Novel double hydrophilic block copolymers based on poly(p‐hydroxystyrene) derivatives and poly(ethylene oxide)

The synthesis of three series of double hydrophilic block copolymers (DHBCs), consisting of poly(ethylene oxide) as the neutral water soluble block and a second polyelectrolyte block of variable chemistry, is described. The synthetic scheme involves the anionic polymerization of poly(p‐tert‐butoxystyrene‐b‐ethylene oxide) (PtBOS‐PEO) amphiphilic block copolymer precursors followed by the acidic hydrolysis of the hydrophobic poly(p‐tert‐butoxystyrene) (PtBOS) block to an annealed anionic polyelectrolyte poly(p‐hydroxystyrene) (PHOS) block. The PHOS block was subsequently transformed into a high charge density annealed cationic polyelectrolyte namely poly[3,5‐bis(dimethylaminomethylene) hydroxystyrene] (NPHOS), via aminomethylation. Finally, the NPHOS block was transformed into a quenched polyelectrolyte, namely quaternized poly[3,5‐bis(dimethylaminomethylene) hydroxystyrene] (QNPHOS) block by reaction with CH₃I. The solution properties of the different series of the above block polyelectrolyte copolymers have been investigated using static, dynamic and electrophoretic light scattering, turbidimetry, and fluorescence spectroscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 5790–5799, 2007     

Fusiform micelles from nonlinear poly(ethylene glycol)/polylactide copolymers as biodegradable drug carriers

PEG-PLA copolymers with dumbbell- and Y-shaped structures are prepared. They can self-assemble from nanoparticles to micro-sized fusiform micellar particles in aqueous solution. In particular the micelles formed by the (PLA)2-PEG-(PLA)2 particles show a better drug loading capacity and encapsulation efficiency than those formed by linear MPEG-PLA. In vitro studies show that the particles formed by Y-shaped copolymers show a particularly quick drug release. The copolymers have good biocompatibility with low cytotoxicity. These unique self-assembled systems thus have many possible biomedical applications, such as a sustained delivery of high-dosed water insoluble drugs, quick effective drugs for trauma, controlled delivery of the oral-administration drugs, and so forth.     

Associative block copolymers comprising poly(N‐isopropylacrylamide) and poly(ethylene oxide) end‐functionalized with a fluorophilic or hydrophilic group. Synthesis and aqueous solution properties

A series of block copolymers comprising poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene oxide) (PEO) end‐functionalized with a quaternary ammonium group (R_Q) was synthesized by free‐radical polymerization of N‐isopropylacrylamide with well‐defined R_QPEO macroazoinitiators. The radical termination occurred mainly by disproportionation, as confirmed by combining the data from size exclusion chromatography (SEC) and rheology measurements. The copolymers denoted R_QE_xN_y differ in type of the terminal group [F_Q = C₈F₁₇(CH₃)₂N⁺ or M_Q = (CH₃)₃N⁺] and in the length of the PEO (E_x; x = 4, 6, or 10 K) and PNIPAM (N_y; y = 7 or 17–19 K) blocks. The type of the terminal group determined the behavior of the block copolymers in the dilute and semidilute regime. Self‐assembled species formed by both F_Q and M_Q modified block copolymers were detected by static light scattering measurements at 25 °C and above the lower critical solution temperature (LCST). The LCST of the block copolymers depended on the type of the R_Q group and the length of the blocks. F_Q‐modified copolymers form elastic gels below and above the LCST. It was inferred that the F_Q groups and the PNIPAM blocks form segregated microdomains that serve as junctions to maintain a viscoelastic network. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5736–5744, 2004     

Synthesis and characterization of amphiphilic block copolymer of polyphosphoester and poly(L‐lactic acid)

Aliphatic polyesters and polyphosphoesters (PPEs) have received much interest in medical applications due to their favorable biocompatibility and biodegradability. In this work, novel amphiphilic triblock copolymers of PPE and poly(L ‐lactic acid) (PLLA) with various compositions were synthesized and characterized. The blocky structure was confirmed by GPC analyses. These triblock copolymers formed micelles composed of hydrophobic PLLA core and hydrophilic PPE shell in aqueous solution. Critical micellization concentrations of these triblock copolymers were related to the polymer compositions. Incubation of micelles at neutral pH followed by GPC analyses revealed that these polymer micelles were hydrolysized and resulted in decreased molecular weights and small oligomers, whereas its degradation in basic and acid mediums was accelerated. MTT assay also demonstrated the biocompatibility against HEK293 cells. These biodegradable polymers are potential as drug carriers for biomedical application. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6425–6434, 2008     

Organometallic-polypeptide block copolymers: synthesis and self-assembly of poly(ferrocenyldimethylsilane)-b-poly(epsilon-benzyloxycarbonyl-L-lysine)

A new type of metallopolymer-polypeptide block copolymer poly(ferrocenyldimethylsilane)-b-poly (epsilon-benzyloxycarbonyl-L-lysine) was synthesized by ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride initiated by using a primary amino-terminated poly(ferrocenyldimethylsilane). Studies on the self-organization behavior of this polypeptide block copolymer in both the bulk state and in solution were performed. In the bulk state, a cylindrical-in-lamellar structure was observed in a compositionally asymmetric sample. Rod-like micelles with a polyferrocenylsilane core formed in a polypeptide-selective solvent alone or in the presence of a common solvent. Significantly, an additional small quantity of the common solvent assisted the formation of longer micelles and micelles with better shape-regularity. This is attributed to a decrease in the number of nucleation events and PFS core reorganization effects.     

Responsive vesicles from the self-assembly of crystalline-coil polyferrocenylsilane-block-poly(ethylene oxide) star-block copolymers

We demonstrate the synthesis and characterization of star‐shaped crystalline‐coil block copolymers with four arms consisting of an inner block of poly(ethylene oxide) and an outer semicrystalline compartment of poly(ferrocenyldimethylsilane), [PEO₅₀‐b‐PFDMS₃₅]₄. The materials were synthesized by transition‐metal‐catalyzed ring‐opening polymerization of dimethylsila[1]ferrocenophane in the presence of silane‐functionalized four‐arm PEO stars as macroinitiators and they exhibited a moderate polydispersity (PDI?1.4). Self‐assembly in mixtures of THF and different alcohols as selective solvents for the PEO block resulted in the formation of semicrystalline vesicles (ethanol, 1‐butanol) or large, rather ill‐defined, spherical structures (methanol). Further, both the rate of addition of the selective co‐solvent and the overall solvent/non‐solvent ratio drastically affected the size and stability of the self‐assembled particles. We could also show that a photoacid generator, as a model for an active substance, can be encapsulated and the UV‐induced generation of HCl resulted in a straightforward degradation of the organometallic vesicles.     

Chiroptical aggregates from block copolymer bearing amino acid moieties in aqueous solution

Optically active poly(ethylene glycol) monomethyl ether‐b‐poly(methacryloyl‐L ‐leucine methyl ester) (denoted as MPEG‐b‐PMALM) copolymers were prepared via atom transfer radical polymerization (ATRP), using bromine (Br) end‐capped poly(ethylene glycol) monomethyl ether (denoted as MPEG‐Br) as macroinitiator in the presence of CuBr/tris(2‐dimethylaminoethy1)amine (Me₆TREN) as catalytic system. Broad range of morphologies, such as spherical, cylindrical, and vesicular micelles, which were prepared by initially dissolving prepared polymer in organic solvent at different concentration followed by addition various amount of water before dialysis against water to remove any added solvent, was observed by transmission electron microscope (TEM). More detailed chiroptical properties of the micelles/aggregates in aqueous solution were evaluated by circular dichroism (CD) spectroscopy as a function of micelles morphologies, polymer concentration, solvents employed, temperature, etc. The micellar solutions exhibit almost the same CD spectra regardless of its morphologies. The intensity of the CD spectra of the cylindrical micelles decreased in the molar ellipticities as the micellar concentration in water was increased. The Cotton effect was markedly changed when the solvent hydrophobicity was changed by addition of trifluoromethyl ethanol (TFME) to water. The intensity of the CD spectra decreased not too much within the temperature range from 20 °C to 90 °C, indicating good stability of the micelles upon temperature variation. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 1345–1355, 2009     

Multiple morphologies from a novel diblock copolymer containing dendronized polymethacrylate and linear poly(ethylene oxide)

A novel amphiphilic diblock copolymer, consisting of dendronized polymethacrylate‐b‐poly(ethylene oxide), was synthesized via atom transfer radical polymerization; from it, micellelike aggregates of various morphologies, prepared under near‐equilibrium conditions, were studied with transmission electron microscopy and scanning electron microscopy. The effects of various factors on the aggregate morphologies of the amphiphilic copolymer, such as the water content, the copolymer concentration, and the type of common solvent, were investigated systematically. The unique architecture of the block copolymer led to morphological variety and peculiarities such as dendritic and shuttle‐shaped aggregates, which could be attributed to the effective packing of the bulky side chains, that is, another driving force for the aggregates. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2291–2297, 2005     

Molecular captain: A light‐sensitive linker molecule in poly(ethylene glycol)‐poly(L‐alanine)‐poly(ethylene glycol) triblock copolymer directs molecular nano‐assembly,conformation, and sol‐gel transition

We report a poly(ethylene glycol)‐poly(L ‐alanine)‐azobenzene‐poly(L ‐alanine)‐poly(ethylene glycol) (PEG‐PA‐Z‐PA‐PEG) as a temperature and light sensitive polymer. The poly(ethylene glycol)‐poly(L ‐alanine) diblock copolymers with a flexible‐rigid block structure were coupled by an azobenzene group that undergoes a reversible configurational change between “trans” and “cis” upon exposure to UV and vis light. The single azobenzene molecule embedded in the middle of a block copolymer with a flexible (shell)‐rigid (core) structure significantly affected molecular assembly, micelle size, polypeptide secondary structure, and sol‐to‐gel transition temperature of the polymer aqueous solution, depending on its exposure to UV or vis light. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization of thermoresponsive amphiphilic block copolymers incorporating a poly(ethylene oxide‐stat‐propylene oxide) block

Amphiphilic BuO‐(PEO‐stat‐PPO)‐block‐PLA‐OH diblock and MeO‐PEO‐block‐(PEO‐stat‐PPO)‐block‐PLA‐OH triblock copolymers incorporating thermoresponsive poly(ethylene oxide‐stat‐propylene oxide) (PEO‐stat‐PPO) blocks were prepared by ring‐opening polymerization of lactide (LA) initiated by macroinitiators formed from treating BuO‐(PEO‐stat‐PPO)‐OH and MeO‐PEO‐block‐(PEO‐stat‐PPO)‐OH with AlEt₃. MeO‐PEO‐block‐(PEO‐stat‐PPO)‐OH was prepared by coupling MeO‐PEO‐OH and HO‐(PEO‐stat‐PPO)‐OH, followed by chromatographic purification. The cloud points of 0.2% aqueous solutions are between 36 and 46 °C for the diblock copolymers that contain a 50 wt % EO thermoresponsive block and 78 °C for the triblock copolymer that contains a 75 wt % EO thermoresponsive block. Variable temperature ¹H NMR spectra recorded on D₂O solutions of the diblock copolymers display no PLA resonances below the cloud point and fairly sharp PLA resonances above the cloud point, suggesting that desolvation of the thermoresponsive block increases the miscibility of the two blocks. Preliminary characterization of the micelles formed in aqueous solutions of BuO‐(PEO‐stat‐PPO)‐block‐PLA‐OH conducted using laser scanning confocal microscopy and pulsed gradient spin echo NMR point to significant changes in the size of the micellar aggregates as a function of temperature. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5156–5167, 2005     

Electrochemical behavior of high-molecular-weight poly(ferrocenylsilane) films in aqueous electrolyte solutions

The electrochemical behavior of high-molecular-weight poly(ferrocenyldimethylsilane) films and poly(ferrocenylmethylphenylsilane) films, which contained about 2.8 × 10⁻⁶ mol cm⁻² ferrocene sites in eight kinds of aqueous electrolyte solutions, was investigated with cyclic voltammetry (CV). In some aqueous electrolyte solutions, the CV peak currents diminished gradually with an increase in the scanning times, whereas in other aqueous electrolyte solutions, stable and repeated cyclic voltammograms were obtained. The polymer films were poor-solvent-swollen in aqueous electrolyte solutions, and this resulted in a high resistivity of mass transfer and a slow rate of electrode reaction; therefore; quasireversible or irreversible CV processes were obtained. The kinetic parameters of the film-electrode processes, such as the surface transfer coefficient, the apparent diffusion coefficient, and the standard rate constant for electron transfer, for the two films in aqueous LiClO₄ solutions were measured, and the electrode process mechanism of the films was examined. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2245–2253, 2004