Biodegradable poly(ether-ester) multiblock copolymers for controlled release applications: An in vivo evaluation

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate segments were evaluated for their in vivo degradation and biocompatibility in order to establish a correlation with previously reported in vitro results. Porous polymer sheets were implanted subcutaneously for 32 weeks in rats. The degradation was monitored visually (histology), by molecular weight (GPC), and by copolymer composition (NMR). Substitution of the aromatic terephthalate units by aliphatic succinate units was shown to accelerate the degradation rate of the copolymers. Direct correlation of the in vivo and in vitro degradation of the porous implants showed a slightly faster initial molecular weight decrease in vivo. Besides hydrolysis, oxidation occurs in vivo due to the presence of radicals produced by inflammatory cells. In addition, the higher molecular weight plateau of the residue found in vivo indicated a higher solubility of the oligomers in the extracellular fluid compared to a phosphate buffer. Minor changes in the poly(ether-ester) compositions were noted due to degradation. Microscopically, fragmentation of the porous implants was observed in time. At later stages of degradation, macrophages were observed phagocytozing small polymer particles. Both in vitro cytotoxicity studies and histology on in vivo samples proved the biocompatibility of the poly(ether-ester)s.     

Biodegradable poly(ethylene oxide)/poly(epsilon-caprolactone) multiblock copolymers.

A series of poly(ethylene oxide) (PEO)/poly(epsilon-caprolactone) (PCL) containing biodegradable poly(ether ester urethane)s, covering a wide range of compositions, were synthesized and characterized. The synthesis consisted of a two-step process. During the first step, the ring-opening reaction of epsilon-caprolactone was carried out, initiated by the hydroxyl terminal groups of the PEO chain. The second step involved the chain extension of these PCL-PEO-PCL trimers with hexamethylene diisocyanate. By varying either the ethylene oxide/epsilon-caprolactone ratio or the length of both segments, we obtained a series of polymers having different morphologies and displaying a broad range of properties.     

Biodegradable photo-crosslinked poly(ether-ester) networks for lubricious coatings

Biodegradable poly(ether-ester) networks were synthesized by UV photopolymerization and their lubrication performances were evaluated. Polyethers such as poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and poly(tetramethylene glycol) (PTMG) were copolymerized with oligomers of D,L-lactic acid and terminated with acrylate groups to form photopolymerizable macromers. 1H NMR and IR spectra confirmed the chemical structures of copolymers and diacrylated macromers. Crosslinked polymer networks were formed upon UV-initiated free-radical polymerization. Gel contents, water contents, and contact angles were measured to characterize the crosslinked networks. In vitro degradation times of the crosslinked networks at 37 degrees C in 1 N NaOH varied from 20 min to 7 days depending on the crosslinking density (molecular weight of macromer) and the hydrophilic susceptibility (types of polyethers). The crosslinked polymers were coated on stainless-steel needles to investigate the lubrication properties by measuring penetration and drag forces through rubber stoppers. The maximum improvement in penetration force over control was 41% in the needle coated with PPG-based polymer networks (molecular weight of PPG = 4000). These materials can potentially be used as biodegradable lubricants for coating various medical products to replace the existing non-degradable silicone-based materials currently used.     

Control of vitamin B12 release from poly(ethylene glycol)/poly(butylene terephthalate) multiblock copolymers

The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the wt% of PEGT. From permeation and release experiments. the diffusion coefficient of vitamin B12 through PEGT/PBT films of different compositions was determined. The diffusion coefficient of Vitamin B12 was strongly dependent on the composition of the copolymers. Although an increased wt% of PEGT (at a constant PEG-segment length) resulted in a higher diffusion coefficient, a major effect was observed at increasing PEG-segment length. By varying the copolymer composition, a complete release of vitamin B12 in 1 day up to a constant release for over 12 weeks was obtained. The release rate could be effectively tailored by blending copolymers with different PEG-segment lengths. The swelling and the crystallinity of the matrix could explain the effect of the matrix composition on the release behavior.     

Reverse thermo-responsive poly(ethylene oxide) and poly(propylene oxide) multiblock copolymers

Aiming at developing new reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene oxide) multiblock copolymers were synthesized by covalently binding the two components using carbonyl chloride and diacyl chlorides as the coupling molecules. The appropriate selection of the various components allowed the generation of systems displaying much enhanced rheological properties. For example, 15 wt% aqueous solutions of an alternating poly(ether-carbonate) comprising PEO6000 and PPO3000 segments, achieved a viscosity of 140,000 Pas, while the commercially available Pluronic F127 displayed 5,000 Pas only. Furthermore, the structure of the chain extender played a key role in determining the sol-gel transition. While poly(ether-ester)s containing therephtaloyl (para) and isophtaloyl (metha) coupling units failed to gel at any concentration, a 15 wt% aqueous solution of the polymer chain-extended with phtaloyl chloride (ortho) gelled at 43 degrees C. The water solutions were also studied by dynamic light scattering and a clear influence of the PEO/PPO ratio on the aggregate size was observed. By incorporating short aliphatic oligoesters into the backbone, prior to the chain extension stage, reverse thermal gelation-displaying biodegradable poly(ether-ester-carbonate)s, were generated.     

Synthesis and characterization of multiblock copolymers poly[poly(L-lactide)-block-polydimethylsiloxane]

The preparation of multiblock copolymers poly[poly(L -lactide)-block-polydimethylsiloxane] by polycondensation of bifunctional oligomers via hydrosilylation is described. The procedure consists first to synthesize the two bifunctional oligomers α,ω-disilyl-polydimethylsiloxane and α,ω-diallyl-poly(L -lactide). The former is prepared in one step by cationic polymerization of octamethylcyclotetrasiloxane in the presence of 1,1,3,3-tetramethyldisiloxane as end-blocker. Two steps are necessary to prepare α,ω-diallyl-poly(L -lactide). The first one is the polymerization of L-lactide initiated by the system ethylene glycol/tin 2-ethylhexanoate. In a second step, the hydroxyl end-groups of the resulting α,ω-dihydroxy-poly(L -lactide) are transformed, by reaction with allyl isocyanate, into terminal allylic functions. Different multiblock copolymers were prepared by hydrosilylation (catalyzed by hexachloroplatinic acid) using the same α,ω-diallyl-poly(L -lactide) (M?_n = 2000 g · mol ^?1) and various α,ω-disilyl-polydimethylsiloxanes (M?_n from 1 750 to 9 000 g · mol ^?1). The influence of parameters such as temperature, stoichiometry of reactive end-groups and catalyst concentration on the molecular weight of the copolymers was studied. High molecular weight copolymers were obtained (DP_n > 12 by SEC). In addition to the biodegradability of the lactic acid units, the immiscibility of the polydimethylsiloxane and poly(L -lactide) blocks imparts thermoplastic elastomer properties to these copolymers. The crystallinity of the poly(L -lactide) phase is dependent on the molecular weight of the polydimethylsiloxane blocks.     

Biodegradable block poly(ester-urethane)s based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymers

A series of block poly(ester-urethane)s (abbreviated as PU3/4HB) based on biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) segments were synthesized by a facile way of melting polymerization using 1,6-hexamethylene diisocyanate (HDI) as the coupling agent and stannous octanoate (Sn(Oct)(2)) as catalyst, with different 4HB contents and segment lengths. The chemical structure, molecular weight and distribution were systematically characterized by (1)H nuclear magnetic resonance spectrum (NMR), Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC). The thermal property was studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The hydrophilicity was investigated by static contact angle of deionized water and CH(2)I(2). DSC curves revealed that the PU3/4HB polyurethanes have their T(g) from -25.6?°C to -4.3?°C, and crystallinity from 2.5% to 25.3%, being almost amorphous to semi-crystalline. The obtained PU3/4HBs are hydrophobic (water contact angle 77.4°-95.9°), and their surface free energy (SFE) were studied. The morphology of platelets adhered on the polyurethane film observed by scanning electron microscope (SEM) showed that platelets were activated on the PU3/4HB films which would lead to blood coagulation. The lactate dehydrogenase (LDH) assay revealed that the PU3/4HBs displayed higher platelet adhesion property than raw materials and biodegradable polymer polylactic acid (PLA) and would be potential hemostatic materials. Crystallinity degree, hydrophobicity, surface free energy and urethane linkage content play important roles in affecting the LDH activity and hence the platelet adhesion. CCK-8 assay showed that the PU3/4HB is non-toxic and well for cell growth and proliferation of mouse fibroblast L929. It showed that the hydrophobicity is an important factor for cell growth while 3HB content of the PU3/4HB is important for the cell proliferation. Through changing the composition and the chain-length of P3/4HB-diol prepolymers, the biocompatibility of the poly(ester-urethane)s can be tailored.     

PEO-PPO-PEO-based poly(ether ester urethane)s as degradable reverse thermo-responsive multiblock copolymers

Aiming at developing biodegradable thermo-responsive polymers that display enhanced rheological properties, a family of PEO-PPO-PEO based poly(ether ester urethane)s, was developed. The materials were produced following a two-step synthetic pathway. The PEO-PPO-PEO triblocks were first end-capped with LA or CL oligo(ester)s whereby pentablocks were produced. Then, the different precursors were chain extended using hexamethylene diisocyanate to create the respective polymers. The length and type of the ester block influenced the behavior of the molecules in water, especially their viscosity versus temperature response. The gelation temperature increased from 23 degrees C for a 20wt% F127 solution to 26 and 31 degrees C for pentablocks with 4.4 and 7.5 lactoyl units, respectively. Materials containing longer LA units failed to show any reverse thermo-responsiveness. The presence of the oligo(ester) blocks also reduced the viscosity of the gel at 37 degrees C. While F127 displayed a viscosity of around 28,000Pas, pentablocks containing 4.4 and 7.5 LA units showed values of 15,400 and 12,600Pas. Also, the viscosity at 37 degrees C as well as the gelation temperature decreased as the molecular weight of the oligo(ester)s increased. Finally, the degradation process of the gels was studied by monitoring their viscosity at body temperature and determining the molecular weight of the polymers, over time. Polymers were tailored so to combine high initial viscosity values with diverse degradation rates, as a function of the length and type of the oligo(ester) present along the polymeric backbone.     

Biodegradable drug carriers based on poly(ethylene glycol) block copolymers

The synthesis of a model water-soluble drug carrier system based on poly(ethylene glycol) (PEG) block copolymers is described. In the system, two blocks of PEG are connected via a biodegradable oligopeptide or amino acid linkage incorporating at least one glutamic acid residue. A drug model (4-nitroaniline) is attached to the γ-carboxyl group of glutamic acid of the polymer carrier via an enzymatically degradable oligopeptide spacer. All oligopeptides were prepared as potential substrates for cathepsin B, a representative of lysosomal enzymes. The relationship between the structure of oligopeptides forming the linkage between two PEG molecules and the rate of cathepsin B-catalyzed polymer chain degradation is evaluated. The relationship between the structure of the spacer and kinetics of drug model release from the carrier after incubation in cathepsin B solution is also discussed in detail. The results show that, by altering the structure of oligopeptides in the polymer construct, marked changes in the rate of both polymer degradation and the drug model release can be achieved.     

Biodegradable poly(L-lactide)-poly(ethylene glycol) multiblock copolymer: synthesis and evaluation of cell affinity

A series of poly(L-lactide)-poly(ethylene glycol) multiblock copolymers (Multi-PLE) with high molecular weight were synthesized and successfully used to fabricate three-dimensional scaffolds. Using mouse NIH 3T3 fibroblasts as model cells, the cell affinity of various Multi-PLE copolymers was evaluated and compared with that of poly(L-lactide) (PLLA) by means of cell attachment efficiency measurement, scanning electron microscopy observation and MTT assay. On one hand, the results showed that the cell attachment efficiency on Multi-PLE 4/1(4/1 refers to the molar ratio of lactidyl units to ethylene oxide units) films was close to that on PLLA film, however, the other Multi-PLE films exhibited much lower cell attachment efficiency than PLLA film, such as Multi-PLE 2/1 and Multi-PLE 1/1, which had higher PEG content. On the other hand, it was interesting to find that cell proliferation on Multi-PLE4/1 and Multi-PLE2/1 scaffolds was better than that on PLLA scaffold, which was closely related to the improved hydrophilicity of Multi-PLE copolymers due to the incorporation of PEG in comparison with pure PLLA. The Multi-PLE copolymer scaffolds with appropriate hydrophilicity were in favor of mass transportation, and then of cell proliferation and cell affinity. It meant that the cell proliferation would be much improved by increasing the hydrophilicity of the three-dimensional scaffolds, which even outweighed the disadvantages of the cell attachment efficiency reduction with the incorporation of PEG.     

Biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol) block copolymers: characterization and their use as drug carriers for a controlled delivery system

Poly(epsilon-caprolactone)-poly(ethylene glycol) (PECL) copolymers were synthesized from polyethylene glycol (PEG) and epsilon-caprolactone (epsilon-CL) using stannous octoate as catalyst at 160 degrees C by bulk polymerization. The effect of the molecular weight of PEG and the copolymer ratio on the properties of the copolymers was investigated by (1)H-NMR, IR, DSC and GPC. PCL and PECL microspheres containing human serum albumin were elaborated by solvent extraction method based on the formation of double w/o/w emulsion. Microspheres were characterized in terms of morphology, size, loading efficiency, and the efficiency of microspheres formation. The results show that the microspheres prepared from PECL-10 and PECL-15 copolymers achieved the highest loading efficiency (about 50%) among all copolymers. These results indicate that the properties of copolymers could be tailored by adjusting polymer composition. It is suggested that these matrix polymers may be optimized as carriers in the protein (antigen) delivery system for different purposes.     

Biodegradable poly(ethylene glycol) hydrogels crosslinked with genipin for tissue engineering applications

In this study amino-terminated poly(ethylene glycol) (PEG-diamine) hydrogels were crosslinked with genipin, a chemical naturally derived from the gardenia fruit. Dissolution, swelling, and PEG-genipin release properties were determined. The dissolution studies indicated that the hydrogels are water soluble, and that the dissolution rate was concentration, mass, and temperature dependent. The dissolution rates are easily tailored from 3 min to >100 days. The PEG-genipin release study indicated that the greatest release occurs within the first 24 h of immersion in water, and that incubation at 37 degrees C elicits a greater initial release than samples incubated at room temperature for all genipin concentrations. Through scanning electron microscopy it was observed that the hydrogels are porous, and surface morphology changes before and after swelling. Furthermore, smooth muscle cell (SMC) adhesion studies indicated that the PEG-genipin hydrogel is a suitable substrate for SMC seeding. Overall, the results of these studies indicate that PEG-genipin hydrogels may provide potential scaffolding for a variety of tissue engineering applications.     

In vitro and ex vivo platelet interactions with hydrophilic-hydrophobic poly(ethylene oxide)-polystyrene multiblock copolymers

Hydrophilic-hydrophobic multiblock copolymers synthesized from telechelic oligomers of poly(ethylene oxide) (PEO) and polystyrene (PS) have been used to study the influence of hydrophilic and hydrophobic balance on interfacial interactions of these surfaces with blood components. In vitro coagulation assays show no inherent ability of these amphiphilic surfaces to affect contact activation or coagulation factors. In vitro platelet adhesion and release reactions from rabbit platelet-rich plasma were shown to be greatest on Biomer and PS homopolymer surfaces and least on cross-linked PEO surfaces, with the PEO-PS block copolymers demonstrating intermediate responses. These same substrates were tested in a new low-flow, low-shear arterio-artery shunt system in rabbits. Whole blood occlusion times were not a direct function of hydrophilic content as both PEO and PS homopolymers and Biomer showed short occlusion times, while PEO-PS block copolymers prolonged occlusion times considerably, depending on composition. Overall, results suggest that PEO-PS block copolymers promote unique whole blood responses in contrast to homopolymer and Biomer controls which are more complex than direct correlations to bulk hydrophilic and hydrophobic contents.     

Macroporous poly(sucrose acrylate) hydrogel for controlled release of macromolecules

We have studied the controlled release of proteins from poly(sucrose acrylate) hydrogels. The hydrogels were prepared by a two-step procedure in which sucrose was first acylated to sucrose-1′-acrylate followed by free radical polymerization. By adjusting the cross-link ratio and initial monomer concentration, the swelling ratio of the hydrogel was varied from five to 28. The mechanical strength of these hydrogels was comparable to that of other hydrogels with approximately the same swelling ratio. Scanning electron micrographs and mesh size calculations indicate that the hydrogel is macroporous, suggesting it may be suitable for a variety of biomedical applications. The release kinetics of β-lactoglobulin, bovine serum albumin and γ-globulin were studied as a function of initial monomer concentrations for the sucrose-based hydrogel. All of the release profiles were characterized by an initial burst of protein in the first 25 h followed by a long period of sustained release (s> 500 h). The magnitude of the initial burst was reduced by increasing the initial monomer concentration and by increasing the molecular weight of the protein. A quantitative model based on the heterogeneous nature of the hydrogel was developed to explain the observed release kinetics.     

A novel two-level microstructured poly(N-isopropylacrylamide) hydrogel for controlled release

The aim of this work was to demonstrate that conventional poly(N-isopropylacrylamide) (PNIPAAm) hydrogels can improve their shrinkage and release properties solely due to the introduction of a heterogeneous density fluctuation-based microstructure. To this end, a novel structurally engineered PNIPAAm hydrogel was designed and compared with a chemically similar, but homogeneous, PNIPAAm hydrogel reference. For the two-step preparation PNIPAAm microgels were firstly synthesized with surface amine groups and further functionalized with polymerizable acrylate groups. In the second step the microgels, themselves acting as crosslinkers, were crosslinked to form a bulk network by inter-connecting the microgels with linear PNIPAAm chains. Although the chemical composition of the newly prepared hydrogel was generally the same as conventional PNIPAAm hydrogels (a relative control), significantly improved shrinkage properties and a more efficient “on–off” switching induced by temperature modulations were observed for the novel gel as compared with the homogeneous reference. These improved shrinkage properties were ascribed to the novel structure, which is believed to enable rapid shrinking of the small microgel crosslinkers and, thereupon, the generation of a sufficient number of diffusion channels for quick water release. Rhodamine B and ibuprofen (IBU) as model compounds were completely released from this novel gel at 20 °C, whereas at temperatures above the lower critical solution temperature release stopped after initial 40% and 70% “bursts” for rhodamine B and IBU, respectively, due to shrinkage of the gel network. This approach may provide an avenue to design temperature-sensitive drug delivery systems with state of the art switching properties and fast release kinetics by combining the here presented innovative strategy with complementary enhancements, such as the introduction of porosity.     

Properties of extruded poly(tetramethylene oxide)-polyurethane block copolymers for blood-contacting applications

The bulk and surface properties and blood compatibility of a series of polyurethanes based on methylene bis(p-phenyl isocyanate), 1,4-butanediol, and poly(tetramethylene oxide) of molecular weight 1000 were studied. The hard-to-soft segment ratio of these multiphase polymers was varied, and the effect of substituting a poly(dimethylsiloxane)-containing polyol in place of 5% of the polyether soft segment was studied. Bulk properties such as tensile strength and modulus increased with hard segment content, as did surface wettability and ESCA nitrogen content. However, blood compatibility measured by a canine ex vivo blood-contacting experiment was not found to vary with hard/soft segment ratio. The addition of the silicone-containing polyol did not significantly lower the surface wettability, although ESCA-measured silicon content increased and physical properties were unfavourably affected by the incorporation of this co-soft segment. Incorporation of the siloxane-containing component resulted in increased platelet adhesion and fibrinogen deposition at most blood contact times in comparison with the other polyurethanes.     

Biodegradable nanoparticles of amphiphilic triblock copolymers based on poly(3-hydroxybutyrate) and poly(ethylene glycol) as drug carriers

New amorphous amphiphilic triblock copolymers of poly(3-hydroxybutyrate)-poly(ethylene glycol)-poly(3-hydroxybutyrate) (PHB-PEG-PHB) were synthesized using the ring-opening copolymerization of beta-butyrolactone monomer. They were characterized by fluorescence, SEM and (1)H NMR. These triblock copolymers can form biodegradable nanoparticles with core-shell structure in aqueous solution. Comparing to the poly(ethylene oxide)-PHB-poly(ethylene oxide) (PEO-PHB-PEO) copolymers, these nanoparticles exhibited much smaller critical micelle concentrations and better drug loading properties, which indicated that the nanoparticles were very suitable for delivery carriers of hydrophobic drugs. The drug release profile monitored by fluorescence showed that the release of pyrene from the PHB-PEG-PHB nanoparticles exhibited the second-order exponential decay behavior. The initial biodegradation rate of the PHB-PEG-PHB nanoparticles was related to the enzyme amount, the initial concentrations of nanoparticle dispersions and the PHB block length. The biodegraded products detected by (1)H NMR contained 3HB monomer, dimer and minor trimer, which were safe to the body.     

Biodegradable micelles with sheddable poly(ethylene glycol) shells for triggered intracellular release of doxorubicin

Biodegradable micelles with sheddable poly(ethylene glycol) shells were developed based on disulfide-linked poly(ethylene glycol)-b-poly(?-caprolactone) (PEG-SS-PCL) diblock copolymer and applied for rapid intracellular release of doxorubicin (DOX). PEG-SS-PCL was prepared with controlled block lengths via exchange reaction between PEG orthopyridyl disulfide and mercapto PCL. The micelles formed from PEG-SS-PCL, though sufficiently stable in water, were prone to fast aggregation in the presence of 10 mm dithiothreitol (DTT), due to shedding of the PEG shells through reductive cleavage of the intermediate disulfide bonds. Interestingly, the in vitro release studies revealed that these shell-sheddable micelles released DOX quantitatively within 12 h under a reductive environment analogous to that of the intracellular compartments such as cytosol and the cell nucleus. In contrast, minimal drug release (<20%) was observed within 24 h for the reduction insensitive PEG–PCL micelles under the same conditions as well as for PEG-SS-PCL micelles under the non-reductive conditions. Remarkably, cell experiments showed that these shell-sheddable micelles accomplished much faster release of DOX inside cells and higher anticancer efficacy as compared to the reduction insensitive control. These shell-sheddable biodegradable micelles are highly promising for the efficient intracellular delivery of various lipophilic anticancer drugs to achieve improved cancer therapy.     

Biodegradable hollow fibres for the controlled release of drugs

Biodegradable hollow fibres of poly-L-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug release was compared with the release in vitro using different release media. Fibres, disinfected with alcohol showed a zero-order release, both in vitro and in vivo, for over 6 months. Fibres, either gamma-sterilized or disinfected with alcohol were harvested at time intervals ranging from 1 d to 6 months after implantation. Molecular weights of PLLA, tensile strengths, and remaining amounts of drug were determined as a function of time. The tissue reaction can be described as a very moderate foreign body reaction with the initial presence of macrophages, which are gradually replaced by fibroblasts which form a collagen capsule. Molecular weight determinations of PLLA showed a decrease from an initial Mw of 1.59 X 10(5) to 5.5 X 10(4) in 4 months (after alcohol sterilization). A gradual decrease in fibre strength with time was observed which did not significantly impair the release rate of levonorgestrel.     

Synthesis and properties of well-defined multiblock copolymers: poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene

Well-defined poly(4,4′-isopropylidenediphenyl carbonate)-block-polystyrene multiblock copolymers, PC-b-PS, were prepared by condensation of PC prepolymers having chloroformyl end-groups with PS prepolymers having hydroxyl end-groups. Both prepolymers had narrow molecular weight distribution (PC prepolymer: M?_w/M?_n ≤ 1,31, PS prepolymer: M?_w/M?_n ≤ 1,03). The course of the polycondensation reaction depends on the molecular weight of the prepolymers used as substrates. After fractionation, the obtained multiblock copolymers are homogeneous in chemical composition and have a narrow molecular weight distribution. The mechanical properties of the copolymers depend on the weight fraction of the PS blocks. All copolymers exhibit two glass transition temperatures, close to those of the parent homopolymers.