Thermal characterization of biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide)/methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) blend nanoparticles

Biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (MPEG-b-PDLL) and methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-b-PCL) diblock copolymers were synthesized by ring-opening polymerization of DLL and CL monomers in bulk using stannous octoate, and MPEG as the initiating system. Surfactant-free MPEG-b-PDLL/MPEG-b-PCL blend nanoparticles were prepared by the nanoprecipitation method. The influences of block length and blend ratio on morphology, average size, and thermal properties of the blend nanoparticles were determined. The blend nanoparticles were spherical in shape. The average particle sizes slightly decreased as the MPEG-b-PCL blend ratio increased. ¹H-NMR and thermogravimetry revealed the different MPEG-b-PDLL/MPEG-b-PCL blend ratios of the nanoparticles. Differential scanning calorimetry showed that the MPEG-b-PCL crystallinity steadily decreased as the MPEG-b-PDLL blend ratio increased, suggesting miscible blending between the MPEG-b-PDLL and MPEG-b-PCL in the amorphous phase of the nanoparticle matrix.     

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.     

Effect of molecular architecture on micellization, drug loading and releasing of multi-armed poly(ethylene glycol)-b-poly(ε-caprolactone) star polymers

This study investigated the effect of molecular architecture of amphiphilic star polymers on micelle formation and drug loading and releasing. For this, multi-armed star block copolymers having poly(ethylene glycol) as a hydrophilic block and poly(ε-caprolactone) as a hydrophobic block were synthesized by using a divergent synthetic method consisting of a coupling reaction and a ring opening polymerization. The molecular weight and molecular weight distribution of the block copolymers were characterized by ¹H NMR and GPC measurements. Dynamic light scattering and fluorescence spectroscopic analysis were employed to observe micellization, drug loading, and drug release behaviors. We have figured out that the number of arms is a critical factor that changes critical micelle concentration as well as drug loading and releasing behaviors; increase in the number of arms not only led to lowering the critical micelle concentration and drug release rate but also increased the micelle size and drug loading efficiency.     

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.     

Novel electrospun poly(ε-caprolactone)-based bicomponent nanofibers possessing surface enriched in tertiary amino groups

For the first time preparation of electrospun poly(ε-caprolactone) (PCL) based nanofibers possessing surface enriched in tertiary amino groups is shown. For that purpose the pair PCL and poly(ε-caprolactone)-b-poly[(2-dimethylamino)ethyl methacrylate] (PCL-b-PDMAEMA) diblock copolymers was used. PCL-b-PDMAEMA copolymers were synthesized using a combination of ring-opening polymerization and atom transfer radical polymerization (ATRP). Nanofibers with mean diameters ranging from 400 to 800 nm were obtained. Their morphology was evaluated by scanning electron (SEM) and atomic force microscopy (AFM). It was found that the morphology of the fibers depended on the weight ratio between the partners and the length of the PDMAEMA-block in the copolymers. The enrichment of the fiber surface in tertiary amino groups was studied by X-ray photoelectron spectroscopy (XPS). Increasing the copolymer content and the length of the PDMAEMA-block led to increase of the amount of tertiary amino groups on the fiber surface. The AFM analyses of the mechanical properties of the fiber surface showed that increasing the copolymer content led to decrease of the surface stiffness. The increase of the copolymer content led also to decrease of the melting temperature and the crystallinity degree in respect to PCL from the (co)polymer as determined by differential scanning calorimetry.     

Characterization of poly(ethylene glycol)-b-poly(ε-caprolactone) by liquid chromatography under critical conditions: Influence of catalysts and reaction conditions on product composition

Amphiphilic block copolymers were synthesised by ring opening polymerization of ε-caprolactone with polyethylene glycol monomethyl ether (PEG-MME) using different catalysts (boron trifluoride, sodium hydride, and tin octoate) in a one pot procedure. The products obtained were characterized with respect to their molar mass distribution and content of homopolymers using size exclusion chromatography (SEC), Liquid chromatography under critical conditions (LCCC) and MALDI-TOF-MS. The homopolymers of caprolactone could be separated from the block copolymer by LCCC on a reversed phase column in tetrahydrofurane-water mobile phases with evaporative light scattering detection (ELSD). Residual monomer could be determined under the same conditions using density detection, a separation of the copolymer from residual initiator could be achieved on a normal phase column in acetone-water mobile phases.     

Confined lamella formation in crystalline-crystalline poly(ethylene oxide)-b-poly(ɛ-caprolactone) diblock copolymers

The real time and in situ investigation of the crystallization process and structure transitions of asymmetric crystalline-crystalline diblock copolymers from the melt was performed with synchrotron simultaneous SAXS/WAXS. The asymmetric poly(ethylene oxide)-b-poly(ε-caprolactone) diblock copolymers were chosen for the present study. It was shown that the short blocks crystallized later than the long blocks and final lamellar structure was formed in all of the asymmetric diblock copolymers. The final lamellar structure was confirmed by AFM observation. The SAXS data were analyzed with different methods for the early stage of the crystallization. The Guinier plots indicated that there were no isolated domains formed before the formation of lamellae in the asymmetric diblock copolymers during the crystallization process. Debye-Bueche plots implied the formation of correlated domains during crystallization.     

Novel thermogelling poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) aqueous solutions

The aqueous solutions of poly(e-caprolactone-co-lactide)-poly(ethylene glycol)poly(e-caprolactone-co-lactide) undergoing sol-gel transition as the temperature increases from 20 to 50℃were successfully prepared. The thermogelling triblock copolymers were synthesized by subtle tuning of the chemical composition and the hydrophilicity/hydrophobicity balance. The sol-gel transition was studied focusing on structure-property relationship. The amphiphilic copolymer formed micelles in aqueous solutions. It is believed to have potential applications in drug delivery and tissue engineering.     

Porous multicomponent chitosan/poly(ε-caprolactone)-block poly (ethylene glycol)/SiO2 aerogel@polydopamine membrane for Congo red adsorption

A composite adsorbent, chitosan//poly (ε-caprolactone)-block poly (ethylene glycol)/SiO₂ aerogel@polydopamine (CS/PCL-b-PEG/SA@PDA) membrane was prepared for the adsorption of organic dyes. The matrix polymer materials of this novel adsorbent were eco-friendly. SiO₂ aerogel with nanoporous network construction was fixed in the multicomponent polymer fibers through simultaneous electrospinning-electrospray technology followed by modification of polydopamine (PDA). The composite adsorbent had a maximum adsorption capacity of 598.8 mg/g for Congo red (CR) and possessed good reusability performance. This adsorbent showed excellent performance for the selective adsorption of relatively large molecule CR dyes even under high concentration of small molecule methyl orange (MO) dyes or 1 M of salt solution. The adsorption mechanism indicated that the –NH₂ and –OH groups in adsorbent could generate the stronger electrostatic attraction with the –SO₃^- groups in CR. Meanwhile, the sufficient adsorption spaces of the adsorbent were constructed by the porous network structure of SiO₂ aerogel, the accumulation of PDA particles and the porous structure of the multicomponent composite membrane. The work provided a proactive study in designing an adsorbent for the selective adsorption of organic dyes.     

Novel crosslinked thermoresponsive hydrogels with controlled poly(ethylene glycol)—poly(propylene glycol) multiblock copolymer structure

New thermoresponsive crosslinked hydrogels with controlled multiblock copolymer structure were prepared from equimolar amounts of α,ω-diamino poly(propylene glycol)s with molecular weights (MW) 230, 400, and 2,000 g mol^?1 and diepoxy-terminated poly(ethylene glycol)s of approximate MW 1,000; 2,000; and 4,000 g mol^?1. Their thermoresponsive character was investigated on the 10–70 °C interval, while the swelling behavior was tested at 21, 37, and 50 °C. All hydrogels displayed temperature sensitivity, but a volume phase transition was noticed only in the case of poly(propylene glycol) (PPG)₂₀₀₀-containing hydrogels. The volume phase transition temperature (T _VPT ) depended on the MW of the hydrophilic poly(ethylene glycol) (PEG) chains attached to the PPG₂₀₀₀ block, as well as on the added salts. Longer PEG blocks determined a shift of T _VPT towards higher values, while the influence of the salt added was in agreement with the Hofmeister series, except for NaH₂PO₄ which determined the destruction of the hydrogel network. The equilibrium swelling degree depended on the MW of both PEG and PPG blocks, as well as on temperature. The analysis of the swelling process indicated a modification of the gel characteristics with temperature and second-order kinetics for the water penetration into the hydrogel.     

Thermal degradation of star-shaped poly(?-caprolactone)

Thermal degradation of a serials of star-shaped poly(?-caprolactone) (PCL) with well-defined arm numbers and arm length was investigated. The weight loss of star-shaped PCL during heating process showed a two-stage character, and its dependence on molecular weight and multi-armed structure was well discussed. It was found that the thermal stability could be improved not only by increasing molecular weight but also by increasing arm numbers when the molecular weight is in a certain range. Based on the analyses of pyrolytic products by ¹H NMR and TGA-FTIR, two mechanisms of thermal degradation for the random cleavage of ester bonds of PCL chains were proposed. Ester bonds were pyrolyzed into alkene and carboxyl functional groups in mechanism I while they were pyrolyzed into ketene and hydroxyl functional groups in mechanism II. The effects of multi-armed structure of star-shaped PCL on the cleavage of ester bonds of PCL chains were discussed in terms of the limitation of central “core” on mobility of each PCL arm. Combined the results of viscosity analysis with thermal analysis, it could be concluded that both thermal stability and processability of PCL materials can be improved by controlling the multi-armed structures.     

Synthesis and Characterization of Triblock Terpolymers with three Potentially Crystallisable Blocks: Polyethylene-b-poly(ethylene oxide)-b-poly(ε-caprolactone)

A first attempt was made to produce novel ABC triblock terpolymers with three potentially crystallisable blocks: polyethylene (PE), poly(ethylene oxide) (PEO), and poly(ε-caprolactone) (PCL). Polybutadiene-b-poly(ethylene oxide) diblock copolymers were synthesized by living anionic polymerization. Then, a non-catalyzed thermal polymerization of ε-caprolactone from the hydroxyl end group of the PB-b-PEO diblock precursors was performed. Finally, hydrogenation by Wilkinson catalyst produced PE-b-PEO-b-PCL triblock terpolymers. Side reactions were detected that lead to the formation of undesired PCL-b-PEO diblock copolymers, however, these impurities were successfully removed by purification. A range of triblock terpolymers with PCL and PEO minor components were prepared. Topological restrictions on the PEO middle block prevented this block from crystallizing while the complex crystallization behavior of the PE and PCL blocks was documented by DSC and WAXS measurements.     

Synthesis and micellar characterization of thermosensitive amphiphilic poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) block copolymers

Poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) (PCL-b-PVCL) block copolymers were synthesized as new biocompatible, thermosensitive, amphiphilic block polymers by a combination of ring-opening polymerization and reversible addition–fragmentation chain transfer (RAFT) polymerization, and their thermosensitive micellar behavior was examined. The PCL macro-chain-transfer agent was first synthesized by converting the end group of PCL-OH to O-ethyl xanthate, which was subsequently used for the RAFT polymerization of N-vinylcaprolactam. The critical micelle concentration of PCL-b-PVCL (M _n,NMR?=?56,300?g/mol, polydispersity index?=?1.18) was 0.026?mg/mL. The mean diameter of the PCL-b-PVCL micelles determined by transmission electron microscopy was 55?±?25?nm. The PCL-b-PVCL micelles exhibited repetitive aggregation and dispersion during reversible cooling and heating cycles between 20 and 40?°C due to the thermosensitive behavior of the PVCL shell. Overall, the PCL-b-PVCL block copolymers have potential applications in thermosensitive drug delivery applications.     

Biodegradable star-shaped poly(ethylene glycol)-poly(β-amino ester) cationic pH/temperature-sensitive copolymer hydrogels

Biodegradable star-shaped copolymers comprised of four-arm poly(ethylene glycol) (4-arm PEG) and poly(β-amino ester) (PAE) were synthesized by conjugating PAE to 4-arm PEG. The synthesized copolymers were characterized by ¹H and ¹³C NMR and gel permeation chromatography. The PAE showed pH/temperature-sensitive properties in an aqueous solution. The copolymer solutions (30 wt.%) showed a gel-to-sol phase transition as a function of temperature in the pH range 7.2–7.8. The gel window covers the physiological conditions (37 °C and pH 7.4) and can be controlled by varying the PAE block length, copolymer solution concentration and PEG molecular weight. After a subcutaneous injection of the copolymer solution into a SD rat, a gel formed rapidly in situ which remained for more than 2 weeks in the body. This copolymer is expected to be a potential candidate for biomedical applications.     

Binary blends based on poly(vinyl chloride) and multi-block copolymers containing poly(ϵ-caprolactone) and poly(ethylene glycol) segments

Binary blends based on poly(vinyl chloride) (PVC) were prepared both by casting from tetrahydrofuran (THF) and by mixing in the melt form, in a discontinuous mixer, PVC and multi-block copolymers containing poly(ϵ-caprolactone) (PCDT) and poly(ethylene glycol) (PEG) segments. PCDT-PEG copolymers were synthesized using a polycondensation reaction where the α,ω-bis-chloroformate of an oligomeric poly(ϵ-caprolactone) diol terminated (PCDT) and oligomeric PEG were employed as macromonomers. For comparison purposes, blends PVC with starting oligomers as well as with mixtures containing a typical low molecular plasticizer, dioctylphthalate (DOP), were also prepared. The copolymer miscibility was studied by differential scanning calorimetry (DSC) and FT-IR spectroscopy. The blend morphology was investigated by polarized light microscopy (PLM). A higher miscibility with PVC was observed for copolymers compared to PEG.     

Controlling the properties of poly(amino ester urethane)–poly(ethylene glycol)–poly(amino ester urethane) triblock copolymer pH/temperature-sensitive hydrogel

A series of triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) was synthesized and characterized. Its aqueous solution can be used as a non-cytotoxic, biodegradable, and pH/temperature-sensitive hydrogel system. The copolymer solutions exhibited sol-to-gel and gel-to-sol transitions with increasing pH and temperature, respectively. The properties of this hydrogel system, such as its sol–gel transition diagram, mechanical properties, and degradation rate, can be controlled by modulating the PEG molecular weight, PAEU block length, copolymer concentration, or structure of the monomers. The presence of urethane groups and ionized tertiary amine groups in the copolymer solution at lightly acidic pH may lead to a strong interaction of the copolymer with formulated bioactive therapeutic agents, while the existence of the gel state under physiological conditions (37 °C, pH 7.4) may enable this copolymer hydrogel to be applicable as a drug/protein carrier.     

Solubility of naphthalene in aqueous solutions of poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) triblock copolymers and (2-hydroxypropyl)cyclodextrins

The solubility of naphthalene was investigated in aqueous solutions of triblock copolymers poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) (PEG–PPG–PEG) and (2-hydroxypropyl)cyclodextrins. The results with solutions of the individual solubilizers were as expected: the solubility enhancement was much higher with a micelle-forming copolymer than with the non-micellizing one and with (2-hydroxypropyl)--cyclodextrin (HPBCD) than with (2-hydroxypropyl)--cyclodextrin (HPACD). Although the formation of inclusion complexes between HPACD and PEG and between HPBCD and PPG is well established, the naphthalene solubility in mixed solutions does not significantly deviate from that predicted for a mixture of independent solubilizers. Thus the interactions between HPCD and PEG–PPG–PEG copolymers are not strong enough to disrupt micelles and aggregates formed by those copolymers. In fact, slight synergetic deviations were observed with the micellizing copolymer, indicating the existence of ternary naphthalene/HPCD/copolymer interactions. For pharmaceutical applications, it is important that the solubilization efficacy of PEG–PPG–PEG copolymers and that of cyclodextrins modified by the 2-hydroxypropyl group would not be compromised if these two types of solubilizers were co-administered.     

The behavior of poly(ε -caprolactone) and poly(ethylene oxide)-b-poly(ε -caprolactone) grafted to a poly(glycerol adipate) backbone at the air/water interface

The behavior of crystallizable poly(ε-caprolactone) (PCL) and poly(ε-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) is studied at the air/water interface prior and after grafting to an amorphous poly(glycerol adipate) (PGA) backbone (PGA-g-PCL, PGA-g-(PCL-b-PEO)). Langmuir isotherms are measured and the structure formation in the monolayers on the water surface is followed by Brewster angle microscopy (BAM) and in Langmuir–Blodgett films after a transfer to silicon substrates by atomic force microscopy (AFM). It is observed that PGA-g-PCL forms significantly smaller crystals on the water surface and has smaller crystallization rate compared to PCL homopolymers of identical molar masses as the grafted chains. In contrast to crystals formed by linear PCL, the crystals formed by grafted PCL in PGA-g-PCL do not melt (readsorb at the water surface) in an expansion cycle on the Langmuir trough. Additionally, increasing the subphase temperature at constant surface area significantly above the melting point of linear PCL in bulk results in the formation of a mesophase, and it does lead to the disappearance of crystals. The isotherms of PGA-g-(PCL-b-PEO) show a transition at the surface pressure of ～10 mN/m. This is related to the fact that PEO chains leave the water surface and submerge into the subphase and/or the crystallization of PCL chains. The monolayer collapse appears in an extended plateau region starting at π values of ～30 mN/m. AFM images of Langmuir–Blodgett films reveal that PCL chains in PGA-g-PCL and PGA-g-(PCL-b-PEO) form lamellar crystals with a disk-shape and interconnected platelets, respectively.     

Hydrolytic and microbial degradation of multi-block polyurethanes based on poly(?-caprolactone)/poly(ethylene glycol) segments

Biodegradable amphiphilic multi-block poly(ether-ester-urethane)s were prepared by one-step bulk polycondensation of PEG and PCL macro-diols and HMDI. For biomedical or environmental applications of the proposed materials, one of the critical steps is the study of the degradation characteristics under physiological or environmental conditions. Different ratios of PEG/PCL and molecular weights of the resultant copolymers allowed for tuning their hydrophilicity, as evaluated by water uptake measurements. The swelling results were further supported by microgravimetric measurements performed by QCM-D. In vitro hydrolytic biodegradation was carried out under different conditions (i.e., in phosphate buffer solution - with and without Lipase). Total mineralization in the presence of microorganisms from a sample of river water was observed to follow different kinetics, depending upon the composition and the molecular weight of the copolymer.     

Synthesis of carbon nanofibers from poly(ethylene glycol) with controlled structure

Through fine tuning of synthesis conditions, we successfully synthesized three types of carbon nanofiber (CNF) (herring-bone carbon nanofiber, platelet carbon nanofiber, and cup-stacked carbon nanofiber) by the thermal decomposition of a mixture of poly(ethylene glycol) (PEG) and nickel chloride (NiCl₂). A series of experimental results demonstrated that the key factors for the selective synthesis of these CNFs were the (1) NiCl₂/PEG ratio, (2) drying time of the polymeric mixture, (3) state of PEG (liquid or solid) before temperature rising, and (4) temperature profile during the thermal decomposition. Changes in these conditions contributed to the formation of Ni catalyst particles from the catalyst NiCl₂ with different morphology, thereby resulting in the growth of different types of CNF or amorphous carbon products according to the catalyst particle’s shape. Also, we found that the mechanism of CNF growth in this synthesis method was fundamentally the same as that in chemical vapor deposition (CVD).