Synthesis and characterization of amphiphilic poly(ɛ-caprolactone)-b-polyphosphoester diblock copolymers bearing multifunctional pendant groups

A series of parent block copolyesters poly(?-caprolactone)-block-poly[2-(2-oxo-1, 3, 2-dioxaphospholoyloxy)ethyl acrylate] (PCL-b-POPEA) with different block lengths have been synthesized by ring-opening polymerization (ROP) and four kinds of mercaptans were then used in the postpolymerization modification via Michael-type addition reaction, resulting in several block copolyesters with various functionalities (e.g., hydroxyl, carboxyl, amine, and amino acid) in their pendant groups. The chemical structures of these block copolymers were characterized by FT-IR, NMR spectroscopy and GPC analysis. The self-assembly behaviors of PCL-b-POPEA have been studied by fluorescence probe technique, transmission electron microscopy (TEM) and high-performance particle size (HPPS) instrument. In vitro cytotoxicity test indicated that the block copolymers possess good biocompatibility. Initial in vitro drug loading and release studies using Doxorubicin (DOX) as a model drug demonstrated a faster release in the presence of phosphodiesterase I as compared to the system without enzyme. Moreover, it was found that DOX-loaded nanoparticles displayed higher inhibition to KB cell proliferation in comparison with free DOX. Therefore, the combination of ROP and Michael-type addition reaction provides a general access to various types of multifunctional and biodegradable materials.     

Synthesis and characterization of a novel amphiphilic poly (ethylene glycol)–poly (ε-caprolactone) graft copolymers

A series of amphiphilic graft copolymers PEO-g-PCL with different poly (ε-caprolactone) (PCL) molecular weight were successfully synthesized by a combination of anionic ring-opening polymerization (AROP) and coordination-insertion ring-opening polymerization. The linear PEO was produced by AROP of ethylene oxide (EO) and ethoxyethyl glycidyl ether initiated by 2-(2-methoxyethoxy) ethoxide potassium, and the hydroxyl groups on the backbone were deprotected after hydrolysis. The ring-opening polymerization of CL was initiated using the linear poly (ethylene oxide) (PEO) with hydroxyl group on repeated monomer as macroinitiator and Sn(Oct)₂ as catalyst, then amphiphilic graft copolymers PEO-g-PCL were obtained. By changing the ratio of monomer and macroinitiator, a series of PEO-g-PCL with well-defined structure, molecular weight control, and narrow molecular weight distribution were prepared. The expected intermediates and final products were confirmed by ¹H NMR and GPC analyzes. In addition, these amphiphilic graft copolymers could form spherical aggregates in aqueous solution by self-assemble, which were characterized by transmission electron microscopy, and the critical micelle concentration values of graft copolymers PEO-g-PCL were also examined in this article.     

Synthesis of graft copolymers of poly(methacrylic acid)-g-poly(ɛ-caprolactone) by coupling ROP and RAFT polymerizations

The aim of this study was to synthesize graft copolymers of poly(methacrylic acid)-g-poly(?-caprolactone) by a two-step process. In a first part, a macromonomer of 2-hydroxyethylmethacrylate-poly(?-caprolactone) (HEMA-PCL) was synthesized by coordinated anionic Ring Opening Polymerization (ROP). Then graft copolymers were obtained via Reversible Addition Fragmentation chain Transfer (RAFT) copolymerization of HEMA-PCL macromonomer and methacrylic acid (MAA).This two-step synthesis is a really interesting way to adjust and control parameters such as graft density, polymerization degree, copolymer composition, graft length, in order to adapt the final graft copolymers to their future applications. The efficiency of such copolymers in dispersing calcium carbonate into an unsaturated polyester resin has been point out by viscosity measurements.     

Preparation and characterization of poly(ɛ-caprolactone) nonwoven mats via melt electrospinning

Laser melt electrospinning is a novel technology to produce nonwoven scaffolds for tissue engineering (TE) applications. This solvent-free process is far safer than common solution electrospinning. In this paper, we demonstrated the poly(?-caprolactone) (PCL) fibers diameters could be governed from 3 to 12 μm with changing electrospinning parameters. The various diameters can meet the needs of scaffold properties such as porosity, pore size, etc. Our experiential results also showed that the fibers diameter tended to decrease as laser current increased. The degradation of PCL molecular chains often occurs in the melt electrospinning process due to mechanical scission and thermal degradation. The crystallinity of as-spun PCL fibers was approximately equal to that of the annealing fibers by X-ray diffraction (XRD) and differential scanning calorimetry (DSC). In our experiential, the collected PCL electrospun fibers often fused together to form a three-dimension network structure, which is favorable to mechanical properties.     

Miscibility of poly(styrene-co-vinyl phenol) with poly(ɛ-caprolactone)

Summary Poly(styrene-co-vinyl phenol) (STVPh)/poly(-caprolactone)(PCL) blends showed enhanced miscibility over polystyrene/PCL blend, and showed single glass transition temperature when the contents of vinyl phenol (VPh) in copolymer were higher than 10 wt % (maximum content of VPh in STVPh used in this study was 20 wt%). STVPh 4, STVPh 7, STVPh 10 (4, 7, 10 were VPh wt%)/PCL blends showed cloud points on heating for miscible blend system, and this phase separation was reversible on cooling. From melting point depression of PCL, interaction parameter, B. for miscible STVPh 12/PCL blend system was evaluated.     

Stereocomplex formation in enantiomeric diblock and triblock copolymers of poly (ɛ-caprolactone) and polylactide

Summary Enantiomeric diblock and triblock copolymers from caprolactone and lactide with various compositions were synthesized using alcohol/tin octoate as initiator system. Stereocomplexes were formed between pairs of enantiomeric block copolymers and their thermal properties examined. The melting temperatures of the crystalline PCL and PLA phases are depending on the composition of block copolymers. A raise of approximately 55°C of the temperature of PLA phase is observed in the blends as a consequence of stereocomplex formation as well in diblock as in triblock copolymers. Received: 31 July 2000/Revised version: 11 October 2000/Accepted: 26 October 2000     

Nanosized micelles self-assembled from amphiphilic poly(citric acid)–poly(ε-caprolactone)–poly(citric acid) copolymers

In this study, novel ABA-type amphiphilic copolymers consisting of poly(citric acid) (PCA) (A) as hydrophilic segment and poly(ε-caprolactone) (PCL) (B) as hydrophobic block were prepared by an approach in the following two steps: (1) ring-opening polymerization (ROP) of ε-caprolactone with 1,5-pentanediol initiator to obtain a hydroxyl telechelic PCL; (2) melt polycondensation reaction of hydroxyl telechelic PCL and citric acid molecules. The prepared copolymers are capable of self-assembling into nanosized micelles in aqueous solution. The influence of the copolymer composition on the micelle dimensions was investigated. The critical micellar concentration of the copolymers is in the range of 5–6.3 × 10^?2 mg/mL which is determined by the fluorescence probe technique using pyrene. Also the results indicate that CMC of self assembled micelles is influenced by the hydrophilicity of PCA–PCL–PCA copolymers depending on the CA/CP ratio, and these micelles may find great potential as drug carriers in biomedical fields.     

Synthesis of amphiphilic macrocyclic graft copolymer consisting of a poly(ethylene oxide) ring and multi-poly(?-caprolactone) lateral chains

A series of amphiphilic macrocyclic graft copolymers composed of a hydrophilic poly(ethylene oxide) as ring and hydrophobic poly(?-caprolactone) as lateral chains with different grafting lengths and densities of side chains were prepared by a combination of anionic ring-opening polymerization and coordination-insertion ring-opening polymerization. The anionic ring-opening copolymerization of ethylene oxide (EO) and ethoxyethyl glycidyl ether (EEGE) was carried out first using triethylene glycol and diphenylmethyl potassium (DPMK) as co-initiators, and a linear α,ω-dihydroxyl poly(ethylene oxide) with pendant protected hydroxymethyls (l-poly(EO-co-EEGE)) was obtained. The monomer reactivity ratios of these compounds are r_1(EO) = 1.20 ± 0.01 and r_2(EEGE) = 0.76 ± 0.02, respectively. Then the ring closure of l-poly(EO-co-EEGE) was achieved via an ether linkage by reaction with tosyl chloride (TsCl) in the presence of solid KOH. The crude cyclized product containing the linear chain-extended polymer was hydrolyzed in acidic conditions first and then purified by treating with α-CD. The pure cyclic copolymer of EO and glycidol (Gly) with multipendant hydroxymethyls [c-poly(EO-co-Gly)] as the macroinitiator was used further to initiate the ring-opening polymerization of ?-caprolactone (CL), and a series of amphiphilic macrocyclic graft copolymers c-PEO-g-PCL were obtained. The final products and intermediates were characterized by GPC, NMR and MALDI-TOF in detail.     

Synthesis and characterization of amphiphilic PLA-(PαN3CL-g-PBA) copolymers by ring-opening polymerization and click reaction

The present study prepared novel amphiphilic block-graft PDLLA-b-(PαN₃CL-g-PBA) and PLLA-b-(PαN₃CL-g-PBA) functional polyesters, containing a hydrophilic poly(α-azido-ε-caprolactone-graft-alkyne) (PαN₃CL-g-alkyne) segment and a hydrophobic poly(dl-lactide) (PDLLA) or poly(l-lactide) (PLLA) segment, using ring-opening polymerization of α-chloro-ε-caprolactone (αClCL) with a hydroxyl-terminated macroinitiator of PDLLA or PLLA, substituting pendent chloride with sodium azide. The copolymers were subsequently used for grafting of 2-propynyl-terminal benzoate moieties by way of Cu(I)-catalyzed Huisgen's 1,3-dipolar cycloaddition, thus producing a “click” reaction. Differential scanning calorimetry (DSC) and ¹H NMR, FT-IR, and GPC examined the characteristics of the copolymers. The critical micelle concentration (CMC) ranged from 2.7 mg L^?1 to 24.6 mg L^?1 at 25 °C and the average micelle size ranged from 106 nm to 297 nm. The length of the hydrophilic segment and the configuration of the lactide both influenced micelle stability. The micelle of PLLA-b-(PαN₃CL-g-PBA) provided high drug entrapment efficiency and loading content. The results from in vitro cell viability assays indicated that PLA-b-(PαN₃CL-g-PBA) shows low cytotoxicity.     

Slow release of levofloxacin conjugated on silica nanoparticles from poly(ɛ-caprolactone) nanofibers

Composite levofloxacin (LVF)/nanofibers have been fabricated through electrospinning. Slow release was achieved by covalently binding LVF to mesoporous silica nanoparticles (MSN) through a cleavable thioester bond and then blending the MSN into poly(?-caprolactone) (PCL) nanofibers. Conjugated LVF–MSN was characterized by FTIR, DSC, TGA, and solid-state C¹³ NMR. The structure of composite nanofibers was studied by scanning electron microscopy (SEM). Drug release profiles showed that burst release was decreased from 59% in the uniform PCL/LVF electrospun mats to 20% in the PCL/conjugated LVF–MSN mats after 1 day in phosphate buffer at 37°C, and gradual release in the latter was observed over the next 13 days. This slow release is due to the cleavable bond between LVF and MSN that can be hydrolyzed over a time and results in slow release of LVF. The results indicate that confining drug-conjugated MSN into nanofibers are effective ways to slow down the burst release of the drug.     

Synthesis of amphiphilic polycyclooctene-graft–poly(ethylene glycol) copolymers by ring-opening metathesis polymerization

In this paper, a novel monomer of 4-methyl-3-(carbamate)–carbanilic acid-4-cyclooctene ester (MCCCE) was synthesized and characterized by FTIR, NMR and ESI-MS. Polycyclooctene-graft-blocked isocyanate copolymers were prepared by the copolymerization of MCCCE and cyclooctene via ring-opening metathesis polymerization (ROMP). Amphiphilic polycyclooctene-graft–PEG copolymers were prepared by melt mixing the polycyclooctene-graft-blocked isocyanate copolymers with poly(ethylene glycol) (PEG) at 200 °C. The blocked isocyanate group on MCCCE can be dissociated to produce free isocyanate group, which will react with the end hydroxyl groups on PEG molecules. The effects of monomer-to-catalyst, monomer-to-chain transfer agent ratios on molecular weight of the copolymer were detailedly studied. The water contact angle of polycyclooctene-graft–PEG copolymer is much smaller than that of polycyclooctene.     

Synthesis of poly(N-isopropylacrylamide)-b-poly(ɛ-caprolactone) and its inclusion compound of β-cyclodextrin

Well-defined amphiphilic poly(N-isopropylacrylamide)-b-poly(ɛ-caprolactone) (PNIPAM-b-PCL) block copolymers have been successfully prepared in two steps. PNIPAMOH is firstly prepared by using 4,4′-azobis(4-cyano-1-pentanol) as bifunctional initiator, and then PNIPAM-b-PCL copolymer is synthesized via a ring-opening polymerization of CL using PNIPAMOH as a macro-initiator in the presence of stannous octoate as a catalyst. The PNIPAM-b-PCL copolymers self-assemble to form spherical micelles of 50–130 nm in diameter, which can be modulated by the chain length of PCL block. The inclusion complexes are fabricated by treating PNIPAM-b-PCL with β-cyclodextrin and they are characterized by infrared and ¹H NMR spectroscopies, X-ray powder diffraction, thermogravimetric analysis, and differential scanning calorimetry.     

Synthesis of poly(norbornene-g-ɛ-caprolactone) copolymers by sequential controlled ring opening polymerization

Summary Poly(norbornene-g-ɛ-caprolactone) copolymers have been prepared by the “grafting from” technique. Well controlled polynorbornene containing 5% acetate pendant groups has been firstly synthesized by ruthenium complex-mediated ring opening metathesis polymerization. The acetate groups have been derivatized into aluminum alkoxides by hydrolysis into alcohol followed by reaction of the alcohol with triethylaluminum. The two polymerization steps are under complete control, so that graft copolymers have been synthesized with a narrow molecular weight distribution and are free from any detectable traces of the parent homopolymers as stated by selective fractionation experiments. These original copolymers have been characterized by SEC, FTIR, ¹H NMR, DSC, TGA. Received: 28 January 1998/Revised version: 14 April 1998/Accepted: 14 April 1998     

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.     

Preparation of polystyrene poly(β-hydroxy nonanoate) graft copolymers

Summary Poly(-hydroxy nonanoate)-polystyrene graft copolymers were prepared by the reaction of active polystyrene containing peroxide group with poly(-hydroxy nonanoate) at 80°C. Graft copolymers with a wide graft composition range depending on the amount of active polystyrene in the original mixture were produced and separated from the grafting product by fractional precipitation. NMR and IR spectra of the graft copolymers were containing the characteristic bands of the corresponding blocks. DSC curves of the graft copolymers had a large endotherm between 50 and 110°C.This work was financially supported by KTU research fund and partly supported by TUBITAK Marmara Research Center.     

Synthesis and characterization of mid-chain macrophotoinitiator of poly(ε-caprolactone) by combination of ROP and click chemistry

Well-defined mid-chain functional macrophotoinitiator of poly(ε-caprolactone) (PCL-PI-PCL) was synthesized by combination of ring-opening polymerization (ROP) and click chemistry strategy. Dibromo functional photoinitiator (Br–PI–Br) was prepared by the condensation of 2-bromopropanoyl bromide with 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl propan-1-one (PI). Subsequently, terminal bromo groups in Br–PI–Br were converted to azido groups to form diazido functional photoinitiator (N₃–PI–N₃) using NaN₃. Well-defined precursor alkyne-functionalized PCL (alkyne-PCL) was prepared by ROP of ε-CL in the presence of propargyl alcohol as the initiator and stannous-2-ethylhexanoate (Sn(Oct)2) as the catalyst. Finally, the alkyne-functionalized PCL was coupled with N₃–PI–N₃ with high efficiency by click chemistry. The spectroscopic studies showed that low-polydispersity PCL with desired photoinitiator functionality in the middle of the chain was obtained.     

Synthesis,structure and behavior of new polycaprolactam copolymers based on poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) macroactivators derived from Pluronic block copolymers

Novel series of poly (CL–co–Pluronic) polymers were successfully synthesized in situ by ring-opening polymerization (ROP) of ε-caprolactam (ε-CL). The copolymerization was activated by new type macroactivators (MAs) based on hydroxyl-terminated poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) [PEO-PPO-PEO] triblock copolymers, known under the trade name Pluronic^®. Toluene-2,4-diisocyanate (TDI) was used to obtain the isocyanate-terminated Pluronic prepolymers. The corresponding MAs were synthesized in situ with an N-carbamoyllactam structure. As an initiator of the copolymerization processes was used sodium lactamate (NaCL). To confirm the influence over the copolymerization process, microstructure, composition and molecular weight of the polymeric products two new types MAs based on Pluronic (P123 and F68) have been varied from 2 to 10 wt.% (vs. the monomer ε-CL). The structure of the both Pluronic based macroactivators (MAs) and accordingly obtained two series poly (CL-co-Pluronic) polymers were confirmed by ¹H NMR and FT-IR analyses. Additionally, the structure, molecular weight, physicomechanical behavior, thermal stability and morphology of the new synthesized poly (CL–co–Pluronic) polymers have been investigated by Differential Scanning Calorimetry (DSC), Wide-Angle X-ray Diffraction (WAXD), Thermogravimetric Analysis (TGA) and Scanning Electron Microscopy (SEM) analysis.     

Synthesis of poly(tetrahydrofuran-b-ε-caprolactone) macromonomer via the Sml2-induced transformation

Summary A novel well-defined macromonomer consisting of different types of monomers in polymerization mechanisms was synthesized for the first time through the SmI₂-induced transformation. The macromonomer, -methacryloylpoly-(tetrahydrofuran-b--caprolactone), was prepared by the reaction of methacryloyl chloride with living poly(tetrahydrofuran-b--caprolactone) [poly(THF-b-CL)] which was obtained by the two-electron reduction of the cationic growing center of poly(THF) by samarium iodide (SmI₂) followed by the polymerization of CL. ¹H NMR analysis indicated the quantitative introduction of the methacryloyl group onto the polymer end. The molecular weight distribution of the macromonomer was relatively narrow, and the unit ratio of THF to CL could be controlled by both polymerization time of THF and the amount of CL, resulting from the living nature of both CL- and THF-polymerizations. Radical copolymerization of the produced macromonomers with methyl methacrylate in the presence of AIBN resulted in a polymethacrylate backbone grafted with poly(THF-b-CL) block copolymers.     

Sintered electrospun poly(ɛ-caprolactone)–poly(ethylene terephthalate) for drug delivery

Electrospinning has the inherent advantage of being able to achieve molecular mixing of polymers having substantially different melting points. Electrospun poly(ɛ-caprolactone)–poly(ethylene terephthalate) (PCL:PET) capsules are densified by sintering to enable drug encapsulation. Proton and diffusive nuclear magnetic resonance, as well as a selective dissolution, suggest an absence of reaction between the two polymers. Sintering at 100 °C successfully densifies 88.89:11.11 and 75:25 PCL:PET blends. Following sintering, the otherwise dense 75:25 composition retains electrospun features and exhibits some “memory” of its previous state. Sintering increases UTS approximately eightfold versus as-spun values for 88.89:11.11 and 75:25. Elongation increases sixfold and twofold and modulus 44- and 69-fold for the 75:25 and 88.89:11.11 samples, respectively. Differential scanning calorimetry suggests a postsintering structure of nanoscale PET dispersed in PCL along the original fiber directions. Selective PCL removal from dense blends shows that fibrous characteristics remain. An internal shish–kebab-like structure is also present in as-spun 75:25 PCL:PET. Water absorption of hydrophobic oil-containing capsules is approximately zero after 49 days. In contrast, hydrophilic (HPI) oils allow substantial water uptake. Unsurprisingly, there is no release of a model drug from the hydrophobic carrier. HPI oil provides linear (zero-order) release inversely proportional to PET from the 88.89:11.11 and 75:25 ratios. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47731.