Biocompatible poly(ethylene glycol)‐poly(γ‐cholesterol‐L‐glutamate) copolymers: Synthesis,characterization, and in vitro studies

A novel amphiphilic poly(ethylene glycol)‐block‐poly(γ‐cholesterol‐L ‐glutamate) (mPEG–PCHLG) diblock copolymer has been synthesized. The mPEG–PCHLG copolymer has good biocompatibility and low toxicity. The mPEG–PCHLG copolymers could aggregate into nanoparticles with PCHLG blocks as the hydrophobic core and PEG blocks as the hydrophilic shell through emulsion solvent evaporation method. The copolymers were characterized by nuclear magnetic resonance spectroscopy, mass spectrum, Fourier transform infrared spectroscopy, and gel permeation chromatography. The particle sizes, size distributions, and zeta potentials of nanoparticles can also be determined by dynamic light scattering and transmission electron microscopy. This work provides a new and facile approach to prepare amphiphilic block copolymer nanoparticles with controllable performances. This novel copolymer may have potential applications in drug delivery and bioimaging applications.© 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Thermosensitive behavior of poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) double hydrophilic block copolymers

The poly(ethylene glycol)/poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (PEG/PDMAEMA) double hydrophilic block copolymers were synthesized by atom transfer radical polymerization using mPEG‐Br or Br‐PEG‐Br as macroinitiators. The narrow molecular weight distribution of PEG/PDMAEMA block copolymers was identified by gel permeation chromatography results. The thermosensitivity of PEG/PDMAEMA block copolymers in aqueous solution was revealed to depend significantly on pH, ionic strength, chain structure, and concentration of the block copolymers. By optimizing these factors, the cloud point temperature of PEG/PDMAEMA block copolymers can be limited within body temperature range (30–37 °C), which suggests that PEG/PDMAEMA block copolymers could be a good candidate for drug delivery systems. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 503–508, 2010     

Phase‐transition characteristics of amphiphilic poly(2‐ethyl‐2‐oxazoline)/poly(ε‐caprolactone) block copolymers in aqueous solutions

Amphiphilic diblock and triblock copolymers of various block compositions based on hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOz) and hydrophobic poly(ε‐caprolactone) were synthesized. The micelle formation of these block copolymers in aqueous media was confirmed by a fluorescence technique and dynamic light scattering. The critical micelle concentrations ranged from 35.5 to 4.6 mg/L for diblock copolymers and 4.7 to 9.0 mg/L for triblock copolymers, depending on the block composition. The phase‐transition behaviors of the block copolymers in concentrated aqueous solutions were investigated. When the temperature was increased, aqueous solutions of diblock and triblock copolymers exhibited gel–sol transition and precipitation, both of which were thermally reversible. The gel–sol transition‐ and precipitation temperatures were manipulated by adjustment of the block composition. As the hydrophobic portion of block copolymers became higher, a larger gel region was generated. In the presence of sodium chloride, the phase transitions were shifted to a lower temperature level. Sodium thiocyanate displaced the gel region and precipitation temperatures to a higher temperature level. The low molecular weight saccharides, such as glucose and maltose, contributed to the shift of phase‐transition temperatures to a lower temperature level, where glucose was more effective than maltose in lowering the gel–sol transition temperatures. The malonic acid that formed hydrogen bonds with the PEtOz shell of micelles was effective in lowering phase‐transition temperatures to 1.0M, above which concentration the block copolymer solutions formed complex precipitates. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2400–2408, 2000     

Synthesis of end‐functionalized AB copolymers. II. Synthesis and characterization of carboxyl‐terminated poly(ethylene glycol)–poly(amino acid) block copolymers

AB block copolymers composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(amino acid) with a carboxyl group at the end of PEG were synthesized with α‐carboxylic sodium‐ω‐amino‐PEG as a macroinitiator for the ring‐opening polymerization of N‐carboxy anhydride. Characterizations by ¹H NMR, IR, and gel permeation chromatography were carried out to confirm that the diblock copolymers were formed. In aqueous media this copolymer formed self‐associated polymer micelles that have a carboxyl group on the surface. The carboxyl groups located at the outer shell of the polymeric micelle were expected to combine with ligands to target specific cell populations. The diameter of the polymer micelles was in the range of 30–80 nm. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3527–3536, 2004     

Synthesis and characterization of amphiphilic block copolymers with allyl side‐groups

The synthesis of a new cyclic carbonate monomer containing an allyl group was reported and its biodegradable amphiphilic block copolymer, poly(ethylene glycol)‐block‐poly(L ‐lactide‐co‐5‐methyl‐5‐allyloxycarbonyl‐propylene carbonate) [PEG‐b‐P(LA‐co‐MAC)] was synthesized by ring‐opening polymerization (ROP) of L ‐lactide (LA) and 5‐methyl‐5‐allyloxycarbonyl‐1,3‐dioxan‐2‐one (MAC) in the presence of poly (ethylene glycol) as a macroinitiator, with diethyl zinc as a catalyst. ¹³C NMR and ¹H NMR were used for microstructure identification of the copolymers. The copolymer could form micelles in aqueous solution. The core of the micelles is built of the hydrophobic P(LA‐co‐MAC) chains, whereas the shell is set up by the hydrophilic PEG blocks. The micelles exhibited a homogeneous spherical morphology and unimodal size distribution. By using the cyclic carbonate monomer containing allyl side‐groups, crosslinking of the PEG‐b‐P(LA‐co‐MAC) inner core was possible. The adhesion and spreading of ECV‐304 cells on the copolymer were better than that on PLA films. Therefore, this biodegradable amphiphilic block copolymer is expected to be used as a biomaterial for drug delivery and tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5518–5528, 2007     

Spontaneous formation of narrowly‐distributed self‐assembly from polyamidoamine dendron‐poly(L‐lysine) block copolymers through helix‐coil transition of poly(L‐lysine) block

The self‐assembly of head‐tail type block copolymers composed of polyamidoamine dendron head block and poly(L ‐lysine) (PLL) tail block was studied using a light scattering technique and transmission electron microscopy. A PLL tail block in a head‐tail type block copolymer exhibits a coil‐to‐helix transition as a result of the change in solvent quality from water to methanol. When the PLL tail block takes a helical conformation in high methanol content, the resulting head‐tail type block copolymer has a defined three‐dimensional structure like that of a protein molecule. Self‐assemblies of such block copolymers having a totally fixed molecular shape spontaneously form polymersome‐like self‐assemblies with an extremely narrow size distribution through converging to a thermodynamically stable assembling state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1217–1223, 2009     

Solubility behavior of amphiphilic block and random copolymers based on 2‐ethyl‐2‐oxazoline and 2‐nonyl‐2‐oxazoline in binary water–ethanol mixtures

The solution properties of random and block copolymers based on 2‐ethyl‐2‐oxazoline (EtOx) and 2‐nonyl‐2‐oxazoline (NonOx) were investigated in binary solvent mixtures ranging from pure water to pure ethanol. The solubility phase diagrams for the random and block copolymers revealed solubility (after heating), insolubility, dispersions, micellization as well as lower critical solution temperature (LCST) and upper critical solution temperature behavior. The random and block copolymers containing over 60 mol % pNonOx were found to be solubilized in ethanol upon heating, whereas the dissolution temperature of the block copolymers was found to be much higher than for the random copolymers due to the higher extent of crystallinity. Furthermore, the block copolymer containing 10 mol % pNonOx exhibited a LCST in aqueous solution at 68.7 °C, whereas the LCST for the random copolymer was found to be only 20.8 °C based on the formation of hydrophobic microdomains in the block copolymer. The random copolymer displayed a small increase in LCST up to a solvent mixture of 9 wt % EtOH, whereas further increase of ethanol led to a decrease in LCST, which is probably due to the “water‐breaking” effect causing an increased attraction between ethanol and the hydrophobic part of the copolymer. In addition, the EtOx‐NonOx block copolymers revealed the formation of micelles and dynamic light scattering demonstrated that the micellar size is increasing with increasing the ethanol content due to the enhanced solubility of EtOx. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 515–522, 2009     

Direct synthesis of amphiphilic block copolymers from glycidyl methacrylate and poly(ethylene glycol) by cationic ring‐opening polymerization and supramolecular self‐assembly thereof

Amphiphilic block copolymers composed of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic poly(glycidyl methacrylate) (PGMA) block were synthesized through cationic ring‐opening polymerization with PEG as the precursor. The model reactions indicated that the reactivity of the epoxy groups was higher than that of the double bonds in the bifunctional monomer glycidyl methacrylate (GMA) under the cationic polymerization conditions. Through the control of the reaction time in the synthesis of block copolymer PEG‐b‐PGMA, a linear GMA block was obtained through the ring‐opening polymerization of epoxy groups, whereas the double bond in GMA remained unreacted. The results showed that the molecular weight of the PEG precursor had little influence on the grafting of GMA, and the PGMA blocks almost kept the same length, despite the difference of the PEG blocks. In addition, the PGMA blocks only consisted of several GMA units. The obtained amphiphilic PEG‐b‐PGMA block copolymers could form polymeric core–shell micelles by direct molecular self‐assembly in water. The crosslinking of the PGMA core of the PEG‐b‐PGMA micelles, induced by ultraviolet radiation and heat instead of crosslinking agents, greatly increased the stability of the micelles. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2038–2047, 2005     

Micelle formation and sol–gel transition behavior of comb‐like amphiphilic poly((PLGA‐b‐PEG)MA) copolymers

Comb‐like amphiphilic poly(poly((lactic acid‐co‐glycolic acid)‐block‐poly(ethylene glycol)) methacrylate (poly((PLGA‐b‐PEG)MA)) copolymers were synthesized by radical polymerization. (PLGA‐b‐PEG)MA macromonomer was prepared by ring‐opening bulk polymerization of DL ‐lactide and glycolide using purified poly(ethylene glycol) monomethacrylate (PEGMA) as an initiator. (PLGA‐b‐PEG)MA macromonomer was copolymerized with PEGMA and/or acrylic acid (AA) by radical polymerization to produce comb‐like amphiphilic block copolymers. The molecular weight and chemical structure were investigated by GPC and ¹H NMR. Poly((PLGA‐b‐PEG)MA) copolymer aqueous solutions showed gel–sol transition behavior with increasing temperature, and gel‐to‐sol transition temperature decreased as the compositions of the hydrophilic PEGMA and AA increased. The gel‐to‐sol transition temperature of the terpolymers of the poly((PLGA‐b‐PEG)MA‐co‐PEGMA‐co‐AA) also decreased when the pH was increased. The effective micelle diameter obtained from dynamic light scattering increased with increasing temperature and with increasing pH. The critical micelle concentration increased as the composition of the hydrophilic monomer component, PEGMA and AA, were increased. The spherical shape of the hyperbranched polymers in aqueous environment was observed by atomic force microscopy. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1954–1963, 2008     

Synthesis and self‐assembly of thermosensitive double‐hydrophilic poly(N‐vinylcaprolactam)‐b‐poly(N‐vinyl‐2‐pyrrolidone) diblock copolymers

We report on novel diblock copolymers of poly(N‐vinylcaprolactam) (PVCL) and poly(N‐vinyl‐2‐pyrrolidone) (PVPON) (PVCL‐b‐PVPON) with well‐defined block lengths synthesized by the MADIX/reversible addition‐fragmentation chain transfer (RAFT) process. We show that the lower critical solution temperatures (LCST) of the block copolymers are controllable over the length of PVCL and PVPON segments. All of the diblock copolymers dissolve molecularly in aqueous solutions when the temperature is below the LCST and form spherical micellar or vesicular morphologies when temperature is raised above the LCST. The size of the self‐assembled structures is controlled by the molar ratio of PVCL and PVPON segments. The synthesized homopolymers and diblock copolymers are demonstrated to be nontoxic at 0.1–1 mg mL^?1 concentrations when incubated with HeLa and HEK293 cancer cells for various incubation times and have potential as nanovehicles for drug delivery. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2725–2737     

PEG‐b‐PtBA‐b‐PHEMA well‐defined amphiphilic triblock copolymer: Synthesis,self‐assembly,and application in drug delivery

A series of well‐defined amphiphilic triblock copolymers, poly(ethylene glycol)‐b‐poly(tert‐butyl acrylate)‐b‐poly(2‐hydroxyethyl methacrylate) (PEG‐b‐PtBA‐b‐PHEMA), were synthesized via successive atom transfer radical polymerization (ATRP). ATRP of tBA was first initiated by PEG‐Br macroinitiator using CuBr/N,N,N′,N″,N′″‐pentamethyldiethylenetriamine as catalytic system to give PEG‐b‐PtBA diblock copolymer. This copolymer was then used as macroinitiator to initiate ATRP of HEMA, which afforded the target triblock copolymer, PEG‐b‐PtBA‐b‐PHEMA. The critical micelle concentrations of obtained amphiphilic triblock copolymers were determined by fluorescence spectroscopy using N‐phenyl‐1‐naphthylamine as probe. The morphology and size of formed aggregates were investigated by transmission electron microscopy and dynamic light scattering, respectively. Finally, an acid‐sensitive PEG‐b‐PtBA‐b‐P(HEMA‐CAD) prodrug via cis‐aconityl linkage between doxorubicin and hydroxyls of triblock copolymers with a high drug loading content up to 38%, was prepared to preliminarily explore the application of triblock copolymer in drug delivery. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and aggregation of poly(valine)‐poly (ethylene glycol) block copolymers

The solubility nature of many medicines presents a challenge for successful delivery of these drugs to the body. Polymeric carriers are potentially viable as vessels for both the protection and transport of these medicinal substances. In an effort to generate polymeric materials for this desired application, A‐B‐A triblock copolymers have been synthesized with a central block composed of hydrophilic poly (ethylene glycol) (PEG) and flanking hydrophobic sequences composed of five valine units terminated with end groups of varying hydrophobicity. These copolymers were constructed by adding amino acids stepwise to the hydrophilic block using solution phase chemistry. The self‐assembly behavior of all polymers was investigated using fluorimetry with a pyrene probe. In general, copolymers with more hydrophobic end groups exhibited lower critical aggregation concentrations (CACs). Fmoc‐terminated copolymers displayed the lowest CAC of 0.032 mg/mL and demonstrated little cytotoxicity when exposed to SW620 colorectal cancer cells. Transmission electron micrographs show the presence of multiple compartments within these spherical assemblies, which may prove useful in encapsulating medicinal substances. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5381–5389, 2008     

Well‐defined thermoresponsive dendritic polyamide/poly(N‐vinylcaprolactam) block copolymers

The first‐ and second‐generation well‐defined thermoresponsive amphiphilic linear–dendritic diblock copolymers based on hydrophilic linear poly(N‐vinylcaprolactam) and hydrophobic dendritic aromatic polyamide have been synthesized via reversible addition fragmentation chain transfer polymerization of N‐vinylcaprolactam by employing dendritic chain‐transfer agents possessing a single dithiocarbamate moiety at the focal point. These linear–dendritic copolymers exhibit reversible temperature‐dependent phase transition behaviors in aqueous solution as characterized by turbidity measurements using UV–vis spectroscopy. Their lower critical solution temperatures depend on the generation of the dendritic aromatic polyamides and the concentrations of the copolymer solutions. These amphiphilic copolymers are able to form nanospherical micelles in the aqueous solution as revealed by fluorescent spectroscopy, dynamic light scattering, and transmission electron microscope (TEM). The core–shell structure of micelles has been proved by ¹H NMR analyses of the micelles in D2O. The micelles loaded with indomethacin as a model drug showed high‐drug loading capacity and thermoresponsive drug release behavior. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3240–3250     

Thermosensitive t‐PLA‐b‐PNIPAAm tri‐armed star block copolymer nanoscale micelles for camptothecin drug release

Thermosensitive polylactide‐block‐poly(N‐isopropylacrylamide) (t‐PLA‐b‐PNIPAAm) tri‐armed star block copolymers were synthesized by atom transfer radical polymerization (ATRP) of monomer NIPAAm using t‐PLA‐Cl as macroinitiator. The synthesis of t‐PLA‐Cl was accomplished by esterification of star polylactides (t‐PLA) with 2‐chloropropionyl chloride using trimethylolpropane as a center molecule. FT‐IR, ¹H NMR, and GPC analyses confirmed that the t‐PLA‐b‐PNIPAAm star block copolymers had well‐defined structure and controlled molecular weights. The block copolymers could form core‐shell micelle nanoparticles due to their hydrophilic‐hydrophobic trait in aqueous media, and the critical micelle concentrations (CMC) were from 6.7 to 32.9 mg L^?1, depending on the system composition. The as‐prepared micelle nanoparticles showed reversible phase changes in transmittance with temperature: transparent below low critical solution temperature (LCST) and opaque above the LCST. Transmission electron microscopy (TEM) observations revealed that the micelle nanoparticles were spherical in shape with core‐shell structure. The hydrodynamic diameters of the micelle nanoparticles depended on copolymer compositions, micelle concentrations and media. MTT assays were conducted to evaluate cytotoxicity of the camptothecin‐loaded copolymer micelles. Camptothecin drug release studies showed that the copolymer micelles exhibited thermo‐triggered targeting drug release behavior, and thus had potential application values in drug controlled delivery. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4429–4439     

Preparation of methoxy poly(ethylene glycol)/polyester diblock copolymers and examination of the gel‐to‐sol transition

Diblock copolymers consisting of methoxy poly(ethylene glycol) (MPEG) and poly(?‐caprolactone) (PCL), poly(δ‐valerolactone) (PVL), poly(L ‐lactic acid) (PLLA), or poly(lactic‐co‐glycolic acid) (PLGA) as biodegradable polyesters were prepared to examine the phase transition of diblock copolymer solutions. MPEG–PCL and MPEG–PVL diblock copolymers and MPEG–PLLA and MPEG–PLGA diblock copolymers were synthesized by the ring‐opening polymerization of ?‐caprolactone or δ‐valerolactone in the presence of HCl · Et₂O as a monomer activator at room temperature and by the ring‐opening polymerization of L ‐lactide or a mixture of L ‐lactide and glycolide in the presence of stannous octoate at 130 °C, respectively. The synthesized diblock copolymers were characterized with ¹H NMR, IR, and gel permeation chromatography. The phase transitions for diblock copolymer aqueous solutions of various concentrations were explored according to the temperature variation. The diblock copolymer solutions exhibited the phase transition from gel to sol with increasing temperature. As the polyester block length of the diblock copolymers increased, the gel‐to‐sol transition moved to a lower concentration region. The gel‐to‐sol transition showed a dependence on the length of the polyester block segment. According to X‐ray diffraction and differential scanning calorimetry thermal studies, the gel‐to‐sol transition of the diblock copolymer solutions depended on their degrees of crystallinity because water could easily diffuse into amorphous polymers in comparison with polymers with a crystalline structure. The crystallinity markedly depended on both the distinct character and composition of the block segment. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5784–5793, 2004     

The synthesis and self‐assembly of ABA amphiphilic block copolymers containing styrene and oligo(ethylene glycol) methyl ether methacrylate in dilute aqueous solutions: Elevated cloud point temperatures for thermoresponsive micelles

A series of ABA amphiphilic triblock copolymers possessing polystyrene (PS) central hydrophobic blocks, one group with “short” PS blocks (DP = 54–86) and one with “long” PS blocks (DP = 183–204) were synthesized by atom transfer radical polymerization. The outer hydrophilic blocks were various lengths of poly(oligoethylene glycol methyl ether) methacrylate, a comb‐like polymer. The critical aggregation concentrations were recorded for certain block copolymer samples and were found to be in the range circa 10⁻⁹ mol L⁻¹ for short PS blocks and circa 10⁻¹² mol L⁻¹ for long PS blocks. Dilute aqueous solutions were analyzed by transmission electron microscopy (TEM) and demonstrated that the short PS block copolymers formed spherical micelles and the long PS block copolymers formed predominantly spherical micelles with smaller proportions of cylindrical and Y‐branched cylindrical micelles. Dynamic light scattering analysis results agreed with the TEM observations demonstrating variations in micelle size with PS and POEGMA chain length: the hydrodynamic diameters (D_H) of the shorter PS block copolymer micelles increased with increasing POEGMA block lengths while maintaining similar PS micellar core diameters (D_C); in contrast the values of D_H and D_C for the longer PS block copolymer micelles decreased. Surface‐pressure isotherms were recorded for two of the samples and these indicated close packing of a short PS block copolymer at the air–water interface. The aggregate solutions were demonstrated to be stable over a 38‐day period with no change in aggregate size or noticeable precipitation. The cloud point temperatures of certain block copolymer aggregate solutions were measured and found to be in the range 76–93 °C; significantly these were ∼11 °C higher in temperature than those of POEGMA homopolymer samples with similar chain lengths. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7739–7756, 2008     

Biofunctionalized block copolymer nanoparticles based on ring‐opening metathesis polymerization

We present an approach to the synthesis of biofunctionalized block copolymer nanoparticles based on ring‐opening metathesis polymerization; these nanoparticles may serve as novel scaffolds for the multivalent display of ligands. The nanoparticles are formed by the self‐assembly of diblock copolymers composed of a hydrophobic block and a hydrophilic activated block that can be functionalized with thiolated ligands in aqueous media. The activated block enables control over the orientation of the displayed ligands, which may be sugars, peptides, or proteins engineered to contain cysteine residues at suitable locations. The nanoparticle diameter can be varied over a wide range through changes in the composition of the block copolymer, and biofunctionalization of the nanoparticles has been demonstrated by the attachment of a peptide previously shown to inhibit the assembly of anthrax toxin. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 928–939, 2006     

Ambipolar charge transport in a donor–acceptor–donor‐type conjugated block copolymer and its gate‐voltage‐controlled thin film transistor memory

We demonstrate a fully conjugated donor–acceptor–donor (D–A–D) triblock copolymer, PBDTT–PNDIBT–PBDTT, which contains PBDTT as the donor block and PNDIBT as the acceptor block. The polymer was synthesized by end‐capping each block with a reactive unit, followed by condensation copolymerization between the two blocks. The physical, optical, and electrochemical properties of the polymer were investigated by comparing those of donor‐ and acceptor‐homopolymers (i.e., PBDTT and PNDIBT), which are the oligomeric monomers, and their blends. On using the newly synthesized block copolymer, ambipolar charge transport behavior was observed in the corresponding thin‐film transistor, and the behavior was compared to that of blend film of donor‐ and acceptor‐homopolymers. Owing to the presence of donor and acceptor blocks in a single polymer chain, it was found that the triblock copolymer can store two‐level information; the ability to store this information is one of the most intriguing challenges in memory applications. In this study, we confirmed the potential of the triblock copolymer in achieving distinct two‐stage data storage by utilizing the ambipolar charge trapping phenomenon, which is expected in donor and acceptor containing random and block copolymers in a thin‐film transistor. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3223–3235     

Synthesis,self‐assembly,and thermosensitivity of amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymers

In this article, the synthesis and self‐assembly of a novel well‐defined biocompatible amphiphilic POEGMA‐PDMS‐POEGMA triblock copolymer were studied. The copolymer was synthesized by atom transfer radical polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) using α,ω‐dibromo polydimethylsiloxane macroinitiator (Br‐PDMS‐Br). Br‐PDMS‐Br was synthesized through the esterification of α,ω‐hydroxypropyl polydimethylsiloxane and 2‐bromoisobutyryl bromide. The structures of the copolymers were confirmed by proton nuclear magnetic resonance spectroscopy, and gel permeation chromatography. The copolymers showed reversible aggregation in response to temperature cycles with a lower critical solution temperature (LCST) between 61 and 66 °C, as determined by ultraviolet‐visible spectrophotometry and dynamic light scattering. The LCST values increased in proportion to the length of the hydrophilic block and were lower than that of the POEGMA homopolymer. The self‐assembly behavior of the copolymers in aqueous solution was investigated by fluorescence spectroscopy and transmission electron microscopy. The critical micelle concentration value (1.08–0.26 10^?6 mol L^?1) decreased as the length of the POEGMA chain increased. The POEGMA‐PDMS‐POEGMA copolymers can easily self‐assemble into spherical micelles in aqueous solution. Such biocompatible block copolymers may be attractive candidates as ‘‘smart'' thermo‐responsive drug delivery systems. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2684‐2691     

Sol–gel transition behavior of biodegradable three‐arm and four‐arm star‐shaped PLGA–PEG block copolymer aqueous solution

Two types of temperature‐sensitive biodegradable three‐arm and four‐arm star‐shaped poly(DL ‐lactic acid‐co‐glycolic acid‐b‐ethylene glycol) (3‐arm and 4‐arm PLGA–PEG) were successfully synthesized via the coupling reaction of 3‐arm and 4‐arm PLGA and α‐monocarboxyl‐ω‐monomethoxypoly(ethylene glycol) (CMPEG). In dilute aqueous solutions, star PLGA–PEGs showed the temperature‐ and concentration‐dependent formation and aggregation of micelles over specific concentration and specific temperature. With increasing the molecular weight and the relative hydrophobicity of hydrophobic PLGA block, critical micelle temperature (CMT) decreased. Aqueous solution of 4‐arm PLGA–PEG started to form micelles at lower temperature and showed sharper temperature‐dependent growth in micelle size. These results are due to the enhanced hydrophobicity of PLGA block. On the other hand, at high concentration, two types of 3‐arm and 4‐arm PLGA–PEG showed sol–gel–sol transition behavior as the temperature was increased. The 3‐arm and 4‐arm PLGA–PEG showed sol–gel transition at higher polymer concentrations (above 24 wt %) than the PEG–PLGA–PEG triblock copolymer. As the molecular weight and the relative hydrophobicity of PLGA block increased, the critical gel concentration (CGC) decreased. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 888–899, 2006