Thermoresponsive core-shell-corona micelles of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene

Core-shell-corona micelles with a thermoresponsive shell self-assembled by triblock copolymer of poly(ethyleneglycol)-b-poly(N-isopropylacrylamide)-b-polystyrene (PEG₄₅-b-PNIPAM₁₆₈-b-PS₄₆) are studied by ¹H NMR, light scattering and atomic force microscopy. The thermoresponsive triblock copolymer, which has a relatively short hydrophobic PS block, can disperse in water at room temperature to form core-shell-corona micelles with the hydrophobic PS block as core, the thermoresponsive PNIPAM block as shell and the hydrophilic PEG block as corona. At temperature above lower critical solution temperature (LCST) of the PNIPAM block, the PNIPAM chains gradually collapse on the PS core to shrink the size and change the structure of the resultant core-shell-corona micelles with temperature increasing. It is found that there possibly exists an interface between the PNIPAM shell and PEG corona of the core-shell-corona micelles at temperature above LCST of the PNIPAM block.     

Synthesis and characterization of poly(ethylene glycol)-b-poly (l-lactide)-b-poly(l-glutamic acid) triblock copolymer

A biodegradable amphiphilic triblock copolymer of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-glutamic acid) (PEG-b-PLLA-b-PLGA) was obtained by catalytic hydrogenation of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(γ-benzyl-l-glutamic acid) (PEG-b-PLLA-b-PBLGA) synthesized by the ring-opening polymerization (ROP) of N-carboxyanhydride of γ-benzyl-l-glutamate (BLG-NCA) with amino-terminated MPEG-b-PLLA-NH₂ as a macroinitiator. MPEG-b-PLLA-NH₂ converted from MPEG-b-PLLA-OH first reacted with tert-Butoxycarbonyl-l-phenylalanine (Phe-^NBOC) and dicyclohexylcarbodiimide (DCC) and then deprotected the tert-butoxycarbonyl group. MPEG-b-PLLA-OH was prepared by ROP of l-lactide with monomethoxy poly(ethylene glycol) in the presence of stannous octoate. The triblock copolymer and its diblock precursors were characterized by ¹H NMR, FTIR, GPC and DSA (drop shape analysis) measurements. The lengths of each block polymers could be tailored by molecular design and the ratios of feeding monomers. The triblock polymer PEG-b-PLLA-b-PLGA containing carboxyl groups showed obviously improved hydrophilic properties and could be a good potential candidate as a drug delivery carrier.     

The influence of hydrophobic substitution on self-association of poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers in aqueous media

A series of amphiphilic poly(ethylene oxide)-b-poly(n-alkyl glycidyl carbamate)s-b-poly(ethylene oxide) triblock copolymers were synthesized by reaction between poly(ethylene oxide)-b-polyglycidol-b-poly(ethylene oxide) precursor copolymer and four n-alkyl isocyanates: ethyl, propyl, butyl and pentyl. After dissolution in water at room temperature the copolymers spontaneously form micelles. The critical micellization concentrations were determined by UV-VIS spectroscopy. The dimensions of the micelles, the aggregation numbers, and in some cases the micellar shape were determined by dynamic and static light scattering in a relatively broad temperature range. Special attention has been paid to the influence of the number of the carbon atoms in the alkyl chains, and respectively, the relative hydrophobicity of the middle block upon the self-association process. Clouding transition was observed for all of the copolymers, the clouding point being dependent upon the length of the alkyl chain.     

Physical properties of poly(cyclohexyl methacrylate)-b-poly(iso-butyl acrylate)-b-poly(cyclohexyl methacrylate) triblock copolymers synthesized by controlled radical polymerization

The microphase segregation of different poly(cyclohexyl methacrylate)-b-poly(iso-butyl acrylate)-b-poly(cyclohexyl methacrylate), PCH-b-PiBA-b-PCH, triblock copolymers obtained by atom transfer radical polymerization has been evaluated by dynamic mechanical thermal analysis through location of the two relaxations ascribed to cooperative motions of each block. Additionally, other secondary relaxations have been found, whose characteristics are also dependent on molecular weight of outer and rigid segments. The length of these hard blocks influences significantly the stiffness and microhardness found in these triblock copolymers. These two mechanical parameters increase as molecular weight of poly(cyclohexyl methacrylate) does. The morphological aspects have been examined by small angle X-ray scattering and atomic force microscopy.     

The effect of polystyrene-block-poly(4-vinylpyridine) prepared by a RAFT method in the dispersion polymerization of MMA

The dispersion polymerization of methyl methacrylate (MMA) has been carried out using polystyrene-block-poly(4-vinylpyridine) copolymer [P(S-b-4VP)], which was prepared by a reversible addition-fragmentation chain transfer (RAFT) method, as a steric stabilizer in an alcohol media. The stable polymer particles were obtained when the block copolymer concentrations increased from 1 to 10 wt% relative to the monomer and the average particle sizes decreased from 5.3 to 3.4 μm with the increasing concentration of the block copolymer. In particular, the incorporation of 2 wt% polystyrene-block-poly(4-vinylpyridine) produced 4.3 μm of monodisperse PMMA particles with 2.14% of C_v. Thus, the P(S-b-4VP) block copolymer prepared by the RAFT method is working not only as a steric stabilizer, but also in providing monodisperse micron-sized PMMA particles.     

Synthesis and micellization of thermo- and pH-responsive block copolymer of poly(N-isopropylacrylamide)-block-poly(4-vinylpyridine)

A novel double-hydrophilic block copolymer poly(N-isopropylacrylamide)-block-poly(4-vinylpyridine) (PNIPAM-b-P4VP) with low polydispersity which could respond to both temperature and pH stimuli in aqueous solution was synthesized by atom transfer radical polymerization. Micellization of the copolymer in aqueous solution was characterized by dynamic and static laser scattering, ¹H NMR and transmission electron microscopy. In aqueous solution, the copolymer existed as unimer at pH 2.8 at 25 °C. When the temperature was raised to 50 °C at pH 2.8, the copolymer associated into spherical core-shell micelles with the PNIPAM block forming the core and the P4VP block forming the shell. On the other hand, when pH was increased from 2.8 to 6.5 at 25 °C, the copolymer associated into spherical core-shell micelles with the core formed by the P4VP block and the shell formed by the PNIPAM block. The process was reversible. The critical aggregation temperature of the block copolymer is 36 °C, and the critical aggregation pH value is 4.7.     

A biodegradable triblock copolymer poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-lysine): Synthesis,self-assembly,and RGD peptide modification

A novel biodegradable triblock copolymer poly(ethylene glycol)-b-poly(l-lactide)-b-poly(l-lysine) (PEG–PLA–PLL) was synthesized by acidolysis of poly(ethylene glycol)-b-poly(l-lactide)-b-poly(ɛ-benzyloxycarbonyl-l-lysine) (PEG–PLA–PZLL) obtained by the ring-opening polymerization (ROP) of ɛ-benzyloxycarbonyl-l-lysine N-carboxyanhydride (ZLys NCA) with amino-terminated PEG–PLA–NH₂ as a macroinitiator, and the pendant amino groups of the lysine residues were modified with a peptide known to modulate cellular functions, Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY, abbreviated as RGD) in the presence of 1,1′-carbonyldiimidazole (CDI). The structures of PEG–PLA–PLL/RGD and its precursors were confirmed by ¹H NMR, FT-IR, amino acid analysis and XPS analysis. The cell adhesion and cell spread on the PEG–PLA–PLL/RGD film were enhanced compared to those on pure PLA film. Therefore, the novel RGD-grafted triblock copolymer is promising for cell or tissue engineering applications. Both copolymers PEG–PLA–PZLL and PEG–PLA–PLL showed an amphiphilic nature and could self-assemble into micelles of homogeneous spherical morphology. The micelles were determined by fluorescence technique, dynamic light scattering (DLS), and field emission scanning electron microscopy (ESEM) and could be expected to find application in drug and gene delivery systems.     

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

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

Transition behavior and ionic conductivity of lithium perchlorate-doped polystyrene-b-poly(2-vinylpyridine)

We report the transition behavior and the ionic conductivity of ion-doped amorphous block copolymer, based on two compositionally different polystyrene-block-poly(2-vinylpyridine) copolymers (PS-b-P2VPs) that can self-assemble into nanostructures, where P2VP block is ionophilic to lithium perchlorate (LiClO₄). The transition temperatures of LiClO₄-doped PS-b-P2VP, like the order-to-disorder transition (T_ODT), were measured by small-angle X-ray scattering (SAXS) and depolarized light scattering (DPLS). The selective ionic coordination to the nitrogen units of P2VP block leads to the increase of the repulsive interactions between two block components from weak- to strong-segregation regime with increasing amount of LiClO₄, which results subsequently in the increased T_ODT. However, for a compositionally asymmetric PS-b-P2VP under lamellar morphology, the ionic conductivity by the addition of LiClO₄ was remarkably increased at higher temperatures, representing that the effective ionic coordination at the greater volume fraction of P2VP block component improves the ionic conductivity as the temperature approaches to a rubbery phase.     

Exfoliation of organoclay nanocomposites based on polystyrene-block-polyisoprene-block-poly(2-vinylpyridine) copolymer: Solution blending versus melt blending

Exfoliated nanocomposites based on polystyrene-block-polyisoprene-block-poly(2-vinylpyridine) (SI2VP triblock) copolymer were prepared by solution blending and melt blending. Their dispersion characteristics were investigated using transmission electron microscopy, X-ray diffraction, and small-angle X-ray scattering (SAXS). For the study, SI2VP triblock copolymers with varying amounts of poly(2-vinylpyridine) (P2VP) block (3, 5, and 13 wt%) and different molecular weights were synthesized by sequential anionic polymerization. In the preparation of nanocomposites, four different commercial organoclays, treated with a surfactant having quaternary ammonium salt, were employed. It was found from SAXS that the microdomain structure of an SI2VP triblock copolymer having 13 wt% P2VP block (SI2VP-13) transformed from core-shell cylinders into lamellae when it was mixed with an organoclay. It was found further that the solution-blended nanocomposites based on a homogeneous SI2VP triblock copolymer having 5 wt% P2VP block (SI2VP-5) gave rise to an exfoliated morphology, irrespective of the differences in chemical structure of the surfactant residing at the surface of the organoclays, which is attributable to the presence of ion-dipole interactions between the positively charged N⁺ ion in the surfactant residing at the surface of the organoclay and the pyridine rings in the P2VP block of SI2VP-5 and SI2VP-13, respectively. Both solution- and melt-blended nanocomposites based on microphase-separated SI2VP-13 having an order-disorder transition temperature (T_ODT) of approximately 210 °C also gave rise to exfoliated morphology. However, melt-blended nanocomposite based on a high-molecular-weight SI2VP triblock copolymer having a very high T_ODT (estimated to be about 360 °C), which was much higher than the melt blending temperature employed (200 °C), gave rise to very poor dispersion of the aggregates of organoclay. It is concluded that the T_ODT of a block copolymer plays a significant role in determining the dispersion characteristics of organoclay nanocomposites prepared by melt blending.     

Control of the confined and unconfined crystallization in glassy-crystalline poly(vinylcyclohexane)-b-poly(ethylene)-b-poly-(vinylcyclohexane) triblock copolymer in solution

The influence of the solvent evaporation rate on the crystallization of the poly(vinylcyclohexane)-b-poly(ethylene)-b-poly(vinylcyclohexane) (PVCH-PE-PVCH) triblock copolymer with the high T_g of PVCH segment in chloroform was investigated. The competition between the crystallization of PE block and the vitrification of PVCH in the triblock copolymer was controlled through changing the solvent evaporation rate in the solution system at different temperatures (T_e). It was found that the melting temperature (T_m) of PVCH-PE-PVCH samples increased with increasing the T_e when the T_e was lower than the solvent boiling point (bp), depending on the crystalline temperatures. However, when T_e was just a little above the solvent bp, two melting peaks, which corresponding to the fusion of the confined and unconfined crystals, respectively, were observed on the DSC curves of the samples. As T_e increased to be higher temperature, only one lower melting peak, which corresponding to the fusion of the confined crystals, existed for each samples. It was also found that the crystallinity (X_c) of the samples decreased gradually when T_e was lower than the solvent bp, and then decreased suddenly when T_e was just a little above the solvent bp, finally reached a plateau (about 13.5%) at higher T_e. The changes in X_c of the samples depend on the evaporating time in the solution. The results should be related to the competition between the crystallization of PE block in solvent and the vitrification of PVCH block with the solvent evaporation. Furthermore, the competition was controlled through changing the solvent evaporation rate. The confined and unconfined crystallization of the samples could be freely adjusted.     

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

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

Double-responsive core-shell-corona micelles from self-assembly of diblock copolymer of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-isopropylacrylamide)

Self-assembly of poly(t-butyl acrylate-co-acrylic acid)-b-poly(N-isopropylacrylamide) [P(tBA-co-AA)-b-PNIPAM], which was obtained from part hydrolysis of PtBA-b-PNIPAM synthesized by sequential atom transfer radical polymerization (ATRP) was studied. Thermo- and pH-responsive core-shell-corona (CSC) micelles with different structures were formed from (PtBA-co-PAA)-b-PNIPAM in aqueous solution. At pH 5.8 and 25 °C, the block copolymer self-assembled into spherical core-shell micelles with hydrophobic PtBA segments as the core, hydrophilic PAA/PNIPAM segments as the mixed shell. Increasing temperatures, core-shell micelles converted into CSC micelles with PtBA as the core, collapsed PNIPAM as the shell and soluble PAA as the corona. Moreover, decreasing pH at 25 °C, PAA chains collapsed onto the core resulting in CSC micelles with PtBA as the core, PAA as the shell and PNIPAM as the corona.     

Synthesis of poly(ethylene oxide)-block-poly(methyl methacrylate)-block-polystyrene triblock copolymers by two-step atom transfer radical polymerization

The synthesis of ABC triblock copolymer poly(ethylene oxide)-block-poly(methyl methacrylate)-block-polystyrene (PEO-b-PMMA-b-PS) via atom transfer radical polymerization (ATRP) is reported. First, a PEO-Br macroinitiator was synthesized by esterification of PEO with 2-bromoisobutyryl bromide, which was subsequently used in the preparation of halo-terminated poly(ethylene oxide)-block-poly(methyl methacrylate) (PEO-b-PMMA) diblock copolymers under ATRP conditions. Then PEO-b-PMMA-b-PS triblock copolymer was synthesized by ATRP of styrene using PEO-b-PMMA as a macroinitiator. The structures and molecular characteristics of the PEO-b-PMMA-b-PS triblock copolymers were studied by FT-IR, GPC and ¹H NMR.     

Shell-core-corona aggregates formed from poly(styrene)-poly(4-vinylpyridine) block copolymer induced by added homopolymer via interpolymer hydrogen-bonding

The solution behavior of poly(styrene)-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer with added poly(4,4′-oxydiphenylenepyromellitamic acid) (POAA) homopolymer in DMF is studied by dynamic light scattering (DLS), nuclear magnetic resonance (NMR), and transmission electron microscopy (TEM). It is found that coaggregation takes place when mixing PS-b-P4VP block copolymer and POAA homopolymer in DMF due to the strong interpolymer hydrogen-bonding between POAA chains and P4VP blocks. The coaggregation is a diffusion-controlled process and the complexation-induced aggregates are very stable. NMR measurements demonstrate that the resultant aggregates are much more swollen compared with typical amphiphilic block copolymer core-shell micelles. DLS measurements with Eu³⁺ as a probe combined with TEM observation, are employed to study the structure of the aggregates. Results reveal that the formed aggregates are core-shell spheres with the P4VP/POAA complexes as core and the PS blocks as shell when the weight ratio of POAA to PS-b-P4VP is lower. However, a core-shell-corona structure forms with a thin layer of POAA chains adsorbed on the initial core-shell aggregates with increasing weight content of POAA to 60%. Finally, possible mechanisms of the structural transitions are proposed.     

Synthesis and characterization of dual stimuli-responsive block copolymers based on poly(N-isopropylacrylamide)-b-poly(pseudoamino acid)

The current study synthesized amphiphilic thermal/pH-sensitive block copolymers PNiPAAm-b-PHpr by condensation polymerization of trans-4-hydroxy-l-proline (Hpr) initiated from hydroxy-terminated poly(N-isopropylacrylamide) (PNiPAAm) as the macroinitiator in the presence of the catalyst, SnOct₂. ¹H NMR, FTIR, and gel permeation chromatography (GPC) characterized these copolymers. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. The LCST values depended on the polymer composition and the media. With critical micelle concentrations (CMCs) in the range of 1.23-3.73 mg L⁻¹, the block copolymers formed micelles in the aqueous phase owing to their amphiphilic characteristics. Increased hydrophobic segment length or decreased hydrophilic segment length in an amphiphilic diblock copolymer produced lower CMC values. The current work proved the core-shell structure of micelles by ¹H NMR analyses of the micelles in D₂O. Transmission electron microscopy analyzed micelle morphology, showing a spherical core-shell structure. The micelles had an average size in the range of 170˜210 nm (blank), and 195˜280 nm (with drug). Observations showed high drug entrapment efficiency and drug-loading content for the drug micelles.     

Micellization and sol-gel transition of novel thermo- and pH-responsive ABC triblock copolymer synthesized by RAFT

A well-defined thermo- and pH-responsive ABC-type triblock copolymer monomethoxy poly(ethylene glycol)-b-poly(2-(2-methoxyethoxy) ethyl methacrylate-co-N-hydroxymethyl acrylamide)-b-poly(2-(diethylamino) ethyl methacrylate), mPEG-b-P(MEO₂MA-co-HMAM)-b-PDEAEMA, was synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT). The ABC-type triblock copolymer was endowed thermo- and pH-responsive, corresponding to the thermosensitive properties of P(MEO₂MA-co-HMAM) and pH-responsive properties PDEAEMA segments, respectively. The thermo- and pH-responsive properties of copolymer aqueous solutions were studied by UV transmittance measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM). The results showed that the N-hydroxymethyl acrylamide (HMAM) content in triblock copolymer affected the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution. The copolymer self-assembled into core-shell micelles, with the thermoresponsive P(MEO₂MA-co-HMAM) block and the hydrophilic PEG block as the shell, the hydrophobic PDEAEMA block as the core, in alkaline solution at room temperature. While in acidic media, when the temperature above the lower critical solution temperature (LCST) of the triblock copolymer aqueous solution, the copolymer self-assembled into P(MEO₂MA-co-HMAM)-core micelles with mixed hydrophilic PEG and pH-responsive PDEAEMA coronas. Sol-gel transition temperature (T_sol-gel) for the triblock copolymer determined by vial inversion test further indicated that it is dependent on the concentration of the triblock copolymers and solution pH. Copolymer hydrogel loaded with bovine serum albumin (BSA) were used for the sustained release study. The results indicated that the hydrogel was a promising candidate for controlling protein drug delivery.     

Vesicle formation of polystyrene-block-poly (ethylene oxide) block copolymers induced by supercritical CO2 treatment

A novel route for a preparation of polystyrene-block-poly(ethylene oxide) (PS-b-PEO) block copolymer vesicles induced by supercritical carbon dioxide (scCO₂) is demonstrated. When PS-b-PEO block copolymer solutions in tetrahydrofuran (THF) are treated with scCO₂ at 70 °C for different times, PS-b-PEO copolymers first assemble into aggregated spheres; then aggregated spheres change into large compound micelles and finally evolve into vesicles. The possible formation mechanism of the vesicles is discussed.     

Dissipative particle dynamics study on the multicompartment micelles self-assembled from the mixture of diblock copolymer poly(ethyl ethylene)-block-poly(ethylene oxide) and homopolymer poly(propylene oxide) in aqueous solution

Dissipative particle dynamics (DPD) method is applied to model the self-assembly of diblock copolymer poly(ethyl ethylene)-block-poly(ethylene oxide) (PEE-b-PEO) and homopolymer poly(propylene oxide) (PPO) in aqueous solution. In this study, several segments are coarse-grained into a single simulation bead based on the experimental density. For the self-assembly of pure diblock copolymer PEE-b-PEO in dilute solution, the DPD simulation results are in good agreement with experimental data of micelle morphologies and sizes. The chain lengths of the block copolymers and the volume ratios between PPO and PEE-b-PEO are varied to find the conditions of forming multicompartment micelles. The micelles with core-shell-corona structure and the micelles with two compartments are both formed from the mixture of PEE-b-PEO and PPO in aqueous solution.