Vesicle-to-spherical micelle-to-tubular nanostructure transition of monomethoxy-poly(ethylene glycol)-poly(trimethylene carbonate) diblock copolymer

Recently, we reported a temperature-sensitive biodegradable diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(trimethylene carbonate) (mPEG-PTMC; Macromolecules 2007, 40, 5519-5525). In this paper, we report the detailed morphological transition of the polymer in water as a function of polymer concentration and temperature, using cryo-transmission electron microscopy (cryo-TEM). At a low polymer concentration (0.05 wt %), the mPEG-PTMC diblock copolymers formed vesicles in water. On the other hand, vesicle-to-micelle transition was observed as the polymer concentration increased. The polymer predominantly formed micelles above 2.0 wt %. In the 2.0 wt % polymer solution, the mPEG-PTMC underwent spherical micelle-to-tubular nanostructure transition as the temperature increased from 10 to 40 degrees C, and the transition accompanied an increase in turbidity of the polymer aqueous solution due to the increase in the apparent size of the polymer aggregates. Here, we report that the morphology of vesicles, spherical micelles, and tubular nanostructures is reversibly controlled by a thermosensitive polymer of mPEG-PTMC and the variation of the morphology can be carefully traced by using cryo-TEM. This paper will not only provide an important method for morphological control of an amphiphilic polymer but also improve our understanding of a temperature-sensitive transition mechanism of the polymer.     

Suppression of cell and platelet adhesion to star-shaped 8-armed poly(ethylene glycol)-poly(L-lactide) block copolymer films

To explore the potential of a star-shaped 8-armed poly(ethylene glycol)35K-block-poly(L-lactide)37K (8-armed PEG35K-b-PLLA37K: M(n) of PEG = 35 000, M(n) of PLLA = 37 000) film as a novel bioabsorbable adhesion-prevention membrane, the water structure, surface contact angle, protein adsorption, and cell and platelet anti-adhesion properties of such a hydrated film are investigated. Based on the results, it is found that the 8-armed PEG35K-b-PLLA37K film exhibits a biologically inert surface, which is the result of a large number of PEG chains and a free water layer on the film surface. This leads to a reduction in protein absorption and cell and platelet adhesion onto the film surface. This implies that the star-shaped 8-armed PEG35K-b-PLLA37K film can be utilized as a novel bioabsorbable adhesion-prevention membrane.     

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.     

Dynamic properties of poly(styrene)-poly(ethylene oxide) diblock copolymer films at the air-water interface

The complex dynamic elasticity of monolayers of the diblock copolymer poly(styrene)-poly(ethylene oxide) at the air-water interface in the pancake, quasi-brush, and brush regimes has been studied by means of three experimental techniques--the surface transverse and longitudinal waves and the oscillating barrier method. In the pancake regime the surface viscoelastic properties in the frequency range under investigation (0.01-520 Hz) prove to be indistinguishable from the surface properties of the homopolymer PEO. Transition to the quasi-brush regime is accompanied by rather abrupt changes in both components of the surface viscoelasticity. The surface viscosity in the brush regime exceeds significantly the results calculated from the theory of D. M. A. Buzza et al. (J. Chem. Phys.109, 5008 (1998)), which takes into account the dissipation arising from the flow of solvent through the brush phase. Possible reasons of this discrepancy are discussed.     

Thermo-Responsive Hydrogels Based on Branched Poly(L-lactide)-poly(ethylene glycol) Copolymers

Summary: Branched poly(L -lactide)-poly(ethylene glycol) (PLLA-PEG) block copolymers were synthesized from trifunctional PLLA and amine functionalized methoxy poly(ethylene glycol)s. The copolymers in water formed hydrogels that showed thermo-responsive behavior. The hydrogels underwent a gel to sol transition with increasing temperature as determined with the vial tilting method and oscillatory rheology. For all copolymers, the transition temperature increased with increasing copolymer concentration. The transition temperature of corresponding branched copolymers also increased with increasing PEG molecular weight, and surprisingly decreased with increasing molecular weight of the PLLA branches. In general, the gel-sol transition is explained by disruption of micellar or aggregate interactions because of partial dehydration and shrinkage of the PEG chains. An increase in the molecular weight of the PLLA branches led to the formation of micelles and aggregates as observed with DLS at low concentrations. It is speculated that the non-uniform size distribution and possible crystallization of longer PLLA blocks may have a negative effect on the formation of micellar packing upon gelation, allowing the disruption of micellar or aggregate interactions to occur at lower temperatures. The transition temperature of the gels could be tuned closely to body temperature by varying the concentration of the solution or the molecular weight of the PEG block and the PLLA blocks, which implies that these polymers may be used as injectable systems for in-situ gel formation.     

Synthesis and characterization of poly(ethylene glycol) grafted poly(L-lactide)

Poly(ethylene glycol) grafted poly(L -lactide) was prepared by ring opening polymerization of L -lactide and epoxy-terminated poly(ethylene glycol) methyl ether (PEGME). Stannous octoate and Al(Et)₃·0.5 H₂O were tested as polymerization catalysts, and Al(Et)₃·0.5 H₂O was found to be more effective for the ring-opening of the epoxy group of the modified PEGME monomer. The synthesized polymers were characterized by NMR and the efficiency of the incorporation of epoxy-terminated PEGME in the copolymer was determined.     

Electrospun chitosan-coated fibers of poly(L-lactide) and poly(L-lactide)/poly(ethylene glycol): preparation and characterization

Fibrous poly(L-lactide) (PLLA) and bicomponent PLLA/poly(ethylene glycol) mats were prepared by electrospinning and then were coated with chitosan. The presence of chitosan coating was proved by scanning electron microscopy and by fluorescence microscopy. On contact with blood, the chitosan coating led to changes in erythrocyte shape and in their aggregation. The haemostatic activity of the mats increased with increasing chitosan content. Microbiological studies against Staphylococcus aureus revealed that the chitosan coating imparts antibacterial activity to the hybrid mats. The combined haemostatic and antibacterial activities render these novel materials suitable for wound-healing applications.     

Preparation and characterization of biodegradable nanoparticles based on amphiphilic poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) triblock copolymer

Amphiphilic triblock copolymers of poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) were directly synthesized by the ring-opening copolymerization of β-butyrolactone monomer using PEG as macroinitiator. Their structure, thermal properties and crystallization were investigated by ¹H NMR, differential scanning calorimetry (DSC) and X-ray diffraction. It was found that both PHB and PEG blocks were miscible. With the increase in the PHB block length, the triblock copolymers became amorphous because amorphous PHB block remarkably depressed the crystallization of the PEG block. Biodegradable nanoparticles with core-shell structure were prepared in aqueous solution from the amphiphilic triblock copolymers, and characterized by ¹H NMR, SEM and fluorescence. The hydrophobic PHB segments formed the central solid-like core, and stabilized by the hydrophilic PEG block. The nanoparticle size was close related to the initial concentrations of the nanoparticle dispersions and the compositions of the triblock copolymers. Moreover, the PHB-PEG-PHB nanoparticles also showed good drug loading properties, which suggested that they were very suitable as delivery vehicles for hydrophobic drugs.     

Synthesis and characterization of poly(ϵ-caprolactone)-poly(ethylene glycol) block copolymer

Poly(ϵ-caprolactone)–poly(ethylene glycol)–poly(ϵ-caprolactone) triblock copolymers (PECL) covering a wide range of poly(ethylene glycol) (PEG) lengths were synthesized with alkali metal alkoxide derivatives of poly(ethylene glycol). The effects of various factors, such as amount of the initiator, reaction time and temperature, polarity of solvent, length of PEG segment, and counterion on the polymerization were investigated. The copolymers were characterized by ¹H-NMR, IR, GPC, and DSC. It was found that THF system is superior to toluene system. The conversion of the monomer increased with increase of the initiator concentration. High molecular weight of the copolymer and high conversion of the monomer was obtained at below 30°C within 5 min. The polymerization process was studied by GPC and the coexistence of propagation and transesterification reaction was found, which leaded to relatively broad molecular weight distribution of the copolymers. © 1997 John Wiley & Sons, Inc.     

Greatly enhanced hydrolytic degradation ability of poly(L-lactide) achieved by adding poly(ethylene glycol)

Plasticized poly(L-lactide)(PLLA) materials have been applied in many fields and the microstructure performance of such materials attracts much attention of researchers. However, few reports declared the hydrolytic degradation ability of the plasticized PLLA materials. In this article, a small quantity of poly(ethylene glycol)(PEG) was introduced into PLLA, which aimed to understand the hydrolytic degradation behavior of the plasticized PLLA materials. The microstructures of the plasticized samples were comparatively investigated using scanning electron microscopy(SEM), wide angle X-ray diffraction(WAXD), differential scanning calorimetry(DSC) and Flourier transform infrared spectroscopy(FTIR), etc. The results demonstrated that PEG improved the hydrophilicity of sample surface, and the relatively high content of PEG enhanced the crystallization ability of PLLA matrix. The hydrolytic degradation measurement was carried out at 60 ℃ in an alkaline solution of pH = 12. The results demonstrated that the plasticized PLLA samples exhibited accelerated hydrolytic degradation compared with the pure PLLA sample, and the hydrolytic degradation was also dependent on the PEG content. Further results demonstrated that PEG induced the change of hydrolytic degradation mechanism possibly due to the good dissolution ability of PEG in water, which provided more paths for the penetration of water. Furthermore, the microstructure evolution of the plasticized PLLA during the hydrolytic degradation process was also investigated, and the results demonstrated the occurrence of PLLA crystallization, which was possibly contributed to the decreased hydrolytic degradation rate observed at relatively long hydrolytic degradation time. This work is of great significance and may open a new way for promoting the reclamation of PLLA waste material.     

Associative diblock copolymers of poly(ethylene glycol) and coiled-coil peptides

A series of peptides of general primary structure (VSSLESK)_n (n = 2, 3, 4, 5 and 6) were designed and synthesized by fluorenylmethyloxycarbonyl solid-phase synthesis using a convergent approach. Peptides containing 21, 28, 35 and 42 residues were modified with α-methoxy poly(ethylene glycol) (mPEG; mol. wt. 2000) by reaction of mPEG–succinimidyl carbonate with the α-amino group of the resin-attached protected peptides. The conformation and thermal stability of the peptides and of their AB block copolymers (A is the mPEG block, B the (VSSLESK)_n block) in aqueous medium were investigated by circular dichroism, size-exclusion chromatography and by analytical ultracentrifugation. The helicity of peptides increased with increasing length in a cooperative manner. The peptides and mPEG–peptides with 35 and 42 amino acid residues (block copolymers) adopted a two-stranded α-helical coiled-coil conformation in aqueous solution. The presence of the polymer chain in the diblock hybrid copolymers had no disturbing effect with respect to the stability of the α-helical peptide part in these constructs. Moreover, the thermal stability of mPEG-modified 42-peptide was substantially higher than that of the native 42-peptide. Analytical ultracentrifugation data revealed that in phosphate-buffered saline solution (25–200 μM ) the block copolymer mPEG-block-(VSSLESK)₆ ( PEG42 ) associated into stable intermolecular coiled-coil dimers.

Thermal melting profiles of peptides and mPEG–peptides at concentration 0.4 g · L⁻¹ in PBS. Molar ellipticity at 222 nm versus temperature. Heating rate 0.5 °C · min⁻¹.     

Thermogelling hydrogels of poly(ε-caprolactone-co-D,L-lactide)–poly(ethylene glycol)–poly(ε-caprolactone-co-D,L-lactide) and poly(ε-caprolactone-co-L-lactide)–poly(ethylene glycol)–poly(ε-caprolactone-co-L-lactide) aqueous solutions

Thermogelling poly(ε-caprolactone-co-D,L -lactide)–poly(ethylene glycol)–poly(ε-caprolactone-co-D,L -lactide) and poly(ε-caprolactone-co-L -lactide)–poly(ethylene glycol)–poly(ε-caprolactone-co-L -lactide) triblock copolymers were synthesized through the ring-opening polymerization of ε-caprolactone and D,L -lactide or L -lactide in the presence of poly(ethylene glycol). The polymerization reaction was carried out in 1,3,5-trimethylbenzene with Sn(Oct)₂ as the catalyst at various temperatures, and the yields were about 96%. The molecular weights and polydispersities (M_w/M_n) by gel permeation chromatography were in the ranges of 5140–6750 and 1.35–1.45, respectively. The differential scanning calorimetry results showed that the melting temperatures of the poly(ε-caprolactone) components were between 30 and 40 °C. By the subtle tuning of the chemical compositions and microstructures of these triblock copolymers, the aqueous solutions underwent sol–gel transitions as the temperature increased, with the suitable lower critical solution temperature in the range of 17–28 °C at different concentrations. Transesterification in the polymerization process generated the redistribution of sequences, which remarkably affected the sol–gel transition temperature. The amphiphilic copolymers formed micelles in aqueous solutions with a diameter of 62 nm and a critical micelle concentration of about 0.032 wt % at 20 °C. Micelles aggregated as the temperature increased, leading to gel formation. The sol–gel transition was studied, with a focus on the structure–property relationship. It is expected to have potential applications in drug delivery and tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4091–4099, 2007     

Production and characterization of poly(3-hydroxybutyrateco-3-hydroxyhexanoate)-poly(ethylene glycol) hybird copolymer with adjustable molecular weight

A novel natural-synthetic hybrid block copolymer was synthesized by Aeromonas hydrophila 4AK4 in poly(ethylene glycol)(PEG,M_n=200) modified fermentation.This hybrid biomaterial consists of the natural hydrophobic polymer poly(3-hydroxybutyrat-co-3-hydroxyhexanoate)(PHBHHx) end-capped with hydrophilic PEG,which has the increased flexibility as well as the improved thermal stability.Addition of diethylene glycol(DEG) and ethylene glycol could not result in the accumulation of hybrid block copolymer.DEG and ethylene glycol,together with PEG-200,could cause a reduction of molar mass of PHBHHx,resulting in a series of low molecular weight polymer and the reduction of the polymer yield as well as the cellular productivity.In vitro degradation of PHBHHx and PHBHHx-PEG with different molecular weight showed that the decrease of molecular weight accelerated the degradation of copolymers,but PEG modification has little effect on its degradation rate.The results in this study provided a convenient and direct method to produce a series of PHBHHx and PHBHHx-PEG materials with adjustable molecular weight and broad molecular weight distribution which will be very useful for the biomedical applications.     

Temperature-dependent aggregation and disaggregation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer in aqueous solution

Aggregation and disaggregation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, Pluronics P103 and P104, in aqueous solutions during a heating and cooling cycle were investigated by dynamic laser scattering (DLS) and 1H NMR spectroscopy. Temperature hysteresis was observed by DLS when cooling the copolymer aqueous solutions because larger aggregates existed at temperatures lower than critical micellization temperature (CMT), but no temperature differences were observed by NMR. This phenomenon was explained as the forming of water-swollen micelles at temperatures lower than CMT during the cooling process.     

Drying of films formed by ordered poly(ethylene oxide)-poly(propylene oxide) block copolymer gels

The drying of hydrogel films formed by poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers (Pluronic P105 and Pluronic L64) is investigated at various air relative humidity (RH) conditions in the range 11-94%. These amphiphilic block copolymers self-assemble to form a variety of ordered (lyotropic liquid crystalline) structures as the water content decreases. The amount of water lost increases linearly with the drying time initially (constant rate region, stage I). After this linear region, a falling rate is observed (stage II). The drying rate increases with decreasing RH, thus greatly shortening the drying time. A decrease of the initial film thickness or a decrease in the initial water content shortens the drying time; however, the drying mechanism remains the same. Analysis of the experimental data shows that the hydration level in the Pluronic hydrogel mainly determines the drying rate, rather than the type of ordered structure formed. Two distinct regions (liquid/gel and solid/crystalline) are observed in the drying isotherm for PEO-PPO block copolymers and homopolymer poly(ethylene glycol)s. A model for one-dimensional water diffusion is used to fit the experimental drying results at different RH, initial film thickness, and initial water content conditions. The model accounts for the shrinkage of the film during drying and for a water diffusion coefficient that is a function of the water concentration in the film. For the experimental conditions considered here, the Biot number (Bi) is less than unity and the drying is mainly limited by evaporation at the film surface. The diffusion model is used to obtain information for cases where Bi > 1.     

Peptide drug carrier: studies on incorporation of vasopressin into nano-associates comprising poly(ethylene glycol)-poly( -aspartic acid) block copolymer

To fabricate peptide delivery systems using polymeric drug carriers, an oligopeptide model drug, [Arg⁸]-vasopressin(AVP), was incorporated into nano-associates comprising poly(ethylene glycol)-( -aspartic acid block copolymer (PEG-P(Asp)). Incorporation of the AVP was accomplished using a dialysis method. Static light scattering measurements revealed that the acid-type and mixture-type PEG-P(Asp)s formed nano-associates independently without AVP, while the salt form PEG-P(Asp) did not. High loading of AVP into acid-type PEG-P(Asp) was observed with loading levels controlled by changing the molar ratio of drug and block copolymer. Mixture-type PEG-P(Asp) did not show high loading and the salt-type PEG-P(Asp) form did not at all. Acid-type P(Asp) homopolymer formed associates including AVP, however, it was insoluble in aqueous medium. Dynamic light scattering measurements showed that the acid-type PEG-P(Asp) associates sizes narrowly clustered around 150 nm. This finding suggests that associates of acid-type PEG-P(Asp) effectively incorporates peptides possibly via a hydrogen bonding interaction between the block copolymer and the peptide.