Thermal behaviour of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) tri-block copolymers

Thermal behavior of poly(-caprolactone)-poly(ethylene glycol)-poly(-caprolactone) tri-block copolymers with different block lengths is examined. Thermal behavior of specimens crystallized under the isothermal and dynamic condition are characterized by DSC. Also WAXD and SAXS are employed to investigate the structure. Depending on the relative length of each block, tri-block copolymers can be classified into three groups: PCL dominant crystallization; PEG dominant crystallization; and the competing case. When the crystallization of PEG and PCL are competing, the crystallization of each block shows strong dependency on the thermal hystory of crystallization, leading to multiple melting and crystallization peaks. Also, the typical micro-phase separation of block copolymers seems to play an important role, competing with crystallization, especially under the dynamic crystallization condition.     

Microencapsulation of cytarabine using poly(ethylene glycol)–poly(ε-caprolactone) diblock copolymers as surfactant agents

Background: The high water solubility and the low molecular weight of cytarabine (Ara-C) are major obstacles against its particulate formulation as a result of its low affinity to the commonly used hydrophobic polymers. Methods: Biodegradable cytarabine loaded-microparticles (Ara-C MPs) were elaborated using poly(?-caprolactone) (PCL) and monomethoxy polyethylene glycol (mPEG)–PCL diblock copolymer in order to increase the hydrophilicity of the polymeric matrix. For this purpose, a series of mPEG–PCL diblock copolymers with different PCL block lengths were synthesized. Compositions and molecular weights of obtained copolymers were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, size exclusion chromatography, and size exclusion chromatography–multi-angle laser light scattering. Ara-C MPs were prepared by double emulsion-solvent evaporation method. The effects of varying PCL block lengths on microparticle encapsulation efficiency, size, and zeta potential were evaluated. Results: Increasing the PCL block lengths of copolymers substantially increased the Ara-C encapsulation efficiency and the microparticle size but it decreased their zeta potential. Microparticles were spherical in shape, with a smooth surface and composed of homogenously distributed Ara-C-containing aqueous domains in the polymer matrix. The in vitro drug release kinetics of the optimized microparticles showed a hyperbolic profile with an initial burst release. Conclusion: These results showed the important role of the amphiphilic diblock copolymers as stabilizing agent in the encapsulation of Ara-C in PCL microparticles, suggesting their potential use for the microparticulate formulations of other small hydrophilic bioactive molecules.     

Tissue engineering scaffolds of mesoporous magnesium silicate and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) composite

Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) composite scaffolds were fabricated by solvent-casting and particulate leaching method. The results suggested that the incorporation of m-MS into PCL–PEG–PCL could significantly improve the water adsorption of the m-MS/PCL–PEG–PCL composite (m-MPC) scaffolds. The in vitro degradation behavior of m-MPC scaffolds were determined by testing weight loss of the scaffolds after soaking into phosphate buffered saline (PBS), and the result showed that the degradation of m-MPC scaffolds was obviously enhanced by addition of m-MS into PCL–PEG–PCL after soaking for 10 weeks. Proliferation of MG63 cells on m-MPC was significantly higher than MPC scaffolds at 4 and 7 days. ALP activity on the m-MPC was obviously higher than MPC scaffolds at 7 days, revealing that m-MPC could promote cell differentiation. Histological evaluation showed that the introduction of m-MS into PCL–PEG–PCL enhanced the efficiency of new bone formation when the m-MPC scaffolds implanted into bone defect of rabbits. The results suggested that the inorganic/organic composite of m-MS and PCL–PEG–PCL scaffolds exhibited good biocompatibility, degradability and osteogenesis.     

Self-assembled micellar aggregates based monomethoxyl poly(ethylene glycol)-<Emphasis Type="Italic">b</Emphasis>-poly(ε-caprolactone)-<Emphasis Type="Italic">b</Emphasis>-poly(aminoethyl methacrylate) triblock copolymers as efficient gene delivery vectors

Amphiphilic triblock copolymers monomethoxyl poly(ethylene glycol) (mPEG)-b-poly(ε-caprolactone) (PCL)-b-poly(aminoethyl methacrylate)s (PAMAs) (mPECAs) were synthesized as gene delivery vectors. They exhibited lower cytotoxicity and higher transfection efficiency in COS-7 cells in presence of serum compared to 25 kDa bPEI. The influence of mPEG and PCL segments in mPECAs was evaluated by comparing with corresponding diblock copolymers. The studies showed the incorporation of the hydrophobic PCL segment in triblock copolymers affected the binding capability to pDNA and surface charges of complexes due to the formation of micelles increasing the local charges. The presence of mPEG segment in gene vector decreased the surface charges of the complexes and increased the stability of the complexes in serum because of the steric hindrance effect. It was also found that the combination of PEG and PCL segments into one macromolecule might lead to synergistic effect for better transfection efficiency in serum.     

Preparation and characterization of magnetic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) microspheres

In this article, nano-magnetite particles (ferrofluid, Fe₃O₄) were prepared by chemical co-deposition method. A series of biodegradable triblock poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymers were synthesized by ring-opening polymerization method from ε-caprolactone (ε-CL) initiated by poly(ethylene glycol) diol (PEG) using stannous octoate as catalyst. And the magnetic PCEC composite microspheres were prepared by solvent diffusion method. The properties of the ferrofluid, PCEC copolymer, and magnetic PCEC microspheres were studied in detail by SEM, VSM, XRD, Malvern Laser Particle Sizer, ¹H-NMR, GPC, and TG/DTG. Effects of macromolecular weight and concentration of polymer, and the time for ultrasound dispersion on properties of magnetic microspheres were also investigated. The obtained magnetic PCEC microspheres might have great potential application in targeted drug delivery system or cell separation. This work was financially supported by Chinese Key Basic Research Program (2004CB518800 and 2004CB518807), and Sichuan Key Project of Science and Technology (06(05SG022-021-02)). Qian ZY and Wang H did the even work with Gou ML, and are the co-first authors for this paper.     

Biofunctionalized poly(ethylene glycol)-<Emphasis Type="Italic">block</Emphasis>-poly(ε-caprolactone) nanofibers for tissue engineering

Electrospun fibers with contrasting cell adhesion properties provided non-woven substrates with enhanced in vitro acceptance and controllable cell interactions. Poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) block copolymers with varying segment lengths were synthesized in two steps and characterized by NMR and GPC. A cell adhesive peptide sequence, GRGDS, was covalently coupled to the PEG segment of the copolymer in an additional step. The suitability of polymers with molecular weights ranging from 10 to 30 kDa for electrospinning and the influences of molecular weight, solvent, and concentration on the resulting morphologies were investigated. Generally, electrospun fibers were obtained by electrospinning polymers with molecular weight larger than 25 kDa and concentrations of 10 wt%. Methanol/chloroform (25/75, v/v) mixtures proved to be good solvent systems for electrospinning the PEG-b-PCL and resulted in hydrophilic, non-woven fiber meshes (contact angle 30°). The mesh without cell adhesive GRGDS ligands showed no attachment of human dermal fibroblasts after 24 h cell culture demonstrating that the particular combination of the material and electrospinnig conditions yielded protein and cell repellent properties. The GRGDS immobilized mesh showed excellent cellular attachment with fibroblasts viable after 24 h with spread morphology. Electrospun nanofibers based on block copolymers have been produced which are capable of specifically targeting cell receptor binding and are a promising material for tissue engineering and controlling cell material interactions.     

Synthesis, characterization and hydrolytic degradation study of polyetheresteramide copolymers based on ε-caprolactone, 6-aminocaproic acid, and poly(ethylene glycol)

In this paper, a new kind of biodegradable aliphatic polyetheresteramide copolymers (PEEA) based on -caprolactone, 6-aminocaproic acid, and poly(ethylene glycol) (PEG) were synthesized by melt polymerization method. The obtained copolymers were characterized by ¹H-NMR. The thermal properties of PEEA copolymers were studied by DSC and TGA/DTA under nitrogen atmosphere. The water absorption and hydrolytic degradation behavior was also studied in detail. With the increase in PEG content or the decrease in caprolactone content, the water absorption of the copolymers increased accordingly. For the hydrolytic degradation behavior, with the increase in PEG content or caprolactone content, the degradation rate increased then.     

Functionalization of electrospun fibers of poly(ε-caprolactone) with star shaped NCO-poly(ethylene glycol)-<Emphasis Type="Italic">stat</Emphasis>-poly(propylene glycol) for neuronal cell guidance

Microfibers produced with electrospinning have recently been used in tissue engineering. In the development of artificial implants for nerve regeneration they are of particular interest as guidance structures for cell migration and axonal growth. Using electrospinning we produced parallel-orientated biocompatible fibers in the submicron range consisting of poly(ε-caprolactone) (PCL) and star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) (sPEG). Addition of the bioactive peptide sequence glycine-arginine-glycine-aspartate-serine (GRGDS) or the extracellular matrix protein fibronectin to the electrospinning solution resulted in functionalized fibers. Surface characteristics and biological properties of functionalized and non-functionalised fibers were investigated. Polymer solutions and electrospinning process parameters were varied to obtain high quality orientated fibers. A polymer mixture containing high molecular weight PCL, PCL-diol, and sPEG permitted a chemical reaction between hydroxyl groups of the diol and isocyanante groups of the sPEG. Surface analysis demonstrated that sPEG at the fiber surface minimized protein adhesion. In vitro experiments using dorsal root ganglia explants showed that the cell repellent property of pure PCL/sPEG fibers was overcome by functionalization either with GRGDS peptide or fibronectin. In this way cell migration and axonal outgrowth along fibers were significantly increased. Thus, functionalized electrospun PCL/sPEG fibers, while preventing non-specific protein adsorption, are a suitable substrate for biological and medical applications.     

In vitro degradation and drug release from polymer blends based on poly(<Emphasis Type="SmallCaps">dl</Emphasis>-lactide), poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide-glycolide) and poly(ε-caprolactone)

Bioresorbable materials are extensively used for a wide range of biomedical applications. Accurately modifying and evaluating the degradation rate of these materials is critical to their performance and the controlled release of bioactive agents. The aim of this work was to modify the physical properties, degradation rate and drug delivery characteristics of thin films for medical applications by blending poly(dl-lactic acid) (PDLLA), poly(l-lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL). The thin films were prepared using solvent casting and compression moulding and the in vitro degradation study was performed by immersing the films in a phosphate-buffered saline at elevated temperature for a period of 4 weeks. The degradation rate of the materials was analysed by differential scanning calorimetry, tensile testing and weight loss studies. The thermal analysis of the blends indicated that the presence of PLGA or PDLLA in the film resulted in increased degradation of the amorphous regions of PCL. It was observed that the samples consisting of PDLLA with PCL demonstrated the greatest weight loss. The decrease in mechanical properties observed for both sets of polymer blends proved to be similar. The solvent cast technique was selected as the most appropriate for the formation of the polymer/drug matrices, due to the potentially adverse thermal processing effects associated with compression moulding. It was found that modulation of drug release was achievable by altering the ratio of PCL to PDLLA or PLGA in the thin film blends.     

Particle formation and aggregation–collapse behavior of poly(N-isopropylacrylamide) and poly(ethylene glycol) block copolymers in the presence of cross-linking agent

The effect of feed molar ratio of N-isopropylacrylamide (NIPAM) to poly(ethylene oxide) (PEO) on the particle formation of poly(N-isopropylacrylamide) (PNIPAM) and PEO block copolymers (PNIPAM-b-PEO) and their aggregation-collapse behavior have been studied in aqueous solutions. It is found that in the presence of cross-linking agent N,N'-methylenebisacryla-mide (BIS), different morphologies of PNIPAM-b-PEO copolymers can be obtained, including a grafting-like structure, a hemispherical core-shell structure and a well-defined core-shell nanoparticle, as the feed molar amount of NIPAM in the copolymerization is increased. The increase in temperature causes the self-aggregation of grafting-like copolymers and hemispherical particles due to the hydrophobic interaction between locally unshielded PNIPAM blocks prior to the conformational transition of PNIPAM. When the feed molar ratio of NIPAM to PEO exceeds a certain value, a well-defined core-shell nanoparticle can be produced during the copolymerization. At low concentrations, PNIPAM cores of single core-shell nanoparticles can undergo the conformational transition without aggregation. The increase in the concentration of the well-defined core-shell nanoparticles, however, results in a week aggregation at temperatures lower than the theta-temperature of pure PNIPAM due to the association of methyl groups at the periphery of PEO shells.     

Spectral study of interaction between poly(<Emphasis Type="SmallCaps">l</Emphasis>-lysine)–poly(ethylene glycol)–poly(<Emphasis Type="SmallCaps">l</Emphasis>-lysine) and nucleic acids

Polymer-DNA interactions have attracted considerable interests due to their important application in DNA transfection and cellular drug delivery technologies. In this work, a new detection assay for DNA is proposed with a tri-block copolymer poly(l-lysine)–poly(ethylene glycol)–poly(l-lysine) by resonance light scattering technique with the linear ranges from 0.0656 to 6.56 μg ml⁻¹. The detection limit for DNA is 0.42 ng ml⁻¹. Most coexisting substances do not interfere in the detection. UV-spectra and FTIR-spectra were employed to demonstrate the mechanisms of the interaction that the conformation of the DNA changes because the microenvironment of DNA changes.     

Study on the shape memory effects of poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactide-co-ε-caprolactone) biodegradable polymers

The thermal properties, crystalline structure and shape memory effects of poly(l-lactide) (PLLA) and poly(l-lactide-co-ε-caprolactone) (PCLA) copolymers are systematically investigated by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and tensile tests. The effects of the deformation strain on the shape recovery rate and recovery stress are also revealed. The polymers have the PLLA crystal and the amorphous phase, which are served as the fixed phase and reversible phase, respectively. The shape recovery rate and the recovery stress are significantly affected by the compositions and the deformation strain. With the increase of the deformation strain, the shape recovery rate decrease and higher shape recovery rate can be obtained in the polymers which have higher ε-CL content. However, the variation of recovery stress with the deformation strain is quite different and the maximum recovery stress of all polymers exceeds 3 MPa.     

Encapsulation and controlled release of lysozyme from electrospun poly(ε-caprolactone)/poly(ethylene glycol) non-woven membranes by formation of lysozyme–oleate complexes

In this study, the concept of hydrophobic ion pairing was adopted for incorporating lysozyme into electrospun poly(ε-caprolactone) (PCL)/poly(ethylene glycol) (PEG) non-woven membranes. The solubility of lysozyme in organic solvent was enhanced through the formation of lysozyme–oleate complexes, which could be directly loaded into PCL/PEG membranes using electrospinning technique. The resultant PCL/PEG nanofibers have a compact structure with an average diameter ranged from about 0.4 μm to 0.9 μm. The addition of PEG into the PCL nanofibers not only improved the hydrophilicity of the membrane, but also played an important role on in vitro lysozyme release rate. It was found that the release rate of lysozyme was enhanced with the increase of PEG content. In addition, the increase of salt concentration in the release medium accelerated lysozyme release. It has also been shown that the released lysozyme retained most of its enzymatic activity.     

Synthesis and characterization of biodegradable polyurethane based on poly(ε-caprolactone) and L-lysine ethyl ester diisocyanate

A biocompatible diisocyanate, lysine ethyl ester diisocyanate, was prepared. Afterwards, biodegradable polyurethane (PU) was synthesized by the stepgrowth polymerization of this diisocyanate with hydroxyl terminated poly(ε-caprolactone) in the presence of 1,4-butanediol as a chain-extender. The resulting PU was characterized by GPC, IR and DSC measurements. Its mechanical strength was found to increase with increasing the hard segment content. The PU microfiber meshes with high porosity were obtained by solution electrospinning technique. Their degradation behavior in the PBS and enzymatic solution was also investigated.     

Interpenetrating polymer networks (IPN) based on gelatin/poly(ethylene glycol) dimethacrylate/clay nanocomposites: Structure–properties relationship

The effects of cross-linking sequence (simultaneous or sequential) and incorporation of exfoliated sodium-montmorillonite (Na⁺-MMT) nanoclay on the structure and properties of interpenetrating polymer networks (IPNs) based on gelatin/poly(ethylene glycol)dimethacrylate were studied by means of different complementary techniques. Gelatin and PEGdmA phases were cross-linked via chemical and in-situ UV curing, respectively. 2,2-dimethoxy-2-phenylacetophenone (DMPA) (1.5% w/w) was used as photo-initiator to cross-link PEGdmA. The results showed that the incorporation of small amount of Na⁺-MMT nanoplatelets accelerates the kinetics of chemical cross-linking of gelatin by glutaraldehyde (1.0% w/w). This led to a new hypothesis concerning the tuning structural evolution of the IPNs by the Na⁺-MMT content. In the case of simultaneous IPNs, in which both phases cross-linked at the same time, the accelerated cross-linking of gelatin in the presence of exfoliated sodium-montmorillonite led to increased structural homogeneity, improved mechanical and thermal properties. Incorporation of nanoclay did not show any significant effect on the structure and properties of the IPNs synthesized via sequential method in which gelatin and PEGdma phases were cross-linked separately. For the semi-IPNs, however, Na⁺-MMT induced macroscopic phase separation and resulted in lower mechanical properties. These results might shed light on the mechanisms underlying structure–property relationship in biohybrid IPNs based on gelatin as promising candidates for tissue engineering and drug delivery applications.     

Fabrication of hydroxyapatite-poly(<Emphasis Type="Italic">ε</Emphasis>-caprolactone) scaffolds by a combination of the extrusion and bi-axial lamination processes

Hydroxyapatite (HA)/poly(ε-caprolactone) (PCL) composite scaffolds were fabricated using a combination of the extrusion and bi-axial lamination processes. Firstly, HA/PCL composites with various HA contents (0, 50, 60, 70 wt%) were prepared by mixing the HA powders and the molten PCL at 100 °C and then extruded through an orifice with dimensions of 600 × 600 μm to produce HA/PCL composite fibers. Isobutyl methacrylate (IBMA) polymer fiber was also prepared in a similar manner for use as a fugitive material. The 3-D scaffold was then produced by the bi-axial lamination of the HA/PCL and IBMA fibers, followed by solvent leaching to remove the IBMA. It was observed that the HA/PCL composites had a superior elastic modulus and biological properties, as compared to the pure PCL. The fabricated HA/PCL scaffold showed a controlled pore structure (porosity of ∼49% and pore size of ∼512 μm) and excellent welding between the HA/PCL fibers, as well as a high compressive strength of ∼7.8 MPa.     

Negative temperature coefficient thermistor based on BaFe<Subscript><Emphasis Type="Italic">x</Emphasis></Subscript>Sn<Subscript>1−<Emphasis Type="Italic">x</Emphasis></Subscript>O<Subscript>3−ε</Subscript> solid solutions

A negative temperature coefficient (NTC) thermistors based on BaFe _x Sn_1−x O_3−ε were fabricated by conventional solid-state reaction method. The microstructure and electrical properties of the NTC thermistors were characterized by X-ray diffraction (XRD), electric (R(T)), and impedance measurements. The XRD analysis shows that the BaFe _x Sn_1−x O_3−ε still remains cubic perovskite structure and the crystal growth orientation changes at higher Fe content. Similarly, the electric measurements indicates that all the samples show typical NTCR behavior; with increasing Fe content, the room temperature resistivity, activation energy, and thermistor constant decrease, are in the range of 2.52–217 KΩ cm, 0.343–0.43 eV, and 3900–4896 K, respectively. The impedance spectroscopy confirms that the observed ac resistance, consisting of the grain bulks, grain boundaries, and electrode–ceramic interface, mainly attributes to the grain boundaries and grain bulks; with the rise in temperature the grain boundary resistance shows more rapid change than the grain resistance; moreover, the Fe concentration can greatly affect the grain and grain boundary resistance.     

Injectable hydrogels with two different rates of drug release based on pluronic/water system filled with poly(ε-caprolactone) microcapsules

The present paper regards the preparation and characterization of Pluronic F127?+?F68/water/poly (ε-caprolactone) microcapsules (MCs) composite systems for tissue repair. The first part of the work relates to the production of poly(ε-caprolactone) (PCL) MCs via water-in-oil-in-water (W/O/W) double emulsion system combined with solvent evaporation method. The study of different process parameters in the final MCs characteristics and their drug release profile is herein reported. Different percentages of PCL, emulsion stabilizer, and volume proportions of the emulsion constituents have been tested, leading to considerable differences in the MCs size distributions. The selected MCs, containing an aqueous solution of methylene blue (MB) as a model drug, were then used to fill a Pluronic F127?+?F68/water system leading to the final composite system (5 and 10 wt % MB loaded PCL MCs). The composite systems were characterised in the second part of the work in terms of its rheological behaviour and drug release performance. They were found to gellify at 30 °C, and present an extended drug release to a total of 18 days. The models that best define the release profiles were also studied, with the release of MB occurring mostly by Fick diffusion and polymer chain relaxation. Pluronic F127?+?F68/water/poly (ε-caprolactone) MCs composite system is shown to be a promising injectable system, with two different drug release rates, for tissue repair.

     

Emulsion electrospun vascular endothelial growth factor encapsulated poly(<Emphasis Type="SmallCaps">l</Emphasis>-lactic acid-<Emphasis Type="Italic">co</Emphasis>-ε-caprolactone) nanofibers for sustained release in cardiac tissue engineering

Emulsion electrospinning is a novel approach to fabricate core–shell nanofibers, and it is associated with several advantages such as the alleviation of initial burst release of drugs and it protects the bioactivity of incorporated drugs or proteins. Aiming to develop a sustained release scaffold which could be a promising substrate for cardiovascular tissue regeneration, we encapsulated vascular endothelial growth factor (VEGF) with either of the protective agents, dextran or bovine serum albumin (BSA) into the core of poly(l-lactic acid-co-ε-caprolactone) (PLCL) nanofibers by emulsion electrospinning. The morphologies and fiber diameters of the emulsion electrospun scaffolds were determined by scanning electron microscope, and the core–shell structure was evaluated by laser scanning confocal microscope. Uniform nanofibers of PLCL, PLCL–VEGF–BSA, and PLCL–VEGF–DEX with fiber diameters in the range of 572 ± 92, 460 ± 63, and 412 ± 61 nm, respectively were obtained by emulsion spinning. The release profile of VEGF in phosphate-buffered saline for up to 672 h (28 days) was evaluated, and the scaffold functionality was established by performing cell proliferations using human bone marrow derived mesenchymal stem cells. Results of our study demonstrated that the emulsion electrospun VEGF containing core–shell structured PLCL nanofibers offered controlled release of VEGF through the emulsion electrospun core–shell structured nanofibers and could be potential substrates for cardiac tissue regeneration.