Complexation of Amino‐Acid‐Based Block Copolymers With Dual Thermoresponsive Properties and Water‐Soluble Silsesquioxane Nanoparticles

Smart organic–inorganic hybrids are prepared using non‐covalent interactions between water‐soluble silsesquioxane nanoparticles and two amino acid‐based block copolymers prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. A block copolymer displaying lower critical solution temperature (LCST) and upper critical solution temperature (UCST) is employed, in which only poly(N‐acryloyl‐4‐trans‐hydroxy‐L ‐proline) segment could interact with the nanoparticles, whereas another poly(N‐acryloyl‐L ‐proline methyl ester) segment shows a thermoresponsive property without any interaction. The complexation of another type of dual thermosensitive block copolymer with two different LCSTs and the silsesquioxane nanoparticles is also investigated.     

Temperature and pH dependence of the catalytic activity of colloidal platinum nanoparticles stabilized by poly[(vinylamine)‐co‐(N‐vinylisobutyramide)

Colloidal platinum nanoparticles in the size range of 5–35 Å have been successfully prepared in water at room temperature by NaBH₄ reduction of ionic platinum in the presence of poly[(vinylamine)‐co‐(N‐vinylisobutyramide)] (PVAm‐co‐PNVIBA). To our knowledge, the temperature‐ and pH‐responsive copolymer was used for the first time as the stabilizer of colloidal metal particles. Three PVAm‐co‐PNVIBA copolymers with PVAm contents of 4.1, 8.3, and 19.8 mol‐% were examined. The particle size and morphology of the platinum colloids varied with the copolymer composition, as confirmed by TEM measurements. The polymer‐stabilized Pt nanoparticles precipitated on heating above their critical flocculation temperatures (CFTs), which were strongly dependent on the solution pH and the copolymer composition. The CFTs were 0.2–1.6°C lower than the lower critical solution temperatures (LCSTs) of the copolymers free in water and the differences increased with increasing PVAm content. The catalytic activity of the Pt nanoparticles was investigated in the aqueous hydrogenation of allyl alcohol. It was found that the activity was regulated through temperature‐ and pH‐induced phase separation. The PVAm content also strongly effected the catalytic activity and the morphology of phase separated catalysts. With a PVAm content of 4.1 mol‐%, the colloidal platinum sol reversibly changed its catalytic activity with changes in temperature.     

Modification of Microbial Polymalic Acid With Hydrophobic Amino Acids for Drug‐Releasing Nanoparticles

Microbial poly(β,L ‐malic acid) was modified with either L ‐leucine ethyl ester (L) or L ‐phenylalanine methyl ester (F) to produce amphiphylic copolymers. The degradation of these copolymers in aqueous buffer took place under physiological conditions in a few weeks by hydrolysis of the side chain ester group followed by cleavage of the main chain. Spherical nanoparticles with diameters ranging between 70 and 230 nm were prepared from these copolymers by the dialysis‐precipitation method. No alteration of the cell viability was observed after incubation of these nanoparticles in different cell lines. Anticancer drugs temozolomide and doxorubicin were encapsulated in the nanoparticles. Temozolomide was released within several hours whereas doxorubicin took several weeks to be completely liberated.     

New macromolecular micelles based on degradable amphiphilic block copolymers of malic acid and malic acid ester

To study the behaviour of polymeric materials under in‐vivo conditions, degradable macromolecular micelles based on amphiphilic block copolymers of poly(β‐malic acid) as hydrophilic units and poly(β‐malic acid alkyl esters) as hydrophobic blocks are studied. First three β‐substituted β‐lactones, benzyl malolactonate, butyl malolactonate, and butyl 3‐methylmalolactonate were prepared, starting from aspartic acid. A prepolymer based on benzyl malate units was synthesized by anionic ring‐opening polymerization of benzyl malolactonate. Then the carboxylic end groups of this prepolymer were used as initiator for the polymerization of the second lactone, e. g. butyl malolactonate or butyl 3‐methylmalolactonate. The prepolymer and block copolymers have been characterized by ¹H NMR and size exclusion chromatography (SEC). Degradable macromolecular micelles were prepared from the block copolymers by two different methods and characterized by dynamic light scattering and fluorescence measurements using pyrene as a fluorescence probe. It was shown that these amphiphilic degradable copolymers form stable micelles under physiological conditions (10^–2 M phosphate buffered solution, PBS, pH 7.4 with 0.15 M NaCl). Moreover, it was displayed that the characteristics of these macromolecular micelles, especially the critical micellar concentration (cmc), are depending on the chain length of both blocks and on the chemical structure of the hydrophobic block. A very important conclusion of this study is, that micelle formation is dependent on the pH of the medium. Therefore, besides the fact that such micelles are potentially degradable into non‐toxic low molecular weight molecules, their properties and stability were proven to be pH‐dependent. This property can lead development of an “intelligent” drug carrier able to release the entrapped biologically active molecule depending on the pH values.     

Block and Graft Copolymers Made of 16‐Membered Macrolactones and l‐Alanine: A Comparative Study

Block and graft poly(macrolactone)‐poly(α‐amino acid) copolymers made of l ‐alanine and pentadecalactone or globalide respectively, are prepared. A sequential ring‐opening polymerization (ROP) copolymerization route consisting of two stages, the first devoted to the preparation of the amino‐functionalized poly(macrolactone) and the second to the amino‐initiated polymerization of l ‐alanine N‐carboxyanhydride (Ala‐NCA), is followed for the synthesis of both types of copolymers. Poly(l ‐alanine) segment lengths are accurately controlled by adjusting the macroitiator/Ala‐NCA ratio used for reaction in the second stage. Block copolymers are semicrystalline with the poly(pentadecalactone) block crystallizes well in a separate phase and the poly(α‐amino acid) block arranged in either the α‐helical or β‐sheet structure in a ratio that is depending on composition and temperature. Graft copolymers are amorphous but with the poly(α‐amino acid) side chains arranged in a more or less regular conformation. Nanoparticles with a diameter of around 300 nm and moderate positive Z‐potential can be obtained from the block copolymers by self‐assembling in water whereas graft copolymers are unable to render recognizable objects of nanometer‐dimension under similar conditions.     

Poly(ethylene glycol) analogs grafted with low molecular weight poly(ethylene imine) as non-viral gene vectors

A novel class of non-viral gene vectors consisting of low molecular weight poly(ethylene imine) (PEI) (molecular weight 800 Da) grafted onto degradable linear poly(ethylene glycol) (PEG) analogs was synthesized. First, a Michael addition reaction between poly(ethylene glycol) diacrylates (PEGDA) (molecular weight 258 Da) and d,l-dithiothreitol (DTT) was carried out to generate a linear polymer (PEG–DTT) having a terminal thiol, methacrylate and pendant hydroxyl functional groups. Five PEG–DTT analogs were synthesized by varying the molar ratio of diacrylates to thiols from 1.2:1 to 1:1.2. Then PEI (800 Da) was grafted onto the main chain of the PEG–DTTs using 1,1′-carbonyldiimidazole as the linker. The above reaction gave rise to a new class of non-viral gene vectors, (PEG–DTT)–g-PEI copolymers, which can effectively complex DNA to form nanoparticles. The molecular weights and structures of the copolymers were characterized by gel permeation chromatography, ¹H nuclear magnetic resonance and Fourier transform infrared spectroscopy. The size of the nanoparticles was <200 nm and the surface charge of the nanoparticles, expressed as the zeta potential, was between +20 and +40 mV. Cytotoxicity assays showed that the copolymers exhibited much lower cytotoxicities than high molecular weight PEI (25 kDa). Transfection was performed in cultured HeLa, HepG2, MCF-7 and COS-7 cells. The copolymers showed higher transfection efficiencies than PEI (25 kDa) tested in four cell lines. The presence of serum (up to 30%) had no inhibitory effect on the transfection efficiency. These results indicate that this new class of non-viral gene vectors may be a promising gene carrier that is worth further investigation.     

Temperature and pH Dual‐Responsive Supramolecular Polymer Hydrogels Hybridized with Functional Inorganic Nanoparticles

Supramolecular hydrogels composed of poly(ethylene glycol) (PEG) containing polymer and α‐cyclodextrins (α‐CDs) show great potential in drug delivery. Herein, PEGylated magnetic nanoparticles (MNPs) and gold nanoparticles (AuNPs) of ≈10 nm are synthesized in the presence of poly(poly(ethylene glycol) methyl ether acrylate) (PPEGMA) grafted poly(acrylic acid) copolymers (PPEGMA‐co‐PAA, P1) and PPEGMA grafted poly(2‐(dimethylamino)ethyl methacrylate) copolymers (PPEGMA‐co‐PDMAEMA, P2), respectively. The produced PEGylated NPs are hybridized into supramolecular hydrogels by mixing them with α‐CDs through inclusion complexation between PEG branches and α‐CDs. As a result, supramolecular hydrogels hybridized with inorganic MNPs and AuNPs are prepared and characterized by rheological measurements, X‐ray diffraction, and scanning electron microscopy. Both MNP and AuNP hybrid hydrogels show reversible sol–gel transition, which is stimulated by changes in temperature and pH. The nanoparticles hybridized in the hydrogels can be released gradually in the process of hydrogel disruption. These hydrogels may have potential applications in biomaterials and drug delivery.

     

Self‐Assembly and Responsive Behavior of Poly(peptide)‐Based Copolymers

Well‐defined copolymers synthesized by combining poly(ethylene glycol) (PEG) and amino acid based building blocks are investigated with regard to their helical rigidity and self‐assembly. Optical active block copolymers reported here are designed to have a pendant amino acid and polymerizable group, that is, isonitrile in order to induce helix formation and reduce the mobility of polymer chains by forming a hydrogen bond network so that a helix with reasonable rigidity can be obtained. Due to the amphiphilicity and a relatively shorter PEG as a coil, these polymers form micelles as observed under transmission electron microscopy in which copolymers PEG₁₀₈‐b‐PPIC₇₆₄ and PEG₁₀₈‐b‐PPIC₁₀₂₀ appear to be evolving into nanoparticles with a size distribution of 100–200 nm. Circular dichroism spectroscopy is employed to study the nature of the helix and its rigidity. The folding and unfolding of polymer helix as a result of the ability of a selective solvent to form/disrupt hydrogen bonds with the peptide linkage is also discussed to highlight the responsive nature of the polymer.     

Effects of Poly(N‐isopropylacrylamide) (PNIPAAm) on the Conformational Change of Poly(N 5‐hydroxyalkyl glutamine) (PHAG) in PHAG‐PNIPAAm Block Copolymer with Temperature

Diblock copolymers consisting of poly(N ⁵‐hydroxyalkylglutamine) (PHAG) and poly(N‐isopropylacrylamide) (PNIPAAm) were prepared by aminolysis with aminoalkanols of the side‐chain ester of poly(γ‐benzyl L ‐glutamate) (PBLG) as a part of PBLG‐PNIPAAm block copolymers. The molecular weight ratio of the initial PBLG to the resulting PHAG was nearly 0.35. The effect of PNIPAAm on the conformational change of PHAG in PHAG‐PNIPAAm block copolymers with temperature was investigated by circular dichroism. Poly[N ⁵‐(2‐hydroxyethyl)‐L ‐glutamine] (PHEG) and the PHEG‐PNIPAAm copolymer (GNE) stayed in a randomly coiled conformation whereas poly[N ⁵‐(3‐hydroxypropyl)‐L ‐glutamine] (PHPG), poly(N ⁵‐(4‐hydroxybutyl)‐L ‐glutamine) (PHBG), PHPG‐PNIPAAm copolymer (GNP), and PHBG‐PNIPAAm copolymer (GNB) underwent conformational transitions with temperature. The conformational change of the PHPG block in GNP copolymer occurred from an α‐helix to a random coil after the incorporation of PNIPAAm into the copolymer. The thermodynamic parameters of the thermally induced helix‐coil transition for PHBG and PHBG‐PNIPAAm in aqueous solution were calculated.     

Triblock Copolymers Based on 1,3‐Trimethylene Carbonate and Lactide as Biodegradable Thermoplastic Elastomers

Summary: Biodegradable triblock copolymers based on 1,3‐trimethylene carbonate (TMC) and different lactides (i.e. D ,L ‐lactide(DLLA), L ‐lactide (LLA), D ‐lactide (DLA)) designated as poly(DLLA‐TMC‐DLLA), poly(LLA‐TMC‐LLA) and poly(DLA‐TMC‐DLA) were prepared and their mechanical and thermal properties were compared with those of high molecular weight poly(TMC) and poly(TMC‐co‐DLLA) statistical copolymers. Triblock copolymers containing crystallizable LLA or DLA segments perform as thermoplastic elastomers (TPEs) when the poly(lactide) blocks are long enough to crystallize. In blends of poly(LLA‐TMC‐LLA) and poly(DLA‐TMC‐DLA) triblock copolymers, stereo‐complex formation between the enantiomeric poly(lactide) segments occurs as demonstrated by differential scanning calorimetry and light microscopy. These blends have good tensile properties and excellent resistance to creep under static and dynamic loading conditions.

Permanent deformation (after 2 h recovery) of compression‐molded poly(TMC) and solvent‐cast poly(LLA‐TMC‐LLA) and poly(ST‐TMC‐ST) films.     

The Synthesis of Liquid Crystalline Copolymers with Block Copolymer Grafts

The synthesis of novel copolymers consisting of a side‐group liquid crystalline backbone and poly(tetrahydrofuran)‐poly(methyl methacrylate) block copolymer grafts was realized by using cationic‐to‐free‐radical transformation reactions. Firstly, photoactive poly(tetrahydrofuran) macroinimers were prepared by cationic polymerization of tetrahydrofuran and subsequent termination with 2‐picoline N‐oxide. Secondly, the macroinimers and acrylate monomers containing different spaced cyanobiphenyl mesogenic groups were copolymerized to yield the respective graft copolymers. Eventually, these were used for indirect photochemical polymerization of methyl methacrylate by UV irradiation in the presence of anthracene as a photosensitizer leading to the final copolymers with block copolymer grafts. The liquid crystalline, semicrystalline, and amorphous blocks were micro‐phase separated in the graft copolymers.     

Triblock Copolymers Based on Sucrose Methacrylate and Methyl Methacrylate: RAFT Polymerization and Self‐Assembly

ABA and BAB triblock amphiphilic copolymers based on sucrose methacrylate and methyl methacrylate are synthesized by sequential reversible addition–fragmentation chain transfer polymerization using S,S′‐bis(R,R′‐dimethyl‐R′′‐acetic acid)‐trithiocarbonate as a chain transfer agent. The copolymers present narrow molar mass dispersity, controlled molar mass and architecture as determined by gel permeation chromatography and ¹H and ¹³C nuclear magnetic resonance. The copolymers with molar and mass fractions of poly(sucrose methacrylate) block ranging from 1 to 22 mol% and 3 to 52 wt%, respectively, and different molar masses present characteristics of a surfactant such as self‐assembly. The self‐assembly of the triblock copolymers in water, N,N‐dimethylformamide (DMF), dichloromethane, tetrahydrofuran, or benzene results mostly in vesicles as confirmed by scanning electron microscopy images and small‐angle X‐ray of the dispersions. Moreover, the copolymers present the capability to stabilize aromatic molecules (Nile Red dye) and nonpolar solvents in an aqueous phase and polar ionic molecules (methylene blue) and water in a nonpolar medium, suggesting the potential for application in drug encapsulation, environmental remediation systems, and molecular extraction in liquid–liquid immiscible systems, for example. Films prepared by casting from copolymer solutions in DMF present a lamellar structure with the lamellar thickness varying according to the copolymer molar mass.     

The Aggregation Behavior of Poly(ethylene oxide)‐Poly(methyl methacrylate) Diblock Copolymers in Organic Solvents

Poly(ethylene oxide)‐poly(methyl methacrylate) and poly(ethylene oxide)‐poly(deuteromethyl methacrylate) block copolymers have been prepared by group transfer polymerization of methyl methacrylate (MMA) and deuteromethyl methacrylate (MMA‐d₈), respectively, using macroinitiators containing poly(ethylene oxide) (PEO). Static and dynamic light scattering and surface tension measurements were used to study the aggregation behavior of PEO‐PMMA diblock copolymers in the solvents tetrahydrofuran (THF), acetone, chloroform, N,N‐dimethylformamide (DMF), 1,4‐dioxane and 2,2,2‐trifluoroethanol. The polymer chains are monomolecularly dissolved in 1,4‐dioxane, but in the other solvents, they form large aggregates. Solutions of partially deuterated and undeuterated PEO‐PMMA block copolymers in THF have been studied by small‐angle neutron scattering (SANS). Generally, large structures were found, which cannot be considered as micelles, but rather fluctuating structures. However, ¹H NMR measurements have shown that the block copolymers form polymolecular micelles in THF solution, but only when large amounts of water are present. The micelles consist of a PMMA core and a PEO shell.     

Crystalline Structure and Thermal Behavior of Water‐Soluble Copolymers with Pendant Terthiophenes

The water‐soluble copolymers having pendant terthiophene, poly(AA3T‐co‐AA), were synthesized by radical copolymerization of [(2,2′ : 5′,2′′‐terthiophen‐5‐yl)methyl acrylate] (AA3T) and acrylic acid (AA), and their molecular structures and thermal behaviors were studied. X‐ray diffraction study showed that the copolymers containing a certain amount of AA3T can form the crystals with monolayer structure, while incorporation of too many AA units into the copolymers disrupted this structure. Possible mechanism of self‐doping on heating was discussed in terms of interaction between AA3T unit with AA unit in the copolymers.     

Synthesis and characterization of non‐covalent liquid crystalline diblock copolymers

Poly(dimethylaminoethylmethacrylate)‐b‐poly(sodium methacrylate) diblocks, (polyDMAEMA‐b‐polyMA), were synthesized as precursors of liquid crystalline (LC) copolymers. These LC copolymers were prepared by proton‐transfer between a carboxylic acid‐containing mesogen (A) and the dimethylamino substituent of the polyDMAEMA block and by electrostatic interactions between the polyMA subunits and an ammonium‐containing mesogen (B). When mesogen A is complexed with DMAEMA units, a dramatic enhancement of the mesophase stability is noted. The mesogenic properties of these LC copolymers were compared to those ones of the parent LC homopolymers, in relation to the copolymer composition. The supramolecular organization of the LC diblock copolymers was studied by small‐angle X‐ray scattering (SAXS), and smectic mesophases were observed in some LC (co)polymers. For samples containing a major LC block, a smectic mesophase coexists with microphases formed by the second amorphous block. Different organizations, including a body‐centered lattice of spheres and a hexagonal array of cylinders, were observed, depending on the investigated copolymers and their composition. When the LC block is the minor component, it forms microdomains too small for a liquid crystalline order to emerge. Moreover, no supramolecular organization of these dispersed microdomains was detected by SAXS. A homogeneous smectic mesophase was observed when the two blocks are bearing liquid crystalline moieties.     

Synthesis of Block Graft Copolymer with Syndiospecific Living Polymerization of Styrene Derivatives by (Trimethyl)pentamethylcyclopentadienyltitanium/Tris(pentafluorophenyl)borane/Trioctylaluminium Catalytic System

Two kinds of syndiotactic AB type block copolymers were prepared, which were (1) poly(4‐methylstyrene)‐block‐polystyrene {Poly(4MS‐b‐S), (A: poly(4MS), B: polystyrene (S))}, (2) poly(4‐methylstyrene)‐block‐poly(styrene‐co‐3‐methylstyrene) {poly[4MS‐b‐(S‐co‐3MS)] (A: poly(4MS), B: styrene/3‐methylstyrene (3MS) copolymer)}. For the syntheses of these diblock copolymers, the living polymerization catalytic system composed of (trimethyl)pentamethylcyclopentadienyltitanium (Cp*TiMe₃) premixed with trioctylaluminium (AlOct₃), and tris(pentafluorophenyl)borane (B(C₆F₅)₃) was used at –25°C. Chlorination of the methyl groups of poly[4MS‐b‐(S‐co‐3MS)] was conducted by aqueous sodium hypochlorite (NaOCl) and phase‐transfer catalyst such as tetrabutylammonium hydrogensulfate (TBAHS). The novel tapered densely grafted diblock copolymer was synthesized with by coupling reaction of living poly(2‐vinyl pyridine)lithium (Poly(2VP)Li) with the partly chloromethylated poly[4MS‐b‐(S‐co‐3MS)].     

Thermal,Mechanical, Electrical and Morphological Characterization Studies of Poly(vinyl chloride) Blends with Various Polyitaconates and Block Copolymers of Polyitaconates/Poly(dimethyl siloxane)

Four blends were prepared by using the solvent casting method: (1) poly(mono‐butyl itaconate)/poly(vinyl chloride) PMBI/PVC; (2) poly(mono‐cyclo hexyl itaconate)/poly(vinyl chloride) PMCHI/PVC; (3) poly(mono‐butyl itaconate)‐poly(dimethyl siloxane)‐poly(mono‐butyl itaconate)/poly(vinyl chloride) PMBI‐PDMS‐PMBI/PVC; and (4) poly(mono‐cyclo hexyl itaconate)‐poly(dimethyl siloxane)‐poly(mono‐cyclo hexyl itaconate) PMCHI‐PDMS‐PMCHI/PVC. These blends were characterized by differential scanning calorimetry (DSC), stress‐strain tests (TENSILON), dielectric thermal analysis (DETA), impedance spectroscopy (IS) and scanning electron microscopy (SEM) analyses. The results showed that the addition of about 1% poly(mono itaconates), or about 1–3% block copolymers containing PDMS blocks have clearly a plasticizing effect on PVC. All characterization methods confirm this conclusion. The addition of higher amounts of homo‐ and block copolymers causes other variations, as a results of several overlapping and synergetic effects.     

Synthesis and in vitro drug release behavior of amphiphilic triblock copolymer nanoparticles based on poly (ethylene glycol) and polycaprolactone

Novel BAB type amphiphilic triblock copolymers consisting of poly (ethylene glycol) (PEG) (B) as hydrophilic segment and poly (epsilon-caprolactone) (PCL) (A) as hydrophobic block were prepared by coupling reaction using L-lysine methyl ester diisocyanate (LDI) as the chain extender. The triblock copolymers obtained were characterized by FT-IR, 1H NMR, GPC, and DSC. Core-shell type nanoparticles were prepared by nanoprecipitation method and below 100 nm nanoparticles were obtained due to their specific structure. Transmission electron microscopy image demonstrated that these nanoparticles were spherical in shape. Stability of the nanoparticles in biological media was evaluated. Poorly water-soluble anticancer drug 4'-demethyl-epipodophyllotoxin (DMEP) was chosen for controlled drug release because it was easily encapsulated into polymeric nanoparticles via hydrophobic interaction. In vitro release behavior of DMEP from polymeric nanoparticles was investigated, the results showed that the drug release rate can be modulated by the variation of the copolymer composition.     

Tunable Morphologies From Bulk Self‐Assemblies of Poly(acryloxypropyl triethoxysilane)‐b‐poly(styrene)‐b‐poly(acryloxypropyl triethoxysilane) Triblock Copolymers

Reactive poly(acryloxypropyl triethoxysilane)‐b‐poly(styrene)‐b‐poly(acryloxypropyl triethoxysilane) (PAPTES‐b‐PS‐b‐PAPTES) triblock copolymers are prepared through nitroxide‐mediated polymerization (NMP). The bulk morphologies formed by this class of copolymers cast into films are examined by small‐angle X‐ray scattering (SAXS) and transmission electron microscopy (TEM). The films morphology can be tuned from spherical structures to lamellar structures by increasing the volume fraction of PS in the copolymer. Thermal annealing at temperatures above 100 °C provides sufficient PS mobility to improve ordering.     

Gelation Behavior of Bioabsorbable Hydrogels Consisting of Enantiomeric Mixtures of A–B–A Tri‐block Copolymers of Polylactides (A) and Poly(ethylene glycol) (B)

A–B–A tri‐block copolymers of poly(L ‐lactide) (PLLA: A) and poly(ethylene glycol) (PEG: B) and those of poly(D ‐lactide) (PDLA: A) and PEG (B) were prepared and suspended in saline. Mixing suspensions consisting of the enantiomeric copolymers with identical block compositions induced a temperature‐dependent sol‐to‐gel transition. It was found that the composition window of the copolymers that allowed the spontaneous sol–gel transition around body temperature was considerably narrow, being affected by how easily the PLLA and PDLA blocks of the copolymers can form the stereocomplex in the mixed suspensions. The gelation rate and gel strength also depended on the copolymer composition and concentration at a constant gelation temperature of 37 °C.