Resulting Block Copolymers Research Articles

Aliphatic polycarbonates with acid degradable ketal side groups as multi-pH-responsive immunodrug nanocarriers.

Pharmacokinetics and biodistribution profiles of active substances are crucial aspects for their safe and successful administration. Since many immunogenic compounds do not meet all requirements for safe and effective administration, well-defined drug nanocarrier systems are necessary with a stimuli-responsive drug-release profile. For this purpose, a novel pH-responsive aliphatic cyclic carbonate is introduced with benzyl ketal side chains and polymerized onto a poly(ethylene glycol) macroinitiator. The resulting block copolymers could be formulated via a solvent-evaporation method into well-defined polymeric micelles. The hydrophobic carbonate block was equipped with an acid degradable ketal side group that served as an acid-responsive functional group. Already subtle pH alternations led to micelle disassembly and the release of the active cargo. Furthermore, basic carbonate backbone degradation assured the pH responsiveness of the nanocarriers in both acidic and basic conditions. To investigate the delivery capacity of polymeric micelles, the model small molecule compound CL075, which serves as an immunotherapeutic TLR7/8 agonist, was encapsulated. Incubation studies with human blood plasma revealed the absence of undesirable protein adsorption on the drug-loaded nanoparticles. Furthermore, in vitro applications confirmed cell uptake of the nanodrug formulations by macrophages and the induction of payload-mediated immune stimulation. Altogether, these results underline the huge potential of the developed multi-pH-responsive polymeric nanocarrier for immunodrug delivery.

Customizing STEM organogels using PET-RAFT polymerization

PET-RAFT polymerization was used to modify STEM organogels, while degradable linkers enabled the characterization of the resulting block copolymers.

Synthesis and characterisation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) multi-block copolymers comprising blocks of differing 3-hydroxyvalerate contents

Polyhydroxyalkanoates (PHAs) are attractive alternatives to commodity petroleum derived plastics, being bacterially derived, thermoprocessible and truly biodegradable under ambient conditions. However, the common short chain length PHAs - poly(3-hydroxybutyrate) (P3HB) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) - are relatively stiff and brittle, and P3HB in particular has a narrow processing window. Block copolymer synthesis offers an opportunity to produce novel PHA materials comprised of different PHA phases, delivering a potential step-change improvement in PHA properties due to microphase separation. Therefore, this work demonstrates the synthesis and characterisation of novel high molecular weight PHBV-b-PHBV-b-PHBV block copolymers using isocyanate chemistry. High molecular weight, narrow compositional distribution, hydroxy-functionalised PHBV blocks of low (1 mol%) 3HV and high (67 mol%) 3HV contents were used as building blocks. The resulting block copolymers showed a very significant increase in elongation at break (to 76.0 %), as well as improved tensile toughness (to 15.0 MJ/m3) and tensile strength (to 18.5 MPa) compared to the starting materials or comparable blends. Based on the similarity in properties between the 1 mol% 3HV block copolymer products and their counterpart random copolymers, it is also shown that the introduction of urethane linkages had minimal effect on polymer properties. The morphologies of these novel PHBV materials were investigated, supporting the concept that the microphase separation of the different PHBV phases delivered these improved mechanical properties. This approach to PHA-b-PHA block copolymer synthesis offers an attractive generic platform for the production of novel biodegradable PHA materials for film and other applications.

Synthesis of Polyethylene Glycol-Poly(glycerol carbonate) Block Copolymeric Micelles as Surfactant-Free Drug Delivery Systems.

We report the synthesis of block copolymers of monomethoxylated polyethylene glycol and poly(glycerol carbonate) (mPEG-b-PGC) via the ring-opening polymerization of benzyl glycidyl ether, monomethoxylated polyethylene glycol, and carbon dioxide using a cobalt salen catalyst. The resulting block copolymers display high polymer/cyclic carbonate selectivity (>99%) and, if two oxirane monomers are used, random incorporation into the polymer feed. The resulting diblock mPEG-b-PGC polymer shows promise as a nanocarrier for surfactant-free, sustained chemotherapeutic delivery. mPEG-b-PGC, with paclitaxel conjugated to the pendant primary alcohol of the glycerol polymer backbone, readily forms 175 nm diameter particles in solution and contains 4.6 wt % paclitaxel (PTX), which is released over 42 days. The mPEG-b-PGC polymer itself is noncytotoxic, whereas the PTX-loaded nanoparticles are cytotoxic to lung, breast, and ovarian cancer cell lines.

Rhodamine B-Conjugated Fluorescent Block Copolymer Micelles for Efficient Chlorambucil Delivery and Intracellular Imaging.

The clinical development of the anticancer drug chlorambucil (CHL) is limited by its low solubility in water, poor bioavailability, and off-target toxicity. Besides, another constraint for monitoring intracellular drug delivery is the non-fluorescent nature of CHL. Nanocarriers based on block copolymers of poly(ethylene glycol)/poly(ethylene oxide) (PEG/PEO) and poly(ε-caprolactone) (PCL) are an elegant choice for drug delivery applications due to their high biocompatibility and inherent biodegradability properties. Here, we have designed and prepared block copolymer micelles (BCM) containing CHL (BCM-CHL) from a block copolymer having fluorescent probe rhodamine B (RhB) end-groups to achieve efficient drug delivery and intracellular imaging. For this purpose, the previously reported tetraphenylethylene (TPE)-containing poly(ethylene oxide)-b-poly(ε-caprolactone) [TPE-(PEO-b-PCL)2] triblock copolymer was conjugated with RhB by a feasible and effective post-polymerization modification method. In addition, the block copolymer was obtained by a facile and efficient synthetic strategy of one-pot block copolymerization. The amphiphilicity of the resulting block copolymer TPE-(PEO-b-PCL-RhB)2 led to the spontaneous formation of micelles (BCM) in aqueous media and successful encapsulation of the hydrophobic anticancer drug CHL (CHL-BCM). Dynamic light scattering and transmission electron microscopy analyses of BCM and CHL-BCM revealed a favorable size (10-100 nm) for passive targeting of tumor tissues via the enhanced permeability and retention effect. The fluorescence emission spectrum (λex 315 nm) of BCM demonstrated Förster resonance energy transfer between TPE aggregates (donor) and RhB (acceptor). On the other hand, CHL-BCM revealed TPE monomer emission, which may be attributed to the π-π stacking interaction between TPE and CHL molecules. The in vitro drug release profile showed that CHL-BCM exhibits drug release in a sustained manner over 48 h. A cytotoxicity study proved the biocompatibility of BCM, while CHL-BCM revealed significant toxicity to cervical (HeLa) cancer cells. The inherent fluorescence of RhB in the block copolymer offered an opportunity to directly monitor the cellular uptake of the micelles by confocal laser scanning microscopy imaging. These results demonstrate the potential of these block copolymers as drug nanocarriers and as bioimaging probes for theranostic applications.

Novel epoxy-terminated macromonomers and their polymerization for synthesis of bottle-brush type amphiphilic block copolymers.

Architecture of polymers has vital implications for their physical properties and applications. In this study, synthesis of a series of novel epoxy-terminated macromonomers namely Ep-DEGMME, Ep-TEGMME, Ep-EGMEE, Ep-EGMBE, and Ep-EGMHE is reported. The synthesized macromonomers vary in number of ethylene oxide units and length of the alkyl group. These macromonomers are first homopolymerized by anionic ring-opening polymerization for synthesis of homopolymers of a molar mass range. Subsequently, these macromonomers with different lengths of two segments (alkyl group and ethylene oxide units) are copolymerized with other monomers for synthesis of bottle-brush type architectures. In the first case, di- and tri-block copolymers of Ep-EGMBE are synthesized while using MeO-PEG or PEG as a macroinitiator; the resulting block copolymers have hydrophilic handle and hydrophobic brush. On the same lines, block copolymers of Ep-TEGMME with ε-caprolactone have hydrophobic handle and hydrophilic brush. The synthesized block copolymers are comprehensively characterized by SEC and liquid chromatography at critical conditions. The analysis reveals the successful synthesis of block copolymers while providing information on relative total molar mass, and individual block lengths of the block copolymers, along with amount of unwanted homopolymers in the sample.

Mesogen-jacketed liquid crystal like block copolymers: synthesis and self-assembly to prepare 1D PC thin films

One dimensional photonic crystals (1D PCs) show great potential application in light control, sensors and functional displays. Self-assembly of block copolymer is a facile method to prepare 1D PCs in large area and easy processing. However, due to the low refractive index of polymer and the chain entanglement at very high molecular weight, it is difficult to prepare 1D PCs by self-assembly of linear block copolymers. In this work, mesogen-jacketed liquid crystals like block copolymers with two different lumbar connected benzene terephthalate derivatives and polynorbornene backbone are designed and synthesized. The big steric hindrance of the mesogenic benzene terephthalate derivatives extends the polymer backbone to be rigid, and the resultant block copolymers are rapidly self-assembled into lamellar structures with big domain spacing. The refractive indexes of the two blocks is differentiated by selecting the phenyl and decyl substitute group of benzene terephthalate derivatives. Hence, 1D PCs are prepared by self-assembly of mesogen-jacketed liquid crystals like block copolymers. The maximum reflectance is ranged from ultraviolet to near infrared by increasing the polymerization degree of the block copolymers from 400 to 1400 gradually. The lamellar structures are characterized by cross section scanning electron microscope and small angle X ray scattering. Mesogen-jacketed liquid crystal like block copolymer is favored in 1D PC preparation for its facile synthesis and flexible structure design.

Synthesis and properties of ABA type triblock copolymer from poly(dimethylsiloxane) macroinitiator: Development of novel attachable initiators for atom transfer radical polymerization

A sequence of ABA-type polystyrene-b-poly(dimethylsiloxane)-b-polystyrene (PS-b-PDMS-b-PS) triblock copolymers were synthesized by ATRP (Atom Transfer Radical Polymerization) after appropriate end functionalization of vinyl terminated PDMS. Vinyl terminated PDMS was reacted with a 3-chloropropane thiol to synthesize a halo terminated macroinitiator. Subsequently, this macroinitiator was used to synthesize ABA-type block copolymers. The resulting block copolymers were characterized to confirm the presence of PDMS & PS blocks. The theoretical molecular weight and GPC was used to verify the high molecular weight of the ultimate block copolymer. The results show that the PS chains were successfully bound to the PDMS backbone and molecular weight linearly increased with time during the controlled polymerization. The functionality of the given polymer was confirmed by FT-IR analysis, 1H NMR, and 13C NMR spectra. The thermal stability increased after the addition of PS with PDMS. Additionally, the EDS analysis confirms the halogen content. DLS verified the particle size, whereas SEM was used for the morphology of the nanoaggregates. This triblock has good moisture resistance & thermal stability as determined by thermogravimetric analysis. The formation of PDMS blocks increased the hydrophobicity of the PS and contact angle analysis confirmed this.

Synthesis and Thermal Analysis of Non-Covalent PS-b-SC-b-P2VP Triblock Terpolymers via Polylactide Stereocomplexation.

Polylactides (PLAs) are thermoplastic materials known for their wide range of applications. Moreover, the equimolar mixtures of poly(L-Lactide) (PLLA) and poly(D-Lactide) (PDLA) can form stereocomplexes (SCs), which leads to the formation of new non-covalent complex macromolecular architectures. In this work, we report the synthesis and characterization of non-covalent triblock terpolymers of polystyrene-b-stereocomplex PLA-b-poly(2-vinylpyridine) (PS-b-SC-b-P2VP). Well-defined ω-hydroxy-PS and P2VP were synthesized by “living” anionic polymerization high-vacuum techniques with sec-BuLi as initiator, followed by termination with ethylene oxide. The resulting PS-OH and P2VP-OH were used as macroinitiators for the ring-opening polymerization (ROP) of DLA and LLA with Sn(Oct)2 as a catalyst to afford PS-b-PDLA and P2VP-b-PLLA, respectively. SC formation was achieved by mixing PS-b-PDLA and P2VP-b-PLLA chloroform solutions containing equimolar PLAs segments, followed by precipitation into n-hexane. The molecular characteristics of the resulting block copolymers (BCPs) were determined by 1H NMR, size exclusion chromatography, and Fourier-transform infrared spectroscopy. The formation of PS-b-SC-b-P2VP and the effect of molecular weight variation of PLA blocks on the resulting polymers, were investigated by differential scanning calorimetry, X-ray powder diffraction, and circular dichroism spectroscopies.

Self-immolative Amphiphilic Diblock Copolymers with Individually Triggerable Blocks.

Self-immolative polymers are a growing class of degradable polymers that undergo end-to-end depolymerization after the stimuli-responsive cleavage of an end-cap or backbone unit. Their incorporation into amphiphilic block copolymers can lead to functions such as the disintegration of copolymer nanoassemblies when depolymerization is triggered. However, diblock copolymers have not yet been developed where both blocks are self-immolative. Described here is the synthesis, self-assembly, and triggered depolymerization of self-immolative block copolymers with individually triggerable hydrophilic and hydrophobic blocks. Neutral and cationic hydrophilic polyglyxoylamides (PGAm) with acid-responsive end caps were synthesized and coupled to an ultraviolet (UV) light-triggerable poly(ethyl glyoxylate) (PEtG) hydrophobic block. The resulting block copolymers self-assembled to form nanoparticles in aqueous solution, and their depolymerization in response to acid and UV light was studied by techniques including light scattering, NMR spectroscopy, and electron microscopy. Acid led to selective depolymerization of the PGAm blocks, leading to aggregation, while UV light led to selective depolymerization of the PEtG block, leading to disassembly. This self-immolative block copolymer system provides an enhanced level of control over smart copolymer assemblies and their degradation.

Poly(ether ester) and related block copolymers via organocatalytic ring‐opening polymerization

AbstractPoly(p‐dioxanone) (PPDO) produced by ring‐opening polymerization (ROP) ofp‐dioxanone (PDO) has been attracted intensive attention in bioengineering and environmental materials due to the coexistence of ester and ether bonds in the repeating units. Herein, we systematically study the ROP behavior of PDO using classical organic amidine and guanidine compounds. The cyclic and linear PPDO homopolymers are efficiently produced and confirmed by the combination of1H,13C NMR and MALDI‐TOF MS spectra. Furthermore, triblock copolymers (PPDO‐b‐PCL‐b‐PPDO) containing poly(ε‐caprolactone) (PCL) as the soft segment and PPDO as the hard segment are prepared in the presence of ethylene glycol. The resultant block copolymers are well characterized using NMR, gel permeation chromatography, differential scanning calorimetry, and thermogravimetric analysis. It is found that the prepared triblock copolymers exhibit tunable flexibility, stabilization, hydrophilicity, and mechanical strength, which could be used as thermoplastic materials in biological and tissue engineering areas.

Synthesis of Biobased Block Copolymers Using A Novel Methacrylated Methyl Salicylate and Poly(3‐Hydroxybutyrate)

AbstractA novel biobased vinyl monomer was synthesized by the reaction of methyl salicylate with methacrylic anhydride. The resulting salicylate based monomer was polymerized by reversible addition fragmentation transfer (RAFT) polymerizations using two or three trithiocarbonate functionalized poly(3‐hydroxybutyrate) macro agents. The molecular structures of the obtained polymers were confirmed by NMR spectroscopy and GPC analysis. The resulting block copolymers showed glass transition temperature (Tg) at 5 °C and melting temperature (Tm) at 160 °C according to DSC results. Compared to PHB, the obtained block copolymers displayed enhanced thermal stability according to TGA results. The overall rate constants of the RAFT polymerization using tri‐functionalized PHB macro agent were determined as 2.58 ×10−4, 1.17×10−4, and 0.50×10−4 L mol−1s−1 for 70, 80 and 90 °C, respectively. The activation energy was found to be 18.6 kcal K−1mol−1. The overall rate constant of the homopolymerization of the obtained monomer was determined as 1.14×10−4 Lmol−1s−1.

Sterically Stabilized Polyionic Complex Nanogels of Chitosan Lysate and PEG-b-Polyglutamic Acid Copolymer for the Delivery of Irinotecan Active Metabolite (SN-38).

Poly Ionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers, such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups. Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH. Synthesis of PEG-b-PGlu was accomplished by N-carboxy anhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction. The resulting block copolymer was characterized by FTIR, 1H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating the formation of homogeneous spherical particles with a mean size of 28 nm at the PEGb- PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×103 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug. In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic conditions. Conclusively, the well-tuned PIC nanogels are suggested as a potentially biocompatible nanocarrier for SN38 delivery.

Synthesis of Block Copolymer Brush by RAFT and Click Chemistry and Its Self-Assembly as a Thin Film.

A well-defined block copolymer brush poly(glycidyl methacrylate)-graft-(poly(methyl methacrylate)-block- poly(oligo(ethylene glycol) methyl ether methacrylate)) (PGMA-g-(PMMA-b-POEGMA)) is synthesized via grafting from an approach based on a combination of click chemistry and reversible addition-fragmentation chain transfer (RAFT) polymerization. The resulting block copolymer brushes were characterized by 1H-NMR and size exclusion chromatography (SEC). The self-assembly of the block copolymer brush was then investigated under selective solvent conditions in three systems: THF/water, THF/CH3OH, and DMSO/CHCl3. PGMA-g-(PMMA-b-POEGMA) was found to self-assemble into spherical micelle structures as analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The average size of the particles was much smaller in THF/CH3OH and DMSO/CHCl3 as compared with the THF/water system. Thin film of block copolymer brushes with tunable surface properties was then prepared by the spin-coating technique. The thickness of the thin film was confirmed by scanning electron microscopy (SEM). Atom force microscopy (AFM) analysis revealed a spherical morphology when the block copolymer brush was treated with poor solvents for the backbone and hydrophobic side chains. The contact angle measurements were used to confirm the surface rearrangements of the block copolymer brushes.

Synthesis of Block Copolymers of Acrylic Acid and N-Butyl Acrylate under Reversible Chain-Transfer Conditions in a Water-Alcohol Medium

The laws of dispersion polymerization of n-butyl acrylate in an aqueous-alcoholic medium in the presence of a hydrophilic reversible addition-fragmentation chain-transfer poly(acrylic acid)-based polymeric agent with a trithiocarbonate group within the chain are investigated. It is shown that the portioned introduction of the monomer into the synthesis makes it possible to achieve higher maximum conversions. The resulting block copolymers are characterized by a relatively narrow molecular weight distribution and their number-average molecular weight increases linearly with increasing monomer concentration. The obtained dispersions of triblock copolymer poly(acrylic acid)–block-poly(n-butyl acrylate)–block-poly(acrylic acid) have a unimodal particle size distribution that persists after dialysis against water. It is shown that the synthesized dispersions may be used as a polymer matrix for immobilizing zinc oxide nanoparticles and as a polymer precursor in the process of the seeded polymerization of styrene.

Ethylene Polymerization‐Induced Self‐Assembly (PISA) of Poly(ethylene oxide)‐block‐polyethylene Copolymers via RAFT

AbstractPoly(ethylene oxide) (PEO) with dithiocarbamate chain ends (PEO–SC(=S)−N(CH3)Ph and PEO–SC(=S)−NPh2, named PEO‐1 and PEO‐2, respectively) were used as macromolecular chain‐transfer agents (macro‐CTAs) to mediate the reversible addition–fragmentation chain transfer (RAFT) polymerization of ethylene in dimethyl carbonate (DMC) under relatively mild conditions (80 °C, 80 bar). While only a slow consumption of PEO‐1 was observed, the rapid consumption of PEO‐2 led to a clean chain extension and the formation of a polyethylene (PE) segment. Upon polymerization, the resulting block copolymers PEO‐b‐PE self‐assembled into nanometric objects according to a polymerization‐induced self‐assembly (PISA).

Ethylene Polymerization-Induced Self-Assembly (PISA) of Poly(ethylene oxide)-block-polyethylene Copolymers via RAFT.

Poly(ethylene oxide) (PEO) with dithiocarbamate chain ends (PEO-SC(=S)-N(CH3 )Ph and PEO-SC(=S)-NPh2 , named PEO-1 and PEO-2, respectively) were used as macromolecular chain-transfer agents (macro-CTAs) to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization of ethylene in dimethyl carbonate (DMC) under relatively mild conditions (80 °C, 80 bar). While only a slow consumption of PEO-1 was observed, the rapid consumption of PEO-2 led to a clean chain extension and the formation of a polyethylene (PE) segment. Upon polymerization, the resulting block copolymers PEO-b-PE self-assembled into nanometric objects according to a polymerization-induced self-assembly (PISA).

One-Step Photocontrolled Polymerization-Induced Self-Assembly (Photo-PISA) by Using In Situ Bromine-Iodine Transformation Reversible-Deactivation Radical Polymerization.

Polymerization-induced self-assembly (PISA) has become an effective strategy to synthesize high solid content polymeric nanoparticles with various morphologies in situ. In this work, one-step PISA was achieved by in situ photocontrolled bromine-iodine transformation reversible-deactivation radical polymerization (hereinafter referred to as Photo-BIT-RDRP). The water-soluble macroinitiator precursor α-bromophenylacetate polyethylene glycol monomethyl ether ester (mPEG1k-BPA) was synthesized in advance, and then the polymer nanomicelles (mPEG1k-b-PBnMA and mPEG1k-b-PHPMA, where BnMA means benzyl methacrylate and HPMA is hydroxypropyl methacrylate) were successfully formed from a PISA process of hydrophobic monomer of BnMA or HPMA under irradiation with blue LED light at room temperature. In addition, the typical living features of the photocontrolled PISA process were confirmed by the linear increase of molecular weights of the resultant amphiphilic block copolymers with monomer conversions and narrow molecular weight distributions (Mw/Mn < 1.20). Importantly, the photocontrolled PISA process is realized by only one-step method by using in situ photo-BIT-RDRP, which avoids the use of transition metal catalysts in the traditional ATRP system, and simplifies the synthesis steps of nanomicelles. This strategy provides a promising pathway to solve the problem of active chain end (C-I) functionality loss in two-step polymerization of BIT-RDRP.

Unraveling the kinetics of the structural development during polymerization-induced self-assembly: decoupling the polymerization and the micelle structure

Upon extending a hydrophobic polymer chain from the end of a preceding hydrophilic chain in aqueous solutions, the resultant block copolymers may eventually undergo self-assembly.

Synthesis of bioactive polyaniline-b-polyacrylic acid copolymer nanofibrils as an effective antibacterial and anticancer agent in cancer therapy, especially for HT29 treatment.

In this work, a new highly water-soluble copolymer of polyacrylic acid with polyaniline is introduced. Acrylic acid was polymerized via the Reversible Addition Fragmentation Chain Transfer method (RAFT) in the presence of an initiator and the obtained polyacrylic acid was copolymerized with aniline at room temperature. As the main achievements of this work, the resulting block copolymer with nanosized structure revealed favorable solubility in polar solvents, as well as excellent antibacterial and anticancer activities. Therefore, it is an appropriate candidate for medical applications such as wound healing and cancer therapy, especially in HT29 treatment.