray diffraction (WAXD). The composition of the block copolymer was found to be comparable to those of the reactants. Each block of the PEG–PLLA copolymer was phase separated at room temperature, as determined by DSC and WAXD. For the asymmetric block copolymers, the crystallization of one block influenced much the crystalline structure of the other block that was chemically connected to it. Time‐resolved WAXD analyses also showed the crystallization of the PLLA block became retarded due to the presence of the PEG block. According to the biodegradability test using the activated sludge, PEG–PLLA block copolymer degraded much faster than PLLA homopolymers of the same molecular weight. © 1999 John Wiley amp; Sons, Inc. J Appl Polym Sci 72: 341–348, 1999     

Synthesis and characterization of ABA type tri‐block copolymers derived from p‐dioxanone,L‐lactide and poly(ethylene glycol)

A series of triblock co‐polymers, consisting of a poly(ethylene glycol) (PEG) central block joined to two blocks of random p‐dioxanone‐co‐L ‐lactide copolymers were synthesized by ring‐opening polymerization of p‐dioxanone (PDO) and L ‐lactide (LLA) initiated by PEG in the presence of stannous 2‐ethylhexanoate catalyst. The resulting copolymers were characterized by various techniques including ¹H and ¹³C NMR and FTIR spectroscopies, gel permeation chromatography, inherent viscosity, wide‐angle X‐ray diffractometry (WAXD) and differential scanning calorimetry (DSC). The conversion of PDO and L ‐lactide into the polymer was studied various mole ratios and at different polymerization temperature from ¹H NMR spectra. Results of WAXD and DSC showed that the crystallinity of PEG macroinitiator was greatly influenced by the composition of PDO and L ‐lactide in the copolymer. The triblock copolymers with low molecular weight were soluble in water at below room temperature. © 2003 Society of Chemical Industry     

Aging of poly(lactide)/poly(ethylene glycol) blends. Part 2. Poly(lactide) with high stereoregularity

Blending poly(ethylene glycol) (PEG) with poly(lactide) (PLA) decreases the T_g and improves the mechanical properties. The blends have lower modulus and increased fracture strain compared to PLA. However, the blends become increasingly rigid over time at ambient conditions. Previously, it was demonstrated that a PLA of lower stereoregularity was miscible with up to 30 wt% PEG. Aging was due to slow crystallization of PEG from the homogeneous amorphous blend. Crystallization of PEG depleted the amorphous phase of PEG and gradually increased the T_g until aging essentially ceased when T_g of the amorphous phase reached the aging temperature. In the present study, this aging mechanism was tested with a crystallizable PLA of higher stereoregularity. Changes in thermal transitions, solid state structure, and mechanical properties were examined over time. Blends with up to 20 wt% PEG were miscible. Blends with 30 wt% PEG could be quenched from the melt to the homogenous amorphous glass. However, this composition phase separated at ambient temperature with little or no crystallization. Changes in mechanical properties during phase separation reflected increasing rigidity of the continuous PLA-rich phase as it became richer in PLA. Construction of a phase diagram for blends of higher stereoregular PLA with PEG was attempted.     

Aging of poly(lactide)/poly(ethylene glycol) blends. Part 1. Poly(lactide) with low stereoregularity

Poly(lactide) (PLA) is rapidly gaining interest as a biodegradable thermoplastic for general usage in degradable disposables. To improve mechanical properties, a PLA with low stereoregularity was blended with polyethylene glycol (PEG). Blends with up to 30 wt% PEG were miscible at ambient temperature. Blending with PEG significantly decreased the T_g, decreased the modulus and increased the fracture strain of PLA. However, the PLA/PEG 70/30 blend became increasingly rigid over time at ambient conditions. The mechanism of aging primarily under ambient conditions of temperature and humidity was studied. Changes in mechanical properties, thermal transitions and solid state morphology were examined over time. Aging was caused by slow crystallization of PEG. Crystallization of PEG depleted the amorphous phase of PEG and gradually increased the T_g. As T_g approached the aging temperature, reduced molecular diffusivity slowed the crystallization rate dramatically. Aging essentially ceased when T_g of the amorphous phase reached the aging temperature. The increase in matrix T_g and the reinforcing effect of the crystals produced a change in mechanical properties from elastomer-like to thermoplastic-like.     

Methoxy poly(ethylene glycol)‐block‐poly(D,L‐lactic acid) copolymer nanoparticles as carriers for transdermal drug delivery

This work evaluates the transdermal drug delivery properties of amphiphilic copolymer self‐assembled nanoparticles by skin penetration experiments in vitro. Paclitaxel‐loaded methoxy poly(ethylene glycol)‐block‐poly(D ,L ‐lactic acid) diblock copolymer nanoparticles (PNPs) were prepared by a solid dispersion technique and were applied to the surface of excised full‐thickness rat skin in Franz diffusion cells. HPLC, transmission electron microscopy, Fourier transform infrared spectroscopy and ¹H NMR were used to assay the receptor fluid. The results show that the amphiphilic copolymer nanoparticles with the entrapped paclitaxel are able to penetrate rat skin. Ethanol can improve the delivery of PNPs and increase the cumulative amount of paclitaxel in the receptor fluid by 3 times. Fluorescence microscopy measurements indicate that the PNPs can penetrate the skin not only via appendage routes including sweat ducts and hair follicles but also via epidermal routes. Copyright © 2007 Society of Chemical Industry     

Crystallization and phase separation in blends of high stereoregular poly(lactide) with poly(ethylene glycol)

The effect of cooling rate on crystallization and subsequent aging of high stereoregular poly(lactide) (PLA) blended with poly(ethylene glycol) (PEG) was studied by thermal analysis and by direct observation of the solid state structure with atomic force microscopy (AFM). Blending with PEG accelerated crystallization of PLA. When a PLA/PEG 70/30 (wt/wt) blend was slowly cooled from the melt, PLA crystallized first as large spherulites followed by crystallization of PEG. The extent of PLA crystallization depended on the cooling rate, however, for a given blend composition the PEG crystallinity was proportional to PLA crystallinity. The partially crystallized blend obtained with a cooling rate of 30 °C min⁻¹ consisted of large spherulites dispersed in a homogeneous matrix. The blend was not stable at ambient temperature. With time, epitaxial crystallization of PEG on the edges of the spherulites depleted the surrounding region of PEG, which created a vitrified region surrounding the spherulites. Further from the spherulites, the homogeneous amorphous phase underwent phase separation with formation of a more rigid PLA-rich phase and a less-rigid PEG-rich phase. Decreasing the amount of PEG in the blend decreased the crystallization rate of PLA and increased the nucleation density. The amount of PLA crystallinity did not depend on blend composition, however, PEG crystallinity decreased to the extent that PEG did not crystallize in a PLA/PEG 90/10 (wt/wt) blend.     

Formation of honeycomb films from poly(L‐lactide)‐block‐poly(ethylene glycol) via water‐droplet templating

The fabrication of honeycomb‐patterned films from amphiphilic poly(L ‐lactide)‐block‐poly(ethylene glycol) (PLEG) in a high‐humidity atmosphere is reported. The influence of the solution concentration on pattern formation was investigated. Moreover, by comparing the different conditions of fabricating regular structures between PLEG and poly(phenylene oxide), the mechanism of the regular pattern formation was studied. Finally, by adding sodium dodecylsulfate to a concentrated solution of 1 g L^?1 PLEG? CHCl₃ which otherwise could not form regular pores, we found that regular pores could be obtained. The PLEG honeycomb films are expected to be of use in cell culture, tissue engineering and many other areas. Copyright © 2007 Society of Chemical Industry     

Synthesis and characterization of star‐shaped poly(ethylene glycol)‐block‐poly(L‐lactic acid) copolymers by melt polycondensation

Compared with linear diblock or triblock poly(ethylene glycol)‐block‐poly(L ‐lactic acid) copolymer (PEG‐b‐PLLA), star‐shaped PEG‐b‐PLLA (sPEG‐b‐PLLA) copolymers exhibit smaller hydrodynamic radius and lower viscosity and are expected to display peculiar morphologies, thermal properties, and degradation profiles. Compared with the synthesis routine of PEG‐b‐PLLA form lactide and PEG, the traditional synthesis routine from LA and PEG were suffered by the low reaction efficiency, low purity, lower molecular weight, and wide molecular weight distribution. In this article, multiarm sPEG‐b‐PLLA copolymer was prepared from multiarm sPEG and L ‐lactic acid (LLA using an improved method of melt polycondensation, in which two types of sPEG, that is, sPEG₁ (four arm, Mn = 4300) and sPEG₂ (three arm, Mn = 3200) were chosen as the core. It was found the molecular weight of sPEG‐b‐PLLA could be strongly affected by the purity of LLA and sPEGs, and the purification technology of vacuum dewater and vacuum distillation could help to remove most of the impurities in commercial available LLA. The polymers, including sPEG and sPEG‐b‐PLLA with varied core (sPEG₁ and sPEG₂) and LLA/sPEG feeding ratios, were characterized and confirmed by ¹H‐NMR and ¹³C‐NMR spectroscopy, Fourier transform infrared spectroscopy (FT‐IR) and gel permeation chromatography, which showed that the terminal hydroxyl group in each arm of sPEGs had reacted with LLA to form sPEG‐b‐PLLA copolymers with fairly narrow molecular weight distribution. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

聚乙二醇/聚己内酯三嵌段共聚物的合成与表征

以甲苯二异氰酸酯 (TDI)为偶联剂 ,合成了聚乙二醇 (PEG) /聚己内酯 (PCL)两亲性三嵌段共聚物 (PEG-b-PCL -b -PEG ,PECL) ,采用IR、1 H-NMR、DSC和WAXD分析和研究了PECL的结构与性能。实验结果表明 ,PECL的结构和组成与设计相一致 ,结晶度和熔点均低于均聚物 ,且随着PECL中PCL嵌段含量的增加 ,PCL嵌段熔点升高。透射电镜照片显示PECL纳米粒呈核 /壳结构的球形。     

Surfactant‐free nanoparticles of poly(DL‐lactide‐co‐glycolide) prepared with poly(L‐lactide)/ poly(ethylene glycol)

Surfactant‐free nanoparticles of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles were prepared with or without poly(L ‐lactide)‐poly(ethylene oxide) (LE) diblock copolymer (abbreviated as PLGA/LE and PLGA nanoparticles) by dialysis method. LE diblock copolymer was used to make PLGA nanoparticles to alternate conventional surfactant. The size of PLGA and PLGA/LE nanoparticles was 295.3 ± 171.3 and 307.6 ± 27.2 nm, respectively, suggesting LE diblock copolymer might be coated onto the surface of nanoparticles. Observation of scanning electron microscope (SEM) showed that PLGA/LE nanoparticles have spherical shapes ranging ～ 200–500 nm. In ¹H‐NMR study, characteristic peaks of the methyl protons of PLGA disappeared in D₂O, whereas characteristic peaks of the methyl proton of both PEG and PLGA were shown in both CDCl₃ and D₂O, indicating that LE diblock copolymer coated on the surface of the PLGA nanoparticles. The higher the initial content of drug, the higher the drug contents and the lower the loading efficiency. PLGA/LE nanoparticles at higher drug contents resulted in slower adriamycin·HCl (ADR) release rate than that of lower drug contents. Also, slower release rate of ADR was achieved by entrapped into the PLGA/LE nanoparticles, whereas LE polymeric micelles showed rapid ADR release. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1116–1123, 2003     

Preparation of core–shell poly(acrylic acid)/polystyrene/SiO2 hybrid microspheres

Core–shell poly(acrylic acid)/polystyrene/SiO₂ (PAA/PS/SiO₂) hybrid microspheres were prepared by dispersion polymerization with three stages in ethanol and ethyl acetate mixture medium. Using vinyltriethoxysilane (VTEOS) as silane agent, functional silica particles structured vinyl groups on surfaces were prepared by hydrolysis and polycondensation of tetraethoxysilane and VTEOS in core stage. Then, the silica particles were used as seeds to copolymerize with styrene and acrylic acid sequentially in shell stage I and stage II to form PAA/PS/SiO₂ hybrid microspheres. Transmission electron microscope results show that most PAA/PS/SiO₂ hybrid microspheres are about 40 nm in diameter, and the silica cores are about 15 nm in diameter, which covered with a layer of PS about 7.5‐nm thick and a layer of PAA about 5‐nm thick. This core–shell structure is also conformed by Fourier transform infrared spectroscopy, X‐ray photoelectron spectroscopy, and differential scanning calorimetry. FTIR results show that silica core, PS shell, and PAA outermost shell are bonded by covalents. In the core–shell PAA/PS/SiO₂ hybrid microsphere, the silica core is rigidity, and the PAA outermost shell is polarity, while the PS layer may work as lubricant owning to its superior processing rheological property in polymer blending. These core–shell PAA/PS/SiO₂ hybrid microspheres have potential as new materials for polar polymer modification. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 1729–1733, 2006     

Preparation and characterization of enalapril maleate–loaded nanoparticles using amphiphilic diblock copolymers

Nanoparticles with the dimensions of circa 50 nm prepared from the micellar aggregation of diblock copolymers of poly(ethylene oxide) and polycaprolactone (PEO–b–PCL) were explored as a parenteral carrier system for water‐soluble organic drugs in salt form. Enalapril maleate (EPM), developed for hypertension and congestive heart failure, was used as a model drug. The nanoparticles from three block copolymers with compositions of 5k–7.5k, 5k–5k, and 5k–2.5k (PEO–b–PCL) exhibited drug‐loading efficiency of 38%, 47%, and 26%, respectively, for an equivalent amount of EPM in a 1% (w/v) micelle solution. Particularly, 5k–5k micelles could be incorporated with the model drug up to 47% (w/w) of polymer. Furthermore, these nanoparticles possess drug‐retaining capability at 25°C or below even after free EPM was eliminated from the aqueous phase by dialysis. A temperature‐responsive release behavior was displayed upon heating to the physiological temperature, 37°C. Drug release from the micelles proceeded in a fairly linear fashion for a duration of about 4–7 days, depending on the composition of the block copolymers. Daily average fractional release was consistent regardless of drug contents in the nanoparticles. In a preliminary animal toxicity test the EPM‐loaded micelle solutions were intravenously administered to mice of the ICR strain through the tail vein. The animal subjects received 0.7 mL of EPM micelle solution up to six times and showed normal weight gain and food consumption. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 2856–2867, 1999     

Biodegradability of poly(ethylene terephthalate) copolymers with poly(ethylene glycol)s and poly(tetramethylene glycol)

Poly(ethylene terephthalate) copolymers were prepared by melt polycondensation of dimethyl terephthalate and excess ethylene glycol with 10–40mol% (in feed) of poly(ethylene glycol) (E) and poly(tetramethylene glycol) (B), with molecular weight (MW) of E and B 200–7500 and 1000, respectively. The reduced specific viscosity of copolymers increased with increasing MW and content of polyglycol comonomer. The temperature of melting (T_m), cold crystallization and glass transition (T_g) decreased with the copolymerization. T_m depression of copolymers suggested that the E series copolymers are the block type at higher content of the comonomer. T_g was decreased below room temperature by the copolymerization, which affected the crystallinity and the density of copolymer films. Water absorption increased with increasing content of comonomer, and the increase was much higher for E1000 series films than B1000 series films. The biodegradability was estimated by weight loss of copolymer films in buffer solution with and without a lipase at 37°C. The weight loss was enhanced a little by the presence of a lipase, and increased abruptly at higher comonomer content, which was correlated to the water absorption and the concentration of ester linkages between PET and PEG segments. The weight loss of B series films was much lower than that of E series films. The abrupt increase of the weight loss by alkaline hydrolysis is almost consistent with that by biodegradation.     

Interfacially initiated microemulsion copolymerization: One‐stage preparation of poly(n‐butyl methacrylate)–poly(N‐vinyl pyrrolidone) core–shell nanoparticles

Interfacially initiated microemulsion copolymerizations of n‐butyl methacrylate (BMA) and N‐vinyl pyrrolidone (NVP) by the redox initiation couple of benzoyl peroxide and ferrous sulfate were carried out with Tween 80 and n‐butanol as the surfactant and cosurfactant, respectively. Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy were recorded to analyze the chemical composition of the latex particles. Transmission electron microscopy was used to observe the particle morphology and dynamic light scattering to determine the particle size. The results demonstrated that interfacially initiated microemulsion polymerization prompted the copolymerization of the water‐soluble NVP monomer with the oil‐soluble BMA monomer to form core–shell nanoparticles. The influence of the surfactant concentration, BMA amount, and temperature on the particle size and polymerization rate was investigated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 3751–3757, 2006     

Synthesis and characterization of novel block copolymer from trans‐4‐hydroxy‐L‐proline and poly(ethylene glycol)

A series of novel ABA‐type block copolymers were synthesized by polymerization of trans‐4‐hydroxy‐L ‐proline (HyP) in the presence of various molecular weight poly(ethylene glycol)s (PEGs), a bifunctional OH‐terminated PEG using stannous octoate as catalyst. The optimal reaction conditions for the synthesis of the copolymers were obtained with 5 wt % stannous octoate at 140°C under vacuum (20 mmHg) for 24 h. The synthesized copolymers were characterized by IR spectroohotometry, proton nuclear magnetic resonance, differential scanning calorimetry, and Ubbelohde viscometer. The glass transition temperature (T_g) of the copolymers shifted to significantly higher temperature with increasing the number average degree of polymerization and HyP/PEO molar ratio. In contrast, the melting temperature (T_m) decreased with increasing the HyP/PEO molar ratio. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1581–1587, 2001     

ABA triblock copolymers from poly(p‐dioxanone) and poly(ethylene glycol)

Poly(p‐dioxanone)–poly(ethylene glycol)–poly(p‐dioxanone) ABA triblock copolymers (PEDO) were synthesized by ring‐opening polymerization from p‐dioxanone using poly(ethylene glycol) (PEG) with different molecular weights as macroinitiators in N₂ atmosphere. The copolymer was characterized by ¹H NMR spectroscope. The thermal behavior, crystallization, and thermal stability of these copolymers were investigated by differential scanning calorimetry and thermogravimetric measurements. The water absorption of these copolymers was also measured. The results indicated that the content and length of PEG chain have a greater effect on the properties of copolymers. This kind of biodegradable copolymer will find a potential application in biomedical materials. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102:1092–1097, 2006     

Electrospun poly(L‐lactide)/poly(ε‐caprolactone) blend fibers and their cellular response to adipose‐derived stem cells

Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue‐engineering applications. In this study, electrospun poly(L ‐lactide)/poly(ε‐caprolactone) (PLLA/PCL) blend fibrous membranes with defect‐free morphology and uniform diameter were optimally prepared by a 1 : 1 ratio of PLLA/PCL blend under a solution concentration of 10 wt %, an applied voltage of 20 kV, and a tip‐to‐collector distance of 15 cm. The fibrous membranes also showed a porous structure and high ductility. Because of the rapid solidification of polymer solution during electrospinning, the crystallinity of electrospun PLLA/PCL blend fibers was much lower than that of the PLLA/PCL blend cast film. To obtain an initial understanding of biocompatibility, adipose‐derived stem cells (ADSCs) were used as seed cells to assess the cellular response, including morphology, proliferation, viability, attachment, and multilineage differentiation on the PLLA/PCL blend fibrous scaffold. Because of the good biocompatibility and nontoxic effect on ADSCs, the PLLA/PCL blend electrospun fibrous membrane provided a high‐performance scaffold for feasible application in tissue engineering using ADSCs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Crystallization kinetics of poly(L‐lactide)/carbonated hydroxyapatite nanocomposite microspheres

Microspheres consisting of carbonated hydroxyapatite (CHAp) nanoparticles and poly(L ‐lactide) (PLLA) have been fabricated for use in the construction of osetoconductive bone tissue engineering scaffolds by selective laser sintering (SLS). In SLS, PLLA polymer melts and crystallizes. It is therefore necessary to study the crystallization kinetics of PLLA/CHAp nanocomposites. The effects of 10 wt% CHAp nanoparticles on the isothermal and nonisothermal crystallization behavior of PLLA matrix were studied, using neat PLLA for comparisons. The Avrami equation was successfully applied for the analysis of isothermal crystallization kinetics. Using the Lauritzen‐Hoffman theory, the transition temperature from crystallization Regime II to Regime III was found to be around 120°C for both neat PLLA and PLLA/CHAp nanocomposite. The combined Avrami‐Ozawa equation was used to analyze the nonisothermal crystallization process, and it was found that the Ozawa exponent was equal to the Avrami exponent for neat PLLA and PLLA/CHAp nanocomposite, respectively. The effective activation energy as a function of the relative crystallinity and temperature for neat PLLA and PLLA/CHAp nanocomposite under the nonisothermal crystallization condition was obtained by using the Friedman differential isoconversion method. The Lauritzen‐Hoffman parameters were also determined from the nonisothermal crystallization data by using the Vyazovkin‐Sbirrazzuoli equation. CHAp nanoparticles in the composite acted as an efficient nucleating agent, enhancing the nucleation rate but at the same time reducing the spherulite growth rate. This investigation has provided significant insights into the crystallization behavior of PLLA/CHAp nanocomposites, and the results obtained are very useful for making good quality PLLA/CHAp scaffolds through SLS. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis and hydrophilicity of poly(butylene 2,6‐naphthalate)/poly(ethylene glycol) copolymers

Poly(butylene 2,6‐naphthalate) (PBN)/poly(ethylene glycol) (PEG) copolymers were synthesized by the two‐step melt copolymerization process of dimethyl‐2,6‐naphthalenedicarboxylate (2,6‐NDC) with 1,4‐butanediol (BD) and PEG. The copolymers produced had different PEG molecular weights and contents. The structures, thermal properties, and hydrophilicities of these copolymers were studied by ¹H NMR, DSC, TGA, and by contact angle and moisture content measurements. In particular, the intrinsic viscosities of PBN/PEG copolymers increased with increasing PEG molecular weights, but the melting temperatures (T_m)_, the cold crystallization temperatures (T_cc)_, and the heat of fusion (ΔH_f) values of PBN/PEG copolymers decreased on increasing PEG contents or molecular weights. The thermal stabilities of the copolymers were unaffected by PEG content or molecular weight. Hydrophilicities as determined by contact angle and moisture content measurements were found to be significantly increased on increasing PEG contents and molecular weights. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2677–2683, 2006