Poly(ε-caprolactone)-block-poly(ethyleneoxide) -block-poly(ε-caprolactone): Biodegradable triblock copolymer spread at the air-water interface

Synthesis, characterization and behavior at the air-water interface of A-B-A triblock copolymers are reported. The copolymers consist of a poly(ethylene oxide) central block and poly(ε-caprolactone) lateral blocks. The synthesis was controlled in order to obtain central and lateral blocks of variable length. Copolymer characterization was performed by FTIR and ¹H NMR spectroscopy, size exclusion chromatography (SEC), and thermal analysis. Monolayers of the copolymers at the air-water interface were obtained by the Langmuir technique and the respective isotherms were obtained by monolayer compression. The limiting area per repeat unit (A_o) and the critical exponent of the excluded volume (ν) for spread monolayers were obtained. The static elasticity (ε₀) of the monolayers was also determined. The obtained results allow proposing a schematic model of the orientation of the different blocks during the compression of the respective monolayers.     

Microwave-Assisted Synthesis of Poly(ε-caprolactone)-block-poly(ethylene glycol) and Poly(lactide)-block-poly(ethylene glycol)

Summary: This study reported the preparation and characterization of PCL-b-mPEG (poly(ε-caprolactone)-block-poly(ethylene glycol)) and PLL-b-mPEG (poly(L-lactide)-block-poly(ethylene glycol)) diblock copolymers by microwave heating and comparison of resulted products the ones with prepared by conventional heating. Diblock copolymers were synthesized successfully by the microwave-assisted ROP in the presence of stannous octoate (SnOct₂) as catalyst under nitrogen atmosphere in different monomer ratios. Structural and functional characterization of copolymers were performed by FTIR, ¹H-NMR and DSC. Molecular weight values were determined by GPC and also calculated from ¹H-NMR. According to the results, microwave irradiation allowed to obtain polymers with very narrow size distribution in very short reaction time. Similar polymers prepared by conventional heating were also synthesized for comparison. Molecular weight and conversion of polymers were increased by irradiation time. This change was continued until a certain time point after which no more increase was observed. It was concluded that microwave irradiation is a succesful method to obtain these diblock copolymers in very short reaction time and with a similar conversion obtained by conventional method.     

In situ study of the breakout crystallization in the poly(butadiene)-block-poly(ε-caprolactone) thin film

Despite its wide occurrence in soft confined block co-polymers, breakout crystallization remains poorly understood and is difficult to control. In this work, thin films of cylinder-forming poly(butadiene)-block-poly(ε-caprolactone) (PB-b-PCL) diblock co-polymers, with PCL being the minority block, have been chosen as the study subject. We demonstrate a new route to study the breakout crystallization by obtaining the microphase separation structure within terraced lamellae first and then in situ tracking down the lamellar coalescence, resulting from the development of the crystal growth front. We find that the crystal growth front has sucked materials from the surrounding amorphous lamellae, which lead to the decrease of the lamellar zones and coalescence of the microphase separation structure. Dividing the breakout crystallization into parallel breakout and vertical breakout, we illustrate that it is the crystallization-driven molecular diffusion that make the molecules overcome the topography constraint and grow into large-scale spherulite. Moreover, the results show that the polymer microphase separation structure has a significant influence on the crystal nucleation and greatly retarded the crystal growth rate. With a well-designed microphase separation structure within terraces and an easily tunable atomic force microscopy in situ imaging technique, an intensive study of the breakout crystallization and concomitant microdomain coalescence has been offered.     

Synthesis and characterization of poly(ε-caprolactone)-block-poly[N-(2-hydroxypropyl)methacrylamide] micelles for drug delivery

Amphiphilic block copolymers based on HPMA and ε-CL were synthesized by ring-opening polymerization of ε-CL followed by RAFT polymerization of HPMA. A copolymer composed of 34 kDa PHPMA and 8.5 kDa PCL associated into micelles with CMC of 5.4 μg · mL(-1) . A novel retinoid, 3-Cl-AHPC-OMe, was incorporated into micelles with 25 wt.-% loading by dialysis method. The effective diameter of drug loading micelles was 117 nm. Incubation of micelles in PBS at 37 °C indicated 86 wt.-% of the drug was released after 96 h. Cytotoxicity studies performed with C4-2 prostate cancer cells showed the IC(50) dose was 1.96 μM after 72 h of incubation, whereas the micelles without drug showed no cytotoxicity.     

温敏性Pluronic-b-poly((ε-caprolactone)-co-(6-(benzyl-oxycarbonylmethyl)-ε-caprolactone))的合成和性能研究

以聚乙二醇99-b-聚丙二醇69-b-聚乙二醇99(PEO99-b-PPO69-b-PEO99 Pluronic F127)为大分子引发剂,引发己内酯(CL)和6-乙酸苄酯-己内酯(BCL)开环聚合得到一系列不同BCL含量的两亲性嵌段共聚物Pluronic-b-poly((ε-caprolactone)-co-(6-(benzyl-oxycarbonylmethyl)-ε-caprolactone))(Pluronic-b-P(CL-co-BCL)).通过核磁共振,红外光谱和凝胶渗透色谱确定共聚物的结构、组成和分子量及其分布.热重分析、X射线衍射和差示扫描量热法的结果表明,聚合物的热稳定性及结晶性均可通过调控共聚物中BCL的含量进行调控.通过乳化溶媒挥发法制备聚合物胶束,并用荧光光谱,扫描电镜和粒径分析仪研究聚合物胶束的形成,形态和大小,结果表明胶束呈现规整球形且分布较为均匀,均具有较小的临界胶束浓度且受聚合物中BCL比例的影响;由光散射的结果看出,随着BCL的引入,Pluronic-b-P(CL-co-BCL)胶束粒径呈现出可逆的温度敏感性变化.     

Synthesis, characterization and self-assemble behavior of chitosan-O-poly(ε-caprolactone)

A facile strategy was proposed for synthesizing chitosan-O-poly(ε-caprolactone) (CS-O-PCL). Stoichiometric sodium dodecyl sulfate-chitosan complex (SCC) which was soluble in common organic solvents was adopted as an intermediate. Regioselective conjugation of PCL onto SCC could be achieved through condensation reaction between isocyanate-terminated PCL and hydroxyl groups of chitosan. The grafting level of PCL could be modulated by varying PCL/SCC weight ratio. SDS was removed from SCC-O-PCL using trihydroxymethylamine (Tris) as a decomplexation agent. The self-assemble behavior of the amphiphilic copolymers was studied by fluorometry, TEM and laser light scattering. The morphology of the CS-O-PCL nanoparticles was found to be dependent on PCL grafting level. Both spherical micelles and vesicle could be formed by dialysis method.     

Synthesis and Antibacterial Activity of Selenium-functionalized Poly(ε-caprolactone)

A selenium-functionalizedε-caprolactone was synthesized by introducing a phenyl selenide group at the 7-position.A polymer was obtained through the ring-opening polymerization of this monomer in a base/thiourea binary organocatalytic system.A living polymerization process was achieved under mild conditions.The resulting polymers had a controlled molecular weight with a narrow molecular weight distributions and high end-group fidelity.Random copolymers could be obtained by copolymerizing this monomer withε-caprolactone.The thermal degradation temperature of the obtained copolymers decreased with the increasing molar ratio of selenide functionalized monomer in copolymers,while the glass transition temperature increased.In addition,the phenyl selenide side group could be further modified to a polyselenonium salt,which resulted in a polymer with good antibacterial properties.The survival rate of E.coli and S.aureus was only 9%with a polymer concentration of 62.5μg/mL.     

Melting of poly(ε-caprolactone) studied by step-heating calorimetry

This study demonstrates that the step-heating calorimetry, which is a kind of temperature-modulated differential scanning calorimetry, can provide valuable information on the polymer melting. Time-dependent heat flow due to the melting of lamellar crystallites in a narrow range of thickness can be directly observed, from which thickness distribution of lamellar crystallites and thickness dependence of the melting kinetics are deduced. A sample of poly(ε-caprolactone) was used as a model material of semi-crystalline polymer, which has high crystallinity (0.79) so that no recrystallization and/or reorganization occur during melting in the step-heating scan. It was revealed that superheating dependence of the melting rate coefficient increases with increasing lamellar thickness, which may be attributed to variation of the fold surface roughness with respect to lamellar thickness. Analysis based on the cylindrical nucleation model revealed much lower free energy values of lateral surface than that evaluated from crystallization behavior, suggesting that the nucleus for melting is more stable than that for crystallization.     

Poly(ε-caprolactone) (PCL)/cellulose nano-crystal (CNC) nanocomposites and foams

Poly(ε-caprolactone) (PCL)/cellulose nanocrystal (CNC) nanocomposites were produced via twin-screw extrusion. Microcellular nanocomposite samples were produced with microcellular injection molding using carbon dioxide (CO₂) as physical blowing agent. The foaming behavior, physical properties, thermal properties, crystallization behavior, and biocompatibility were investigated. It was found that the CNCs interacted with the PCL matrix which led to a strong interface. The CNCs effectively acted as nucleation agents in microcellular injection molding. Both solid and foamed samples with higher levels of CNC content showed higher tensile moduli, complex viscosities, and storage moduli due to the reinforcement effects of CNCs. Furthermore, improvement in the foamed samples was more significant due to their fine cell structure. The addition of CNCs caused a reduction of the decomposition temperature and an increase in the glass transition temperature, crystallization temperature, and crystallinity of PCL. Moreover, the biocompatibility of the foamed nanocomposites with low CNC content was verified by 3T3 fibroblast cell culture.     

Anionically prepared poly(ε-caprolactam-co-ε-caprolactone) and poly(ε-caprolactam-co-δ-valerolactone) copolymers: Thermal and mechanical properties

Thermal and representative physico-mechanical properties of newly prepared poly[(ε-caprolactam)-co-(ε-caprolactone)] and poly[(ε-caprolactam)-co-(δ-valerolactone)] copolymers were studied. The copolymers were synthesized by anionic polymerization of ε-caprolactam activated by isocyanate end-capped oligomeric aliphatic polyesters designated as the macroactivators (MAs). Type, concentration and molecular weight of the MAs were varied, which resulted in copolymers with different structure and properties. The impact of the new MAs used in this study on the glass transition temperature and the melting temperature of poly-ε-caprolactam was investigated by DSC. DMTA was used to analyze the effect of copolymerization on the storage modulus (E^′) and tan δ of poly-ε-caprolactam. Conventional and high-resolution TGA data revealed that all the synthesized polyesteramides possess good thermal stability. Mechanical properties were studied by notched impact and tensile testing. According to the experimental data the impact toughness increase with the MA content, being six time higher compared to the poly(ε-caprolactam) in the best situation. Water absorption was also considered in relation to the composition of the copolymers.     

Controlled-release and antibacterial studies of doxycycline-loaded poly(ε-caprolactone) microspheres

The objective of the present study is to achieve doxycycline’s maximum therapeutic efficacy. Doxycycline-loaded poly(ε-caprolactone) microspheres were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation technique with different formulation variables such as concentrations of drug and polymer. The effects of these variables on surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior were examined. To observe the nature of microspheres, X-ray diffraction studies were carried out. The release data obtained were determined using various kinetic models and Korsmeyer–Peppas model showed an acceptable regression value for all compositions. Antibacterial efficiency of doxycycline-loaded poly(ε-caprolactone) microspheres were assessed by determining Minimum Inhibition Concentration (MIC) by standard tube dilution method against four standard pathogenic strains. The in vitro drug release studies were carried out in phosphate buffer solution (pH 7.2). The results showed marked retardation of doxycycline release and higher percentage of polymer gave longer drug release profile. This may definitely provide a useful controlled-release drug therapy and also prove to be effective over a long period of time (76 h).     

Cellular integration and vascularisation promoted by a resorbable, particulate-leached, cross-linked poly(ε-caprolactone) scaffold

Flexible, strong scaffolds were created by crosslinking PCL with 1,6‐hexamethylenediisocyanate, using paraffin beads as a porogen. Particulate leaching generated homogeneous scaffolds with interconnected spherical pores of 5–200 µm. Subcutaneous implantation in rats for 3 months resulted in minimal scaffold resorption and a non‐inflammatory regenerative host response, with complete infiltration by alternatively‐activated CD68⁺ macrophages. In addition, scaffolds were populated extensively along microfractures by a stromal matrix, which was highly vascularised and contained a subset of stromal cells that expressed the anti‐inflammatory CD163 antigen. Such microfractures may be an important physical feature for directing stromal integration and vascularisation events.

     

A facile synthesis of hydrophilic poly(ε-caprolactone)-based poly(ether-ester-amide)s

Segmented poly(ether-ester-amide)s, (PEEA)s, of controlled hydrophilicity degree, based on poly(ε-caprolactone) (PCL), were synthesized according to a facile two-step procedure using α,ω-dihydroxy oligomeric PCL, 4,7,10-trioxa-1,13-tridecanediamine and macromers prepared from poly(ethylene glycol)s and adipoyl chloride. The PEEAs showed M _n values in the range 5–11.5 kDa. A PCL-type crystallinity was found by WAXS. DSC indicated T_m values (49–51 °C) close to that of PCL macromer. Single glass transitions were observed both by DSC and DMTA techniques and the T_g values (−58–−50 °C by DSC) were slightly higher than that of PCL. The water uptake was in the range 4.8–26.0 wt.-% depending on the length of the poly(ethylene glycol) segment.

Monomers used to prepare the PEEAs.     

pH-responsive star-shaped functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) with amino groups

Functional star-shaped 4-arm poly(ethylene glycol)-b-poly[(ε-caprolactone-co-γ-amino-ε-caprolactone)] (4-arm PEG-b-P(CL-co-ACL) was synthesized through ring-opening polymerization. The structure of the copolymer was confirmed by ¹H NMR, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). To further understand the copolymers, the difference of the conversion rate between ε-caprolactone (CL) and γ-(carbamic acid benzyl ester)-ε-caprolactone (CABCL) and the detailed deprotection condition were studied. The thermal property of the copolymer was analyzed by WAXR and differential scanning calorimetry (DSC), which demonstrated that the thermal property could be well adjusted. The pH-responsive behavior of the copolymers was studied in detail by dynamic light scattering (DLS), pH titration, and pyrene fluorescence methods, which indicated that it could form micelles and exhibit pH responsibility. Moreover, the copolymer was nontoxic and had good biocompatibility according to the results by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay.     

Crystallizability of Poly(ε-caprolactone) Blends with Poly(vinylphenol) under Different Conditions

The intermolecular interaction between poly（vinylphenol） （PVPh） and polycaprolactone （PCL） and the crystallization behavior of PCL in PCL/PVPh blends with different compositions and under different conditions were investigated by Fourier transform infrared spectra （FTIR） and differential scanning calorimetry （DSC）. It has been shown that the PCL in the blends with different blend ratios all exists in crystalline state after solution casting, even though the crystallinity decreases with increasing PVPh content. For the melt crystallized samples, PCL in its 80/20 PCL/PVPh sample can still crystallize. The crystallinity is, however, lower than that of the solution cast sample. For blends containing 50% or 20% PCL, the as-cast samples are semicrystalline and can change to compatible amorphous state after heat treatment process. FTIR analysis shows the existence of hydrogen bonding between PCL and PVPh and the fraction of hydrogen bonds increases remarkably after heat treatment process.     

Hydrophobicities of poly(ε-caprolactone) oligomers functionalized with different succinic anhydrides

Different succinic anhydrides were used for modification of hydrophobicities of linear and star-shaped poly (ε-caprolactone) oligomers with different molecular weights. Hydroxyl-terminated poly(ε-caprolactone) oligomers were acid-functionalized either with succinic anhydride (SAH) or with alkenylsuccinic anhydrides (ASAs) containing 8 or 18 carbons in their alkenyl chains. Hydrophobicities of the linear and corresponding star-shaped oligomers were investigated by immersion studies and by water contact angle measurements. In comparison with SAH functionalized oligomers, alkenyl chain containing oligomers showed lower thermal transitions and higher hydrophobicities. In addition, oligomers with 18 carbons alkenyl chain showed considerably higher hydrophobicities than corresponding oligomers with 8 carbon alkenyl chain.     

Development of orientation during electrospinning of fibres of poly(ε-caprolactone)

We explore the influence of a rotating collector on the internal structure of poly(ε-caprolactone) fibres electrospun from a solution in dichloroethane. We find that above a threshold collector speed, the mean fibre diameter reduces as the speed increases and the fibres are further extended. Small-angle and wide-angle X-ray scattering techniques show a preferred orientation of the lamellar crystals normal to the fibre axis which increases with collector speed to a maximum and then reduces. We have separated out the processes of fibre alignment on the collector and the orientation of crystals within the fibres. There are several stages to this behaviour which correspond to the situations (a) where the collector speed is slower than the fibre spinning rate, (b) the fibre is mechanically extended by the rotating collector and (c) where the deformation leads to fibre fracture. The mechanical deformation leads to a development of preferred orientation with extension which is similar to the prediction of the pseudo-affine deformation model and suggests that the deformation takes place during the spinning process after the crystals have formed.