Biodegradable heparin-loaded microspheres: carrier molecular composition and microsphere structure

Microspheres of amphiphilic triblock polymers PLLA-PEG-PLLA were investigated as carriers for heparin delivery. Two series of PLLA-PEG-PLLA triblock were synthesized and prepared into microspheres with heparin loaded. The microspheres were hollow and the surface morphology varied from smooth to porous. The pore size increased with increasing PEG content. The microsphere size distribution showed that higher PEG content increased the average microsphere size. The release rate of heparin was closely related to the surface morphology of the microspheres. DSC spectra showed that both cold crystalline temperature (Tc) and crystalline melting temperature (Tm) of heparin-loaded microspheres were related to the copolymer composition and the Tc was lower than those of corresponding pure microspheres. [IMAGES: SEE TEXT]     

Nanosized amorphous calcium carbonate stabilized by poly(ethylene oxide)-b-poly(acrylic acid) block copolymers

Particles of amorphous calcium carbonate (ACC), formed in situ from calcium chloride by the slow release of carbon dioxide by alkaline hydrolysis of dimethyl carbonate in water, are stabilized against coalescence in the presence of very small amounts of double hydrophilic block copolymers (DHBCs) composed of poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) blocks. Under optimized conditions, spherical particles of ACC with diameters less than 100 nm and narrow size distribution are obtained at a concentration of only 3 ppm of PEO-b-PAA as additive. Equivalent triblock or star DHBCs are compared to diblock copolymers. The results are interpreted assuming an interaction of the PAA blocks with the surface of the liquid droplets of the concentrated CaCO3 phase, formed by phase separation from the initially homogeneous reaction mixture. The adsorption layer of the block copolymer protects the liquid precursor of ACC from coalescence and/or coagulation.     

Phase behavior of biodegradable amphiphilic poly(l,l-lactide)-b-poly(ethylene glycol)-b-poly(l,l-lactide)

This study describes the miscibility phase behavior in two series of biodegradable triblock copolymers, poly(l-lactide)-block-poly(ethylene glycol)-block-poly(l-lactide) (PLLA-PEG-PLLA), prepared from two di-hydroxy-terminated PEG prepolymers (M_n = 4000 or 600 g mol⁻¹) with different lengths of poly(l-lactide) segments (polymerization degree, DP = 1.2-145.6). The prepared block copolymers presented wide range of molecular weights (800-25,000 g mol⁻¹) and compositions (16-80 wt.% of PEG). The copolymer multiphases coexistance and interaction were evaluated by DSC and TGA. The copolymers presented a dual stage thermal degradation and decreased thermal stability compared to PEG homopolymers. In addition, DSC analyses allowed the observation of multiphase separation; the melting temperature, T_m, of PLLA and PEG phases depended on the relative segment lengths and the only observed glass transition temperature (T_g) in copolymers indicated miscibility in the amorphous phase.     

聚乙烯基环己烷-聚乙烯-聚乙烯基环己烷三嵌段共聚物溶液的受限结晶研究

嵌段共聚物由于组分间的化学不相容性而发生微相分离,组装成各种有序的纳米结构,如球、圆柱、层及双连续结构等．半晶型嵌段共聚物由于引入了能结晶的组分,使体系中存在两种相互竞争的过程,即微相分离与结晶,所以能形成更为丰富的有序结构．聚乙烯基环己烷-聚乙烯-聚乙烯基环己烷[Poly(Vinylcyclohexane)-b-poly(ethylene)-b-poly(vinylcyclohexane),     

功能化聚乳酸微球改性聚乳酸膜片表面及其细胞相容性

以两亲三嵌段共聚物PEO PPO PEO及其氨基酸、多肽RGD衍生物作为微球制备过程中的表面稳定剂 ,低分子量的聚乳酸作为成核材料 ,采用o w乳液溶剂挥发法制备得到表面含不同氨基酸的聚乳酸微球 ,荧光标记手段证明了氨基酸存在于微球的表面 ;利用溶胀嵌入固定法将微球固定到具有生物惰性聚乳酸膜片表面 ,制备得到了具有良好稳定性的微球改性聚乳酸生物惰性膜片 ;成骨细胞相容性测试表明 ,氨基酸尤其是多肽RGD在生物惰性聚乳酸表面的引入能较大程度地提高聚乳酸生物惰性表面的细胞相容性 ,能较好地诱导细胞行为如细胞粘附、增殖等过程的发生 ,为实现对细胞行为的诱导控制提供了一种新途径 .     

Synthesis and pH-sensitive micellization of doubly hydrophilic poly(acrylic acid)-b-poly(ethylene oxide)-b-poly(acrylic acid) triblock copolymer in aqueous solutions

A doubly hydrophilic triblock copolymer poly(acrylic acid)-b-poly(ethylene glycol)-b-poly(acrylic acid) (PAA-b-PEO-b-PAA) with M _w/M _n = 1.15 was synthesized by atom transfer radical polymerization of t-butyl acrylate (tBA), followed by acidolysis of the PtBA blocks. The pH-sensitive micellization of PAA-b-PEO-b-PAA in acidic solution was investigated by potentiometric titration, fluorescence spectrum, dynamic light scattering and zeta potential. The pK _a was 6.6 and 6.0 in deionized water and in 0.1 mol/L NaCl solution, respectively. The copolymer formed micelles composed of a weakly hydrophobic core of complexed PAA and PEO and a hydrophilic PEO shell in 1 mg/mL solution at pH < 5.5 due to hydrogen bonding. The critical micelle concentration was 0.168 mg/mL at pH 2.0. At pH < 4.5, steady and narrow distributed micelles were formed. Increasing pH to 5.0, unsteady and broad distributed micelles were observed. At pH > 5.5, the micelle was destroyed owing to the ionization of the PAA blocks.     

Effect of PEO‐PPO‐PEO copolymer on the mechanical and thermal properties and morphological behavior of biodegradable poly (L‐lactic acid) (PLLA) and poly (butylene succinate‐co‐L‐lactate) (PBSL) blends

A blend of two biodegradable and semi‐crystalline polymers, poly (L‐lactic acid) (PLLA; 70 wt%) and poly (butylene succinate‐co‐L‐lactate) (PBSL; 30 wt%), was prepared in the presence of various polyethylene oxide‐polypropylene oxide‐polyethylene oxide (PEO‐PPO‐PEO) triblock copolymer contents (0.5, 1, 2 wt%). Mechanical, thermal properties, and Fourier transform infrared (FTIR) analysis of the blends were investigated. It was found that the addition of copolymer to PLLA/PBSL improved the fracture toughness of the blends as shown by mode I fracture energies. It was supported by morphological analysis where the brittle deformation behavior of PLLA changed to ductile deformation with the presence of elongated fibril structure in the blend with copolymer system. The glass transition temperature (T_g), melting temperature (T_m) of PLLA, and PBSL shift‐closed together indicated that some compatibility exists in the blends. In short, PEO‐PPO‐PEO could be used as compatibilizer to improve the toughness and compatibility of the PLLA/PBSL blends. Copyright © 2010 John Wiley & Sons, Ltd.     

Thermal and self-nucleation behavior of molecular complexes formed by p-nitrophenol and the poly(ethylene oxide) end block within an ABC triblock copolymer

We have been able to prepare a molecular complex between the poly(ethylene oxide) block of a poly(ethylene)-b-poly(ethylene-alt-propylene)-b-poly(ethylene oxide) triblock copolymer and p-nitrophenol (PNP). The composition of the copolymer employed was: 24% PE, 57% PEP and 19% PEO in weight percent. The pure copolymer exhibited a non-conventional thermal behavior since the PEO block displayed a fractionated crystallization process during cooling. The PEO block/PNP complex did not show any apparent crystallization during cooling, instead cold crystallization during heating was observed and an approximately 30°C increase in melting point as compared to the neat PEO block within the copolymer. This caused an overlap in the melting regions of the PE block and the PEO block/PNP complex. The self-nucleation of the PE-b-PEP-b-PEO/PNP complex is very different from that of the neat triblock copolymer. An increased capacity for self-nucleation of the PEO block was produced by the complexation with PNP and therefore the three self-nucleation domains were clearly encountered for both the PE block and for the PEO block/PNP complex. Self-nucleation was able to show that the two crystallizable blocks can be self-nucleated and annealed in an independent way, thereby ascertaining the presence of separate crystalline regions in the triblock copolymer. Through the use of PNP, both the crystallinity and the melting point of the PE-b-PEP-b-PEO block copolymer employed here can be substantially increased. Similar results were obtained by complexation of the same ABC triblock copolymer with resorcinol.     

Two-dimensional self-assembly of linear poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the air-water interface

The interfacial properties of amphiphilic linear diblock copolymers based on poly(ethylene oxide) and poly(epsilon-caprolactone) (PEO-b-PCL) were studied at the air-water (A/W) interface by surface pressure measurements (isotherms and hysteresis experiments). The resulting Langmuir monolayers were transferred onto mica substrates and the Langmuir-Blodgett (LB) film morphologies were investigated by atomic force microscopy (AFM). All block copolymers had the same PEO segment (Mn = 2670 g/mol) and different PCL chain lengths (Mn = 1270; 2110; 3110 and 4010 g/mol). Isothermal characterization of the block copolymer samples indicated the presence of three distinct phase transitions around 6.5, 10.5, and 13.5 mN/m. The phase transitions at 6.5 and 13.5 mN/m correspond to the dissolution of the PEO segments in the water subphase and crystallization of the PCL blocks above the interface similarly as for the corresponding homopolymers, respectively. The phase transition at 10.5 mN/m was not observed for the homopolymers alone or for their blends and arises from a brush formation of the PEO segments anchored underneath the adsorbed hydrophobic PCL segments. AFM analysis confirmed the presence of PCL crystals in the LB films with unusual hairlike/needlelike architectures significantly different from those obtained for PCL homopolymers.     

Synthesis and characterization of (AB)n-type poly(l-lactide)-poly(dimethyl siloxane) multiblock copolymer and the effect of its macrodiol composition on urethane formation

An (AB)_n-type multiblock copolymer containing alternating poly(l-lactide) (PLLA) and poly(dimethyl siloxane) (PDMS) segments was synthesized by chain extension of hydroxyltelechelic PLLA-PDMS-PLLA triblock copolymers, which were prepared by the ring-opening polymerization of l-lactide initiated by α,ω-functionalized hydroxyl poly(dimethyl siloxane), using 1,6-hexamethylene diisocyanate as a chain extender. The triblock and the multiblock copolymers were characterized by FT-IR, ¹H NMR and GPC. From the results of thermal analysis, two glass transition temperatures which were measured by DSC showed the occurrence of phase separation phenomena in the triblock and multiblock copolymers because of the difference of solubility parameters between PLLA and PDMS segments. The effect of the chemical composition of the triblock copolymers, including the Mw and the constitutive segment chain length of the macrodiol, on the development of the Mw of the multiblock was discussed based on diffusion effect. Furthermore, the consumption of the isocyanate groups was determined by FT-IR to investigate the dependence of the reaction kinetics of the urethane formation on the chemical composition of the triblock copolymer. The results reveal that the order of the chain extension reaction depended on the Mw of the triblock copolymer: a second order reaction was transformed into a third reaction as the Mw of the triblock copolymer increased from 7000 to 25,000 (g/mol) perhaps because of the inhibition of the formation of an active complex involved in the catalyzed-urethane reaction by the polymer chain aggregation. Finally, the mechanical properties of the multiblock copolymers demonstrated that the introduction of the extremely flexible PDMS segment substantially improved the elongation at breakage, and the tensile strength and the tensile modulus declined due to the intrinsic elasticity of such segments.     

Influence of physical-chemical interactions on the thermal stability and surface properties of poly(vinyl chloride)-b-poly(hydroxypropyl acrylate)-b-poly(vinyl chloride) block copolymers

The synthesis of poly(vinyl chloride) (PVC) homopolymers and poly(vinyl chloride)-b-poly(hydroxypropyl acrylate)-b-poly(vinyl chloride) (PVC-b-PHPA-b-PVC) block copolymers via a single electron - degenerative transfer mediated living radical polymerisation was carried out on a pilot scale in industrial facilities. The thermal stability of the products was assessed conductimetrically. The block copolymers, that contained a low content of PHPA (below 12 wt.%), showed thermal stability that was approximately three times greater than that of conventional PVC. Inverse gas chromatography study of the copolymers surface showed that there was a decrease in the dispersive component and greater Lewis acidity and basicity constants were observed relative to those of PVC. The thermal stabilisation of PVC when in the presence of PHPA is explained by the interactions between its functional groups and the structures formed during the thermal degradation. The thermal stability and the surface properties of PVC-b-PHPA-b-PVC were strongly dependent on the molecular weight of the block copolymer. Lewis acid-base interaction parameters were determined and are interpreted as evidence of the PVC-b-PHPA-b-PVC compatibilising function in PVC-wood flour composites.     

Synthesis and characterization of biodegradable triblock copolymers based on bacterial poly[(R)‐3‐hydroxybutyrate] by atom transfer radical polymerization

Biodegradable poly(tert‐butyl acrylate)–poly[(R)‐3‐hydroxybutyrate]–poly (tert‐butyl acrylate) triblock copolymers based on bacterial poly[(R)‐3‐hydroxybutyrate] (PHB) were synthesized by atom transfer radical polymerization. The chain architectures of the triblock copolymers were confirmed by ¹H NMR and ¹³C NMR spectra. Gel permeation chromatography analysis was used to estimate the molecular weight characteristics and lengths of the PHB and poly(tert‐butyl acrylate) blocks of the copolymers. The thermal properties of the copolymers were studied by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). TGA showed that the triblock copolymers underwent stepwise thermal degradation and had better thermal stability than their respective homopolymers, whereas DSC analyses showed that a microphase‐separation structure was formed only in the triblock copolymers with the longer PHB block. As a similar result, from wide‐angle X‐ray diffraction experimentation, the crystalline phase of PHB could not be seen evidently in the triblock copolymers with the shorter PHB block. The enzymatic hydrolysis of the copolymer films was carried at 37 °C and pH 7.4 in a potassium phosphate buffer with an extracellular PHB depolymerase from Penicillum sp. The biodegradability of the triblock copolymers increased with an increase in the PHB block content. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4857–4869, 2005     

Synthesis of poly(vinyl acetate-methyl methacrylate) copolymer microspheres using suspension polymerization

Poly(vinyl acetate-methyl methacrylate) (VAc-MMA) copolymer microspheres were prepared using suspension polymerization at low temperature initiated with 2,2'-azobis(2,4-dimethyl valeronitrile) (ADMVN). The poly(VAc-MMA) copolymer microspheres can be used over a large area where homopolymers, polyvinyl acetate (PVAc) and methyl methacrylate (PMMA) microspheres are capable of being put to use. The prepared microspheres were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). Obtained copolymer microspheres which have 200 μm average diameter and higher thermal stability than those of homopolymer.     

Design, synthesis, and aqueous aggregation behavior of nonionic single and multiple thermoresponsive polymers

Nonionic water-soluble poly(acrylamide)s and poly(acrylate)s were synthesized by RAFT and ATRP methods. Similar to the synthesized poly(N-isopropylacrylamide) and poly(N-acryloylpyrrolidine), aqueous solutions of statistical acrylate copolymers bearing two different oligo(ethylene oxide) side chains showed a sharp clouding transition upon heating beyond characteristic temperatures. The temperature of the cloud point can be easily fine tuned by the copolymer composition. As for poly(N-isopropylacrylamide) and poly(N-acryloylpyrrolidine), the cloud-point temperatures of these statistical copolymers are rather insensitive to changes in the molar mass or the NaCl content of the solutions. Also, ternary triblock copolymers containing one permanently hydrophilic block and two different thermoresponsive blocks were synthesized, varying the block sequence systematically. Their aggregation in aqueous solution was followed by turbidimetry and dynamic light scattering. Depending on the heating process and the triblock sequence, micellar aggregates of 40 to 600 nm size were found. The thermally induced aggregation behavior depends sensitively on the block sequence but is also subject to major kinetic effects. For certain block sequences, a thermally induced two-step association is observed when heating beyond the first and second cloud points of the thermoresponsive blocks. However, the thermal-transition temperatures of the block polymers can differ from the thermal-transition temperatures of the individual homopolymers. This may be caused by end-group effects but also by mutual interactions of the different blocks in solution, as physical mixtures of the homopolymers exhibit deviations from a purely additive thermal behavior.     

Continuous synthesis of CdSe(x)Te(1-x) nanocrystals: chemical composition gradient and single-step capping

Thermosensitive poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymer, Pluronic F68, containing a hydrophobic unit, oligo-(lactic acid)(oligo-LA) or oligo-caprolactone (oligo-CL), 2-META and RGD as side groups was successfully synthesized and characterized by (1)H NMR, FTIR, and elemental analysis. Their aqueous solution displayed special gel-sol-gel phase transition behavior with increasing temperature from 10 to 70°C, when the polymer concentration was above critical micelle concentration (CMC). The gel-sol phase diagram was investigated using tube inversion method, rheological measurement, and dynamic light scattering. Based on these results, the gelation properties of modified F68 were affected by several factors such as the composition of the substituents, chain length of oligo L-LA or oligo ε-CL, and the concentration of the polymer solutions. The unique phase transition behavior with temperature was observed by modified F68 triblock copolymer, composed of the PPO blocks core and the PEO blocks shell in aqueous solution. This phenomenon was elucidated using (1)H NMR data; the alteration of hydrophobic interaction and chain mobility led to the formation of transparent gel, coexistence of gel-sol, and opaque gel. These hydrogels may be useful in drug delivery and tissue engineering.     

Preparation and characterization of a novel star ABC triblock copolymer of styrene,ethylene oxide,and methacrylic acid

The preparation of a star triblock copolymer based on polystyrene, poly(ethylene oxide), and poly(methacrylic acid) blocks (S-St-EO-MAA) is described. The polymer structure was achieved by the following route: the polystyrene macroanion (PS_m) was formed first by a butyllithium-initiated polymerization of styrene and capping with Michler's ketone; the resulting N,N,N′,N′-tetramethyl-4,4′-diaminodiphenylmethanol (TDDM)-terminated polystyrene was further reacted with metal potassium. The oxo-anion initiated the ring-opening polymerization of ethylene oxide, and the desired ABC triblock copolymer was obtained by precipitation polymerization of methacrylic acid (MAA) initiated with a charge transfer complex (CTC) under UV irradiation using benzene as a solvent. The complex is composed of PS-b-PEO with a TDDM end group (PS-b-PEO_tm) and benzophenone (BP).     

Poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)-g-poly(vinyl pyrrolidone): synthesis and characterization

Pluronic poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers are grafted with poly(vinyl pyrrolidone) by free radical polymerization of vinyl pyrrolidone with simultaneous chain transfer to the Pluronic in dioxane. This modified polymer has both thermal responsiveness and remarkable capacity to interact with a wide variety of hydrophilic and hydrophobic pharmaceutical agents which is very attractive for medical applications. The chemical structure of the graft copolymers was characterized by FTIR and 1H NMR spectroscopy. Polymerization conditions such as initiators, feed ratio, and reaction times are studied to obtain the ideal graft copolymer.     

Synthesis of poly(N,N‐dimethylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N,N‐dimethylacrylamide) and its application for separation of proteins by capillary zone electrophoresis

A series of well‐defined triblock copolymers, poly(N, N‐dimethylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N, N‐dimethylacrylamide) (PDMA‐b‐PEO‐b‐PDMA) synthesized by atom transfer radical polymerization, were used as physical coatings for protein separation. A comparative study of EOF showed that the triblock copolymer presented good capillary coating ability and EOF efficient suppression. The effects of the M_r of PDMA block in PDMA‐b‐PEO‐b‐PDMA triblock copolymer and buffer pH on the separation of basic protein for CE were investigated. Moreover, the influence of the copolymer structure on separation of basic protein was studied by comparing the performance of PDMA‐b‐PEO‐b‐PDMA triblock copolymer with PEO‐b‐PDMA diblock copolymer. Furthermore, the triblock copolymer coating showed higher separation efficiency and better migration time repeatability than fused‐silica capillary when used in protein mixture separation and milk powder samples separation, respectively. The results demonstrated that the triblock copolymer coatings would have a wide application in the field of protein separation.     

Adsorption of poly(ethylene oxide)-b-poly(epsilon-caprolactone) copolymers at the silica-water interface

The adsorption of amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) and poly(ethylene oxide)-b-poly(gamma-methyl-epsilon-caprolactone) copolymers in aqueous solution on silica and glass surfaces has been investigated by flow microcalorimetry, small-angle neutron scattering (SANS), surface forces, and complementary techniques. The studied copolymers consist of a poly(ethylene oxide) (PEO) block of M(n) = 5000 and a hydrophobic polyester block of poly(epsilon-caprolactone) (PCL) or poly(gamma-methyl-epsilon-caprolactone) (PMCL) of M(n) in the 950-2200 range. Compared to homoPEO, the adsorption of the copolymers is significantly increased by the connection of PEO to an aliphatic polyester block. According to calorimetric experiments, the copolymers interact with the surface mainly through the hydrophilic block. At low surface coverage, the PEO block interacts with the surface such that both PEO and PCL chains are exposed to the aqueous solution. At high surface coverage, a dense copolymer layer is observed with the PEO blocks oriented toward the solution. The structure of the copolymer layer has been analyzed by neutron scattering using the contrast matching technique and by tapping mode atomic force microscopy. The experimental observations agree with the coadsorption of micelles and free copolymer chains at the interface.     

Synthesis of triblock and multiblock methacrylate polymers and self‐assembly of stimuli responsive triblock polymers

Multisegmented poly(methacrylate)s were synthesized using one pot reversible addition fragmentation chain transfer polymerization. Initially, a series of triblock copolymers were synthesized with different ratios of trimethylsilyl methacrylate, di(ethylene oxide) methacrylate, and oligo(ethylene oxide) methacrylate, and different total polymer molecular weights. Additionally, a polymer containing seven distinct blocks of methacrylic monomers was synthesized in one pot. For the triblock copolymers, the trimethylsilyl group was subsequently hydrolyzed, and the self‐assembly of the triblock copolymer was studied in water, under different pH and thermal conditions. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2548–2555