Preparation of Electrospun Electroactive Nanofibers of Four Arm Star-Shaped Poly(ε-Caprolactone)-b-Poly(2-Hydroxyethyl Methacrylate) and Its Blends with Polyaniline

A combination of ring-opening polymerization and atom-transfer radical polymerization was used to synthesize a four-arm star-shaped poly(ε-caprolactone)-b-poly(2-hydroxyethyl methacrylate). The structure of obtained copolymer was determined by Fourier transform infrared, ¹H and ¹³C NMR spectroscopies. The uniform electroactive nanofibers consisting blend of four-arm star-shaped poly(ε-caprolactone)-b-poly(2-hydroxyethyl methacrylate) copolymer and polyaniline were produced using electrospinning technique. The electroactivity of prepared nanofibers was investigated using cyclic voltammetry measurement. The morphologies of electrospun nanofibers produced from four-arm star-shaped poly(ε-caprolactone)-b-poly(2-hydroxyethyl methacrylate) and their blends with polyaniline were investigated by the scanning electron microscopy. The presence of polyaniline resulted in significant decrease of sticking fibers.     

Synthesis and characterization of four- and six-arm star-shaped poly(ε-caprolactone)-b-poly(N-vinylcaprolactam): Micellar and core degradation studies

Star-shaped copolymers with four and six poly(ε-caprolactone)-block-poly(N-vinylcaprolactam) (S(PCL-b-PNVCL)) arms were successfully synthesized by combining ring opening polymerization (ROP) of ε-caprolactone (CL) and reversible addition-fragmentation chain transfer (RAFT) polymerization of N-vinylcaprolactam (NVCL). The resulting star copolymers were characterized using ¹H NMR, GPC and UV–vis. The numbers of arms in the star-shaped PCL-b-PNVCL block copolymers were demonstrated using degradation studies under acidic conditions, and the individual PNVCL chains were characterized by GPC and ¹H NMR. In aqueous solution, star-shaped PCL-b-PNVCL block copolymers self-assembled into large aggregates or micelles with sizes varying from 54 to 300 nm, depending on the molecular weight of the copolymer and the relative lengths of the hydrophobic and hydrophilic segments. Micelles were characterized by atomic force microscopy (AFM), dynamic light scattering (DLS) and scanning electron microscopy (SEM).     

One-pot synthesis of poly(N-vinylcaprolactam)-based biocompatible block copolymers using a dual initiator for ROP and RAFT polymerization

Thermosensitive, biocompatible poly(ε-caprolactone)-b-poly(N-vinylcaprolactam) (PCL-b-PVCL), poly(δ-valerolactone)-b-PVCL, and poly(trimethylene carbonate)-b-PVCL block copolymers were synthesized at 30 °C using a hydroxyl-functionalized xanthate reversible addition-fragmentation chain transfer (RAFT) agent, 2-hydroxyethyl 2-(ethoxycarbonothioylthio)propanoate (HECP), as a dual initiator for ring-opening polymerization (ROP) and RAFT polymerization in a one-pot procedure. The hydrophobic blocks were first synthesized by the ROP of cyclic monomers using diphenyl phosphate (DPP) as a catalyst and the RAFT polymerization of the PVCL block was followed by adding N-vinylcaprolactam (VCL) and 2,2′-azobis(4-methoxy-2,4-dimethyl valeronitrile) (V-70) as an initiator to the reaction mixture. This novel one-pot process is convenient and powerful method for the synthesis of the PVCL-based biocompatible block copolymers. The lower critical solution temperature (LCST) of the PVCL-based biocompatible block copolymer can be readily tuned by controlling the hydrophobicity of the block copolymers. By copolymerizing a hydrophilic N-vinylpyrrolidone moiety to the PVCL blocks by RAFT copolymerization, the LCST of the copolymer was matched with the body temperature for its future biomedical applications.     

Dual-sensitive and folate-conjugated mixed polymeric micelles for controlled and targeted drug delivery

For this study, we prepared a new type of drug carrier with the characteristics of stimuli-responsive transition and tumor-specific recognition through the co-assembly of two series of amphiphilic block copolymers, poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-methacryloyl caproic acid] and poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-(2-(methacrylamido)ethyl) folatic amide]. The pH-dependent thermal transition and the content of the targeting ligands of the mixed polymeric micelles are well correlated with the chemical structures and compositions of these two copolymers. Doxorubicin-loaded mixed polymeric micelles are stable at body temperature in the neutral condition for prolonged circulation in blood vessels, and demonstrated rapid drug release at acidic pH levels. The cumulative drug release profiles showed a relatively slow release at pH 7.4, and a quick release of 85% in 3 h at pH 5.3. The cytotoxicity tests against FA-positive (HeLa) and FA-negative (HT-29) tumor cell lines suggest that this mixed polymeric micelle system has potential merits as a controlled and targeted drug delivery system.     

Formation of nanostructures in thermosets containing block copolymers: From self-assembly to reaction-induced microphase separation mechanism

In this work, we investigated the effect of formation mechanisms of nanophases on the morphologies and thermomechanical properties of the nanostructured thermosets containing block copolymers. Toward this end, the nanostructured thermosets involving epoxy and block copolymers were prepared via self-assembly and reaction-induced microphase separation approaches, respectively. Two structurally similar triblock copolymers, poly(ε-caprolactone)-block-poly(butadiene-co-styrene)-block-poly(ε-caprolactone) (PCL-b-PBS-b-PCL) and poly(ε-caprolactone)-block-poly(ethylene-co-ethylethylene-co-styrene)-block-poly(ε-caprolactone) (PCL-b-PEEES-b-PCL) were synthesized via the ring-opening polymerization of ε-caprolactone (CL) with α,ω-dihydroxyl-terminated poly(butadiene-co-styrene) (HO-PBS-OH) and α,ω-dihydroxyl-terminated poly(ethylene-co-ethylethylene-co-styrene) (i.e., HO-PEEES-OH) as the macromolecular initiators, respectively; the latter was obtained via the hydrogenation reduction of the former. Both the triblock copolymers had the same architecture, the identical composition and close molecular weights. In spite of the structural resemblance of both the triblock copolymers, the formation mechanisms of the nanophases in the thermosets were quite different. It was found that the formation of nanophases in the thermosets containing PCL-b-PBS-b-PCL followed a reaction-induced microphase separation mechanism whereas that in the thermosets containing PCL-b-PEEES-b-PCL was in a self-assembly manner. The different formation mechanisms of nanophases resulted in the quite different morphologies, glass transition temperatures (T_g's) and fracture toughness of the nanostructured thermosets.     

Synthesis of pH-Responsive Multilayer Micelles for Sustained Release of Folic Acid

Two novel triblock copolymers poly(hydroxypropyl acrylate)-b-poly (methyl methacrylate)-b-poly(N,N-dimethylaminoethyl methacrylate) and poly(hydroxypropyl acrylate)-b-poly(methyl methacrylate)-b-poly(acrylic acid) were successfully synthesized. In acetone media, using the electrostatic interactions between N,N-dimethylaminoethyl methacrylate and acrylic acid units, they could form spherically shaped multilayer micelles with pH-responsive, and have a mean diameter around 110 nm. The critical micelle concentration of it was determined to be 2.42 mg/L. In vitro release experiments, the folic acid-loaded micelles exhibited sustained release behavior and the drug release rate was affected by the pH value of release media. These results indicate that the multilayer micelles may serve as a novel intelligent drug delivery system.     

One-pot synthesis of poly(vinyl alcohol)-based biocompatible block copolymers using a dual initiator for ROP and RAFT polymerization

Biocompatible poly(ε-caprolactone)-b-poly(vinyl alcohol) (PCL-b-PVA), poly(δ-valerolactone)-b-PVA, and poly(trimethylene carbonate)-b-PVA block copolymers were synthesized at 30 °C using a hydroxyl-functionalized xanthate reversible addition-fragmentation chain transfer (RAFT) agent, 2-hydroxyethyl 2-(ethoxycarbonothioylthio)propanoate, as a dual initiator for ring-opening polymerization (ROP) and RAFT polymerization in a one-pot procedure. The ROP of ε-caprolactone, δ-valerolactone, and trimethylene carbonate was first performed using diphenyl phosphate as the ROP catalyst followed by the RAFT polymerization of vinyl chloroacetate after quenching the ROP with 4-dimethyamino pyridine. The resulting block copolymers were aminolyzed directly to the PVA-based biocompatible block copolymers by adding hexylamine to the reaction mixture. To the best of our knowledge, this is the most convenient method for synthesizing PVA-based biocompatible block copolymers.     

Thermosensitive poly(N-isopropylacrylamide)-b-poly(ε-caprolactone) nanoparticles for efficient drug delivery system

To investigate thermosensitive polymeric nanoparticle, amphiphilic block copolymers of poly(N-isopropylacrylamice)-b-poly(ε-caprolactone) (PNPCL) with different PCL block lengths were synthesized by hydroxy-terminated poly(N-isopropyoacrylamide) (PNiPAAm) initiated ring opening polymerization of ε-caprolactone. Owing to their amphiphilic characteristics, the block copolymers formed self-assembled polymeric nanoparticles in aqueous milieus with thermosensitive PNiPAAm shell compartment. The characterizations of the nanoparticles revealed that the PNPCL nanoparticles showed PCL block length dependent physicochemical characters such as particle sizes, critical aggregation concentrations, and core hydrophobicities. Moreover, the thermosensitive PNiPAAm shells conferred unique temperature responsive properties such as phase transitions with temperature elevation over its lower critical solution temperature (LCST). The temperature induced phase transition resulted in the formation of PNiPAAm hydrogel layer on the PNPCL nanoparticle surface. The drug release tests revealed that the formation of thermosensitive hydrogel layer resulted in the enhanced sustained drug release patterns by acting as an additional diffusion barriers. Therefore, the introduction of thermosensitive polymers on polymeric nanoparticles might be a potential approaches to modulate drug release behaviors.     

Preparation of curcumin loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells

The purpose of this work was to develop implantable curcumin-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanofibers, which might have potential application in cancer therapy. Curcumin was incorporated into biodegradable PCEC nanofibers by electrospinning method. The surface morphology of the composite nanofibers was characterized on Scanning Electron Microscope (SEM). The average diameter of the nanofibers was 2.3-4.5μm. In vitro release behavior of curcumin from the fiber mats was also studied in detail. The in vitro cytotoxicity assay showed that the PCEC fibers themselves did not affect the growth of rat Glioma 9L cells. Antitumor activity of the curcumin-loaded fibers against the cells was kept over the whole experiment process, while the antitumor activity of pure curcumin disappeared within 48 h. These results strongly suggested that the curcumin/PCEC composite nanofibers might have potential application for postoperative chemotherapy of brain cancers.     

Synthesis and self-assembly of a new amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) block copolymer

New amphiphilic thermosensitive poly(N-vinylcaprolactam)/poly(ε-caprolactone) (PNVCL-b-PCL) block copolymers were synthesized by ring-opening polymerization of ε-caprolactone with hydroxy-terminated poly(N-vinylcaprolactam) (PNVCL-OH) as a macroinitiator. The structures of the polymers were confirmed by IR, ¹H NMR and GPC. The critical micelle concentrations of copolymer in aqueous solution measured by the fluorescence probe technique reduced with the increasing of the proportion of hydrophobic parts, so did the diameter and distribution of the micelles determined by dynamic light scattering. The shape observed by transmission electron microscopy (TEM) demonstrated that the micelles are spherical. On the other hand, the UV–vis measurement showed that polymers exhibit a reproducible temperature-responsive behavior with a lower critical solution temperature (LCST). The LCST of PNVCL-OH can be adjusted by controlling the molecular weights, and that of copolymers can be adjusted by controlling the compositions and the concentration. Variable temperature TEM measurements demonstrated that LCST transition was the result of transition of individual micelles to larger aggregates.     

Hydrolysis of poly(ester-ether-ester) block copolymers in the presence of endothelial cells: in vitro modulation of endothelin release

In previous papers, we studied the hydrolytic degradation of six poly(ester-ether-ester) block copolymers, i.e. three poly(ε-caprolactone)-block-poly(oxyethylene)-block-poly(ε-caprolactone) copolymers and three poly(l-lactide)-block-poly(oxyethylene)-block-poly(l-lactide) copolymers. Their degradation products, 6-hydroxyhexanoic acid and l-lactic acid, have now been found to modulate endothelin release by human umbilical vein endothelial cells, with no significant alteration of the vasoconstrictor-vasodilator balance previously determined. The influence of the same degradation products on the cell proliferation has also been determined and discussed. Received: 13 January 1997/Revised: 2 May 1997/Accepted: 3 May 1997     

Synthesis and self-assembly of pH-responsive amphiphilic poly(<Emphasis Type="Italic">ε</Emphasis>-caprolactone)-<Emphasis Type="Italic">block</Emphasis>-poly(acrylic acid) copolymer

The pH-responsive amphiphilic poly(ε-caprolactone)-block-poly(acrylic acid) (PCL-b-PAA) copolymer was prepared by selective hydrolysis of one novel poly(ε-caprolactone)-block-poly(methoxymethyl acrylate) (PCL-b-PMOMA) block copolymer, which was synthesized by combining ring-opening polymerization (ROP) of ε-caprolactone (ε-CL) and atom transfer radical polymerization (ATRP) of methoxymethyl acrylate (MOMA). Selective hydrolysis of the hemiketal ester groups on the PMOMA block gave 100% deprotection without the cleavage of the PCL block. The self-assembly behavior of PCL-b-PAA was investigated by fluorescence spectroscopy, DLS and TEM. The spherical micelles were formed with the hydrophobic PCL block as the core and the hydrophilic PAA as the shell by a co-solvent evaporation method. Moreover, the size and size distribution of the micelles varied with pH value and ionic strength in aqueous solution. The cytotoxicity of the PCL-b-PAA was lower, which was confirmed by MTT assay.     

Synthesis of ε-caprolactone-b-l-lactide block copolymers by mean sequential polymerization,using diphenylzinc as initiator

Block copolymers of ε-caprolactone (CL) and l-lactide (l-LA) were synthesized by sequential polymerization using diphenylzinc as initiator. The composition of the copolymers was adjusted changing the comonomers in ratio. Copolymers were characterized by ¹H-NMR, ¹³C-NMR, DSC, and GPC. Results indicate that poly(ε-caprolactone)-b-poly(l-lactide) (PCL-b-PLA) block copolymers had a narrow molecular weight distribution and well-controlled sequences without random placement.     

Functional Copolymer/Organo-MMT Nanoarchitectures: XXVI. Fabrication and Characterization of Electrospun Nanofibers from PCL/ODA-MMT and Copolymer-g-PLA/ Ag-MMT Blends

We synthesized poly(?-caprolactone)/octadecyl amine-montmorillonite clay nanocomposite as a matrix polymer by solution intercalative method and new amphiphilic poly(maleic anhydrde-alt-1-octadecene)-g-poly(L-lactic acid)/Ag⁺-montmorillonite clay nanocomposite as a partner polymer by interlamellar graft copolymerization of lactic acid onto anhydride copolymer in the presence of silver salt of montmorillonite clay as catalyst-nanofiller. Novel polymer nanofibers were fabricated by electrospinning of matrix/partner blends with different volume ratios. The nanocomposites and nanofibers were investigated by Fourier transform infrared spectroscopy, thermal gravimetric analysis–differential scanning calorimetry, and scanning electron microscope–transmission electron microscope methods. The diameters, morphologies, and thermal behavior of fibers were strongly depended on the partner-polymer nanocomposites loadings. The fabricated biocompatible and biodegradable nanofibers can be utilized for biomedical and filtration applications.     

Electrospinning of polymer melts: Phenomenological observations

Melt electrospinning is an alternative to solution electrospinning, however, melt electrospinning has typically resulted in fibers with diameters of tens of microns. In this paper we demonstrate that polypropylene fibers can be reduced from 35 ± 8 μm in diameter, to 840 ± 190 nm with a viscosity-reducing additive. Melt electrospun blends of poly(ethylene glycol)-block-poly(?-caprolactone) (PEG₄₇-b-PCL₉₅) and poly(?-caprolactone) (PCL) produced fibers with micron-scale diameters (2.0 ± 0.3 μm); this was lowered to 270 ± 100 nm by using the gap method of alignment for collection. The collected melt electrospun fibers often fused together where they touched, allowing the stabilization of relatively thick non-woven felts. The melt electrospun collection also included coiled circles and looped patterns of fibers approximately 150-250 μm in diameter. The polymer jet was visible between the collector and spinneret for particularly significant lengths, and underwent coiling and buckling instabilities close to the collector. The focused deposition of melt electrospun fibers was maintained when multiple jets were observed, with the collections from multiple jets separated by 3.8 ± 0.5 mm for a 5 cm collector gap. The frequent fusion points between melt electrospun fibers, and a reduction in diameter for the gap method of alignment, indicated that the melt electrospun fibers are still slightly molten at collection.     

Biodegradable polyester blends for biomedical application

A new family of bioabsorbable materials suitable for biomedical applications was designed and prepared by means of blending of some available polyesters to develop new biodegradable materials tailored for different requirements. Multiphase polymer blends containing poly(d, l-lactide) (PLA), poly(ε-caprolactone) (PCL), poly(d, l)-lactide-co-poly(ethylene glycol) (PELA), poly(ε-caprolactone) -co-poly(ethylene glycol) (PECL), and poly(ß-hydroxybutyrate) (PHB), PLA/PCL, PELA/PECL, PHB/PLA, PHB/PELA, PHB/PCL, and PHB/PECL blends were respectively investigated. It was found that PLA/PCL, PHB, and PHB/PLA and PHB/PCL blends were seemingly immiscible, with their morphology and hydrolytic behavior were determined by the composition of the blends. On the other hand, the miscibility of PELA/PECL, PHB/PELA, and PHB/PECL blends was improved by using PELA and/or PECL block copolymers that contained poly(ethylene glycol) (PEG) as compatibilizer. The blends showed to a certain extent miscibility, fine phase morphology, and fast hydrolysis. © 1995 John Wiley & Sons, Inc.     

Syntheses of well-defined poly(siloxane)-b-poly(styrene) and poly(norbornene)-b-poly(styrene) block copolymers using functional alkoxyamines

Functional alkoxyamines, 1-[4-(4-lithiobutoxy)phenyl]-1-(2,2,6,6-tetramethylpiperidinyl-N-oxyl)ethane (2) and 1-[4-(2-vinyloxyethoxy)phenyl]-1-(2,2,6,6-tetramethylpiperidinyl-N-oxyl)ethane (3) were prepared, and well-defined poly(hexamethylcyclotrisiloxane)-b-poly(styrene)[poly(D₃)-b-poly(St)] and poly(norbornene)-b-poly(St) [poly(NBE)-b-poly(St)] were prepared using the alkoxyamines. The first step was preparation of poly(D₃) and poly(NBE) macroinitiators, which were obtained by the ring-opening anionic polymerization of D₃ using 2 as an initiator and the ring-opening metathesis polymerization of NBE using 3 as a chain transfer. The radical polymerization of St by the poly(D₃) and poly(NBE) macroinitiators proceeded in the ‘living’ fashion to give well-defined poly(D₃)-b-poly(St) and poly(NBE)-b-poly(St) block copolymers.     

Synthesis, characterization, and drug delivery research of an amphiphilic biodegradable star-shaped block copolymer

An amphiphilic biodegradable three-arm star-shaped diblock copolymer containing poly(ε-caprolactone) (PCL) and poly(N-vinylpyrrolidone) (PVP) (TEA(PCL-b-PVP)₃) has been successfully synthesized by the ring-opening polymerization of ε-caprolactone (ε-CL), RAFT polymerization of N-vinylpyrrolidone and a coupling reaction of PCL with carboxyl-terminated PVP (PVP-COOH). In aqueous media, the star-shaped copolymer self-assembled into spherical micelles with diameters of near 106 nm. The critical micelle concentration of TEA(PCL-b-PVP)₃ copolymer was determined to be 5.96 × 10^?3 mg/mL. Folic acid was then used as a model drug to incorporate into TEA(PCL-b-PVP)₃ micelles, the drug loading content and encapsulation efficiency is 16.36 and 49.08 %, respectively. In vitro release experiments of the drug-loaded micelles exhibited sustained release behavior and it was affected by the pH of release media. These results indicate that the copolymer may serve as a promising “intelligent” drug delivery alternative.     

The Effect Acetic Acid has on Poly(N-Vinylcaprolactam) LCST for Biomedical Applications

The aim of this research was to synthesize Poly(N-vinylcaprolactam) (PNVCL) with the incorporation of hydrophilic acetic acid with thermosensitive N–vinylcaprolactam for potential drug delivery applications. Preparation of the heterogeneous mixture involved photopolymerization of a combination of N–vinylcaprolactam and acetic acid at different ratios. By altering the feed ratio, hydrogels were synthesized to have lower critical solution temperature close to physiological temperature. This ability to shift the phase transition temperature of PNVCL provides excellent flexibility in tailoring transitions to suit physiological temperature, inheriting great potential in drug delivery.     

Polymerization of lactams, 95 Preparation of polyesteramides by the anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone)

Preparation of polyesteramides-poly[(ε-caprolactam)-co-(ε-caprolactone)]s by anionic polymerization of ε-caprolactam in the presence of poly(ε-caprolactone) at 150 °C was studied in this paper. ε-Caprolactam magnesium bromide was used as an initiator of polymerization and polymeric materials containing 5-25 wt% ε-caprolactone units were obtained. Thermal methods (DSC and DMA) were employed for characterization of poly[(ε-caprolactam)-co-(ε-caprolactone)]s and their mechanical properties were also evaluated. By introducing the activator with N-acyllactam structure, the polymerization rate increased and it was possible to carry out the polymerization at 110 °C. Mechanical properties of polyesteramides were influenced by both the content of ε-caprolactone units incorporated into copolymer and polymerization temperature. The mechanism of incorporation of poly(ε-caprolactone) is discussed. The results show that it is not possible to restrict exchange transacylation reactions, progressing in the course of polymerization, by kinetic tools.