Double Hydrophilic Diblock Copolymers Research Articles

Formation of Water-Soluble Complexes from Fullerene with Biocompatible Block Copolymers Bearing Pendant Glucose and Phosphorylcholine.

Double-hydrophilic diblock copolymers, PMPC100-block-PGEMAn (M100Gn), were synthesized via reversible addition-fragmentation chain transfer radical polymerization using glycosyloxyethyl methacrylate and 2-(methacryloyloxy)ethyl phosphorylcholine. The degree of polymerization (DP) of the poly(2-(methacryloyloxy) ethylphosphorylcholine) (PMPC) block was 100, whereas the DPs (n) of the poly(glycosyloxyethyl methacrylate) PGEMA block were 18, 48, and 90. Water-soluble complexes of C70/M100Gn and fullerene (C70) were prepared by grinding M100Gn and C70 powders in a mortar and adding phosphate-buffered saline (PBS) solution. PMPC can form a water-soluble complex with hydrophobic C70 using the same method. Therefore, the C70/M100Gn complexes have a core-shell micelle-like particle structure possessing a C70/PMPC core and PGEMA shells. The maximum amounts of solubilization of C70 in PBS solutions using 2 g/L each of M100G18, M100G48, and M100G90 were 0.518, 0.358, and 0.257 g/L, respectively. The hydrodynamic radius (Rh) of C70/M100Gn in PBS solutions was 55-75 nm. Spherical aggregates with a similar size to the Rh were observed by transmission electron microscopy. When the C70/M100Gn PBS solutions were irradiated with visible light, singlet oxygen was generated from C70 in the core. It is expected that the C70/M100Gn complexes can be applied to photosensitizers for photodynamic therapy treatments.

Synthesis, characterization and application of dual thermo- and solvent-responsive double-hydrophilic diblock copolymers of N-acryloylmorpholine and N-isopropylacrylamide

A series of double-hydrophilic diblock copolymers of N-acryloylmorpholine (NAMO) and N-isopropylacrylamide (NIPAm) with varying degree of polymerization were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. Structures and average molecular weights of these diblock copolymers were determined through 1H NMR spectra and SEC methods. Thermo-sensitivities and solvent-responsiveness of these copolymers were studied at varying temperatures in ethanol/water mixtures with different ethanol content. Beyond that, thermal behaviors during phase transitions were monitored by means of transmittance methods and DSC measurements, and the variation of aggregating structures in the interim was deduced basing on the results from DLS and TEM tests. Due to the cononsolvency effect of PNIPAm block along with the alcohol-insolubility of PNAMO block, thermo-responsive behaviors of copolymer chains would keep changing with the gradual addition of ethanol. Considering the thermo-responsive and the polar solvent-sensitive properties, we introduced the copolymers into a heavy oil/water mixing system, which possessed both changes of temperature and the attendance of polar groups. Tests results showed that the copolymer solutions did a quite good job on heavy oil viscosity reduction at the target temperature. The stimuli-response behavior of these copolymers endowed the polymer solution with the ability to interact with polar groups in heavy oil and form heavy oil/water emulsions, and made it possible to be used as a novel heavy oil viscosity reducer.

Lignosulfonate/diblock copolymer polyion complexes with aggregation-enhanced and pH-switchable fluorescence for information storage and encryption

Employing natural polymers as building blocks is favorable to construct sustainable functional materials and realize biomass utilization. Here we developed a series of supramolecular polyion complexes (PICs) composed of lignosulfonate and double-hydrophilic diblock copolymer poly(ethylene oxide-b-N, N-dimethylaminoethyl methacrylate) (PEO114-b-PDMAEMA24), which performed a blue emission with quenching-enhancing tendency and copolymer distribution inversion-involved assembling transformation at pH 5.6 and monotonic greenish-blue fluorescence promotion at pH 9.5 by increasing PEO114-b-PDMAEMA24 contents. Electrostatic interactions and multiple hydrogen bonds were revealed controlled the assembling behavior and affected the emission via altering the restriction of molecular motion, through-space conjunction, and non-luminous complexation. The multiple interacting sites and special topology of diblock copolymer contributed to the efficient fluorescence regulation. Information writing-erasing and encryption-decryption systems were established by utilizing emission intensity regulation and pH-responsive emission chromism. This work paved a new way to enhance lignin fluorescence and broadened potential applications of lignin composites in realms of sensing, imaging, monitoring, and anticounterfeiting.

Synthesis and self-assembly of polyzwitterionic phenylboronic acid-containing double hydrophilic block copolymers

Double hydrophilic block copolymers self-assemble into smart materials with promising applications in nanomedicine. However, such practical applications require thoroughly understanding the underlying mechanisms of this self-assembly process and the effects of external stimuli on the resulting materials. Thus, we report the post-polymerization modification of a pH-responsive double hydrophilic diblock copolymer (poly(ethylene oxide)-b-poly(4-vinyl pyridine)) by stimuli-responsive, diol-binding 2-bromomethyl-4-fluorophenylboronic acid and the comprehensive study of the self-assembly properties of this polyzwitterionic polymer for potential applications in the delivery of functional diols, including pharmaceutical drugs, steroids and sugars. For this purpose, we performed simple, robust and reproducible quaternization reactions at three different degrees (25, 50 and 100%) by varying the composition of the initial mixture and confirmed full control over the degree of quaternization by proton nuclear magnetic and infrared spectroscopy. Our results show that the degree of quaternization strongly affects the solubility of these polymers in basic solutions because PBA adopts a tetragonal conformation with a negative charge on boron at pH values higher than the pKA of PBA. Nevertheless, the specific PBA (anionic vs neutral) form of these polymers can be differentiated by 11B NMR, regardless of the degree of quaternization. In turn, the pH of the solvent affected the intensity of the NMR signals, thus suggesting the formation of kinetically frozen nanoparticles, in line with the results from both static and dynamic light scattering, with no indication of particle dissociation at low concentrations. Moreover, electrophoretic light scattering showed linear, albeit opposite (direct and inverse) correlations between the degree of quaternization and the zeta potential in water and 0.1 M HCl, respectively. When adsorbed to a mica surface, these nanoparticles predominantly displayed globular shapes under atomic force microscopy. Therefore, our high-throughput and low-cost nanofabrication method combining the stimuli-responsive behavior of a double hydrophilic block copolymer with the unique chemical properties of pH-responsive diol-binding phenylboronic acid functional groups establishes an experimental paradigm for preparing nanocarriers for biomedical applications, such as targeted drug delivery.

Theoretical study of thermoresponsive dendritic polymeric micelles: Micellar phase control and the extraction of organic molecules by temperature effects

Smart dendritic micelles are stimuli-sensitive dendritic polymeric micelles that combine the characteristics of double-hydrophilic diblock copolymers and hyperbranched dendritic molecules. The micellar phase control of the smart dendritic micelles consisting of Boltorn-H40 hyperbranched dendrimer and poly(N,N-diethylacrylamide)-b-poly(2-(dimethylamino)ethyl methacrylate) diblock copolymer (H40-PDEA–PDMA) and their capacity to extract organic molecules in an aqueous environment are explored using dissipative particle dynamics simulations. The mesoscopic outcomes show that the H40-PDEA–PDMA micelles exhibit two consecutive low critical solution temperatures and three specific conformations with a cloud point: (1) stable dendritic micelles with a dendritic-H40 core and double micellar corona (PDEA-PDMA) at room temperature, (2) dendritic micelles with a core-shell (dendrimer-H40-PDEA) and PDMA corona at intermediate temperature, and (3) polymeric particles with a dendritic-H40 core and polymeric double-shell (PDEA-PDMA) at high temperature. The thermal behaviour of smart dendritic micelles is exploited for the extraction of rose bengal organic molecules from an aqueous solution. The extraction process of organic molecules consists of three transitory stages: molecular loading on the dendritic-H40 core, molecular encapsulation via core-shell formation, and the generation of compact polymeric particles with a dendritic-H40 core and polymeric double-shell via a cloud point through temperature effects. All micellar phases and transitory states that include the H40-PDEA–PDMA micelles in the thermal process are analysed in detail. Our simulations are in agreement with the experimental outcomes observed for this smart dendritic material.

Azo Coupling Reaction Induced Macromolecular Self-Assembly in Aqueous Solution.

This communication reported azo coupling reaction induced macromolecular self-assembly in aqueous solution. Diblock copolymer (PEG-b-PSNHBoc) consisting of a hydrophilic PEG block, and a hydrophobic N-Boc protected poly(p-vinylaniline) block was synthesized by RAFT polymerization. Then double hydrophilic diblock copolymer (PEG-b-PSN2+) composed of PEG and PS based macromolecular diazonium salts was prepared by the diazotization of PEG-b-PSNH2, which was obtained by deprotection of PEG-b-PSNHBoc. As N,N-dimethylaniline was gradually added into the freshly prepared PEG-b-PSN2+ aqueous solution, the azo coupling reaction between N,N-dimethylaniline and diazonium salts took place, which would lead to the generation of azobenzene pendants. Due to the poor solubility of azobenzene pendants in water, the formed hydrophobic polymeric chains aggregated to form the self-assembly colloidal particles. By incorporating a fluorescent group into the aniline, the aggregates formed through azo coupling reaction induced macromolecular self-assembly showed enzyme-triggered fluorescent behaviors.

Self-assembly/disassembly of giant double-hydrophilic polymersomes at biologically-relevant pH.

Self-assembled giant polymer vesicles prepared from double-hydrophilic diblock copolymers, poly(ethylene oxide)-b-poly(acrylic acid) (PEO-PAA) show significant degradation in response to pH changes. Because of the switching behavior of the diblock copolymers at biologically-relevant pH environments (2 to 9), these polymer vesicles have potential biomedical applications as smart delivery vehicles.

Mussel-inspired construction of thermo-responsive double-hydrophilic diblock copolymers-decorated reduced graphene oxide as effective catalyst supports for highly dispersed superfine Pd nanoparticles.

Well-dispersed ultrafine palladium nanoparticles supported by reduced graphene oxide functionalized with catechol-terminated thermo-responsive block copolymer (PdNPs@BPrGO) were successfully constructed for highly efficient heterogeneous catalytic reduction. We first synthesized a novel temperature-responsive episulfide-containing double-hydrophilic diblock copolymer, poly(poly(ethylene glycol) methyl ether methacrylate-co-2,3-epithiopropyl methacrylate)-block-poly(N-isopropylacrylamide) (P(PEGMA-co-ETMA)-b-PNIPAM), through a reversible addition-fragmentation chain transfer (RAFT) polymerization utilizing a chain-transfer agent with a catechol unit as the end group. The obtained block copolymers can be facilely anchored to the surface of GO via mussel-inspired chemistry. The PdNPs were loaded on GO decorated with block copolymer brushes (BPrGO) as a support via the in situ reduction of palladium precursors with the episulfide ligands of the block copolymer as a stabilizer. The resulting PdNPs@BPrGO nanohybrid catalyst had good water dispersibility and stability. Furthermore, a low dosage of PdNPs@BPrGO catalyst exhibited excellent catalytic performance in the reduction of methylene blue and nitrophenols. The performance was attributed to the ability of PdNPs@BPrGO to facilitate the diffusion of reactants compared to PdNPs@GO without polymer modification. PdNPs@BPrGO also possessed an interesting temperature-responsive catalytic property due to the reversible "coil-to-globule" phase transition behaviour of PNIPAM blocks onto the surface of catalyst. The PdNPs@BPrGO catalyst was successfully recovered and reused five times without any detectible loss in catalytic activity, demonstrating its great potential in a wide range of industrial catalytic applications.

Fabrication of pH- and Thermoresponsive Three-Layered Micelles via Host-Guest Interactions.

Well-defined β-cyclodextrin (β-CD)-terminated double hydrophilic diblock copolymers (DHBCs), β-CD- poly(di(ethylene glycol) methyl ether methacrylate) (PMEO2 MA)-b-poly(2-(diethylamino)ethyl methacrylate) (PDEA) (BP1) and β-CD-PDEA-b-PMEO2 MA (BP2), are synthesized via sequential atom transfer radical polymerizations of di(ethylene glycol) methyl ether methacrylate and 2-(diethylamino)ethyl methacrylate using alkynyl-functionalized initiator, followed by click reactions with an excess of mono-azido-substituted β-cyclodextrin (β-CD-N3 ). The micellization behavior of these as-prepared DHBCs in aqueous solutions suffers from insufficient colloidal stabilities at basic pH and high temperatures (e.g., pH 9 and 45 °C), resulting in the formation of macroscopic precipitations. However, the stabilities of colloidal nanoparticles can be remarkably enhanced as a result of the convenient formation of three-layered micelles by taking advantage of host-guest interactions of BP1/BP2 and Ad-terminated poly(ethylene glycol). The pH- and thermoresponsive three-layered micelles with enhanced stability may augur promising applications in targeted drug delivery and controlled intelligent release.

Vesicles of double hydrophilic pullulan and poly(acrylamide) block copolymers: a combination of synthetic- and bio-derived blocks

The formation of vesicular structures with average diameters from 200 to 300 nm consisting of double hydrophilic diblock copolymers pullulan-b-poly(N,N-dimethylacrylamide) and pullulan-b-poly(N-ethylacrylamide) in aqueous solution is described.

Organized Polymeric Submicron Particles via Self-Assembly and Cross-Linking of Double Hydrophilic Poly(ethylene oxide)-b-poly(N-vinylpyrrolidone) in Aqueous Solution

The formation of submicron particles consisting of double hydrophilic diblock copolymers of poly(ethylene oxide) and poly(N-vinylpyrrolidone) (PEO-b-PVP) in aqueous solution is described. Block copolymers were synthesized via reversible deactivation radical polymerization using a PEO-xanthate as macro RAFT/MADIX chain transfer agent. Increasing polymer concentrations in aqueous solutions, the block copolymer is able to self-assemble into spherical structures with apparent hydrodynamic diameters in the range between 200 nm and 2 μm. The self-assembly was further improved by copolymerization with a more hydrophilic monomer, N-vinylimidazole (VIm). Submicron particles from PEO-b-P(VP-co-VIm) were preserved via cross-linking utilizing imidazolium formation with a dihalogenide. Thus, submicron double hydrophilic particles were obtained that are stable in organic solvents and under high dilution. Almost quantitative formation of submicron particles with an average diameter of 200 nm can be afforded by the self-assembly in the polar organic solvent DMF and subsequent crosslinking as well. Furthermore, the obtained particles show a promising ability to incorporate various molecules for delivery and release, here exemplified with simple dyes.

Nitric Oxide (NO) Cleavable Biomimetic Thermoresponsive Double Hydrophilic Diblock Copolymer with Tunable LCST

The fabrication of responsive biomimetic polymers that can respond to externally applied stimuli has received considerable attention over the past few years due to the variety of potential applications. Herein, we report a convenient method to fabricate a thermoresponsive diblock copolymer that is sensitive to a biological messenger molecule, nitric oxide (NO). A well-defined thermoresponsive double hydrophilic block copolymer (DHBC) of poly(ethylene glycol)-b-poly(N-isopropylacrylamide) (PEG-b-PNIPAM) was initially synthesized via atom radical transfer polymerization (ATRP) using a PEG-Cl macroinitiator including an o-nitroaniline motif. The o-nitroaniline derivative was subjected to reduction in the presence of a reducing agent (zinc powder), yielding DHBC with a single amide-functionalized o-phenylenediamine moiety (an efficient NO-reactive group) at the chain junction point. Upon addition of a near equivalent amount of NO (relative to the o-phenylenediamine residues), the o-phenylenediamine groups wer...

Self-assembly of multi-responsive poly(N-isopropylacrylamide)-b-poly(N,N-dimethylaminopropylacrylamide) in aqueous media

Stimuli responsive double hydrophilic diblock copolymers poly(N-isopropylacrylamide)-b-poly(N,N-dimethylaminopropylacrylamide) (PNIPAM-b-PDMPA) with constant degree of polymerization (DP) of PNIPAM (=127) and varying DP of PDMPA (=31 and 66) were synthesized by RAFT polymerization, and characterized by NMR, FTIR and GPC. In dilute aqueous solutions, the copolymers remain as unimers in equilibrium with loosely bound aggregates and form aggregates with PNIPAM core in the presence of NaCl or at temperatures above the LCST of PNIPAM. However, at higher temperatures i.e. above cloud point temperature (CPT) of PNIPAM127-b-PDMPA66, core–shell micelles are formed with PNIPAM core. The CPT of both block copolymers decrease in the presence of NaCl and in acidic pH, but increases with increase in DP of PDMPA. The copolymer showed enhanced surface activity in the presence of NaCl. The temperature dependent micellization observed from NMR is supported by turbidity and fluorescence. PDMPA is highly protonated in acidic pH; cryo-TEM and SANS confirm the formation of threadlike micelles in the presence of SDS.

PEG‐Amine‐Initiated Polymerization of Sarcosine N‐Thiocarboxyanhydrides Toward Novel Double‐Hydrophilic PEG‐b‐Polysarcosine Diblock Copolymers

Amino acid N-thiocarboxyanhydride (NTA), the thioanalog of N-carboxyanhydride (NCA), is much more stable than NCA against moisture and heat. The convenient monomer synthesis without rigorous anhydrous requirements makes the ring-opening polymerization of NTA a competitive alternative to prepare polypeptoid-containing materials with potential of large-scale production. Polysarcosines (PSars) with high yields (>90%) and low polydispersities (<1.2) are synthesized from sarcosine N-thiocarboxyanhydride (Sar-NTA) at 60 °C initiated by primary amines including poly(ethylene glycol) amine (PEG-NH2 ). The lengths of PSar segments are controlled by various feed ratios of Sar-NTA to initiator. PEG-b-PSar products, a class of novel double-hydrophilic diblock copolymers, are effective in stabilizing oil-in-water emulsions at nano- and microscale, which demonstrates promising encapsulation applications in food, cosmetics, and drug delivery. Due to the different solubility of PEG and PSar blocks, PEG-b-PSar copolymers form micelles in organic solvents with the capability to incorporate metal cations including Cu(2+) and Ni(2+) .

Preparation and self-assembly of double hydrophilic poly(ethylethylene phosphate)-block-poly[2-(succinyloxy)ethyl methacrylate] diblock copolymers for drug delivery

This work focuses on the synthesis and self-assembly of biodegradable and anionic double hydrophilic diblock copolymers (DHBCs) poly(ethylethylene phosphate)-block-poly[2-(succinyloxy)ethyl methacrylate] (PEEP-b-PSEMA) with different molecular weights and compositions, which were prepared via a combination of ring opening polymerization (ROP), atom transfer radical polymerization (ATRP) and polymer reaction. The chemical structures of these well-defined diblock copolymers were confirmed by 1H NMR and FT-IR analyses. GPC results indicated that the copolymers showed symmetric peak and relatively narrow polydispersities. Subsequently, pH-responsive micellization behaviors of PEEP-b-PSEMA diblock copolymers were investigated by fluorescence probe method, dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. The results demonstrated that these diblock copolymers were able to self-assemble into micelles with various sizes depending on the variation of pH values. Naproxen (NAP), a poorly water-soluble drug, was selected as the model drug and encapsulated into the core of micelles via dialysis method. The in vitro release behavior of NAP from these micelles was pH-dependent and could be accelerated in the presence of phosphodiesterase I which could promote the degradation of polyphosphoesters. Cytotoxicity tests by MTT assay showed that these block copolymers possessed favorable biocompatibility against HeLa cells, revealing that this kind of biodegradable, biocompatible and pH-responsive block copolymer would be served as a promising material for drug delivery.

Water-soluble macromolecular co-assemblies of star-shaped polyelectrolytes

This mini-review reports on complex macromolecular architectures (interpolyelectrolyte complexes) based on star-shaped polyelectrolytes. These complexes can be prepared in aqueous media via electrostatically driven co-assembly of star-shaped polyions (a) with oppositely charged linear homopolyelectrolytes or (b) with oppositely charged double hydrophilic (ionic/non-ionic) diblock copolymers. In case (a), the complexes can be water-soluble if the charge of the star-shaped macromolecule is only partially compensated by a linear polyion. In case (b), the complexes retain their solubility in aqueous media even under a full charge compensation of the polymeric components. In both cases, the complex macromolecular architectures based on star-shaped polyelectrolytes are characterized by a distinct compartmentalized structure of a micellar (‘core–corona’) type with an insoluble core, which is assembled from coupled monomer units of the oppositely charged polymeric components, and a hydrophilic, either ionic or non-ionic, corona. Copyright © 2012 Society of Chemical Industry

Micellar interpolyelectrolyte complexes formed by star-shaped poly(acrylic acid) with double hydrophilic cationic diblock copolymer

Micellar interpolyelectrolyte complexes formed by star-shaped poly(acrylic acid) with double hydrophilic cationic diblock copolymer

Synthesis and micellization of thermoresponsive galactose‐based diblock copolymers

AbstractThermoresponsive double hydrophilic diblock copolymers poly(2‐(2′‐methoxyethoxy)ethyl methacrylate‐co‐oligo(ethylene glycol) methacrylate)‐b‐poly(6‐O‐methacryloyl‐D‐galactopyranose) (P(MEO2MA‐co‐OEGMA)‐b‐PMAGP) with various compositions and molecular weights were obtained by deprotection of amphiphilic diblock copolymers P(MEO2MA‐co‐OEGMA)‐b‐poly(6‐O‐methacryloyl‐1,2:3,4‐di‐O‐isopropylidene‐D‐galactopyranose) (P(MEO2MA‐co‐OEGMA)‐b‐PMAlpGP), which were prepared via reversible addition‐fragmentation chain transfer (RAFT) polymerization using P(MEO2MA‐co‐OEGMA) as macro‐RAFT agent. Dynamic light scattering and UV–vis studies showed that the micelles self‐assembled from P(MEO2MA‐co‐OEGMA)‐b‐PMAlpGP were thermoresponsive. A hydrophobic dye Nile Red could be encapsulated by block copolymers P(MEO2MA‐co‐OEGMA)‐b‐PMAGP upon micellization and released upon dissociation of the formed micelles under different temperatures. The galactose functional groups in the PMAGP block have specific interaction with HepG2 cells, and P(MEO2MA‐co‐OEGMA)‐b‐PMAGP has potential applications in hepatoma‐targeting drug delivery and biodetection. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Biostable Poly(ethylene oxide)-b-poly(methacrylic acid) Micelles forpH-triggered Release of Doxorubicin

ABSTRACT − pH-sensitive cross-linked polymeric micelles were synthesized by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) with calcium ions as micellar templates. An anticancer drug, doxorubicin (DOX) was conjugated on the cross-linked ionic cores of micelles via acid-labile hydrozone bonds. The result-ing DOX-conjugated, pH-sensitive micelles are stable at physiological conditions, whereas the release of DOX was sig-nificantly increased at the acidic pH. Such micelles were internalized to lysosomes, and acidic pH in lysosomes triggers the release of DOX upon internalization in MCF-7 breast cancer cells. The released DOX entered the cell nucleus and even-tually killed cancer cells. Therefore, these data demonstrate that the pH-sensitive micelles could be a promising nanocarrier for delivery of anticancer drug, DOX.Key words− Doxorubicin, Block ionomer, Calcium, Cross-linked, Polymeric micelles Self-assembled polymeric micelles formed by amphilphilic block copolymers have been utilized as potential drug delivery vehicles for anti-cancer drugs (Allen et al., 1999; Cohy, 2005; Croy et al., 2006; Duncan, 2003; Kabanov et al., 2009; Lavasanifara et al., 2002; Riess, 2003; Rosler, 2001). They are nanoparticles prepared by self-assembly of block copolymers consisted of two different blocks, which are hydrophilic and hydrophobic blocks. Advantages of polymeric micelles for tumor targeting include core-shell type architecture with nanoscale size (10 to 100 nm in diameter), which prolong cir-culation time of polymeric micelles in the body. Hydrophilic nonionic shell such as poly(ethylene oxide) allows for long-cir -culation of nanocarriers by reducing non-specific uptake and clearance by the macrophages of the reticuloendothelial sys-tem (RES). Interestingly, such polymeric nanocarriers have been shown to accumulate in tumors and improve anti-tumor activity of anti-cancer drugs (Alakhov et al., 1999; Yokoyama et al., 1999; Lavasanifara et al., 2002; Duncan, 2003; Davis et al., 2008), by the enhanced permeability and retention effect (EPR effect) (Maeda, 2001). Nanofabrication of the polymeric micelles has been exten-sively advanced through employment of double hydrophilic diblock copolymers, one of which is hydrophilic ionic block and the other is hydrophilic nonionic block. These copolymers spontaneously form nanoparticles called “block ionomer com-plexes (BIC)” or “polyion complex micelles (PIC)”, through electrostatic interaction with oppositely charged molecules. However, the stability of polymeric micelles can be signif-icantly affected by environmental factors such as pH, ionic strength, dilution and shear forces after administration in the blood stream, which may lead to loss of their ability to deliver chemotherapeutic drugs to target tissues.In order to address this problem, nano-sized polymeric micelles based on a cross-linked network of amphiphilic block copolymers have been developed for delivery of anti-cancer drugs (Bronich et al., 2005; Bontha et al., 2006; Kim et al., 2009; Kim et al., 2010). It contains several key features such as cross-linked ionic core, a hydrophilic PEO shell and nanos-cale size. Due to cross-linked ionic cores of micelles, these micelles exhibited distinctive properties as drug delivery carriers, such as their high loading capacity, high stability, and responses to environmental stimuli, such as ionic strength, pH, and temperature (Bontha et al., 2006; Kim et al., 2009).Furthermore, the entry of the cross-linked micelles is inhibited in tight junctions in normal epithelial cells but permitted in cancer cells that do not form tight junctions, via caveolae-mediated endocytosis (Sahay et al., 2010). These favorable characteristics of cross-linked micelles can lead to develop-

Self-assembly of double hydrophilic block copolymers in concentrated aqueous solution

We report the unusual aqueous (micro)phase separation of binary mixtures of two biocompatible, hydrophilic homopolymers and the corresponding double-hydrophilic diblock copolymers of poly(ethylene oxide) (PEO) and poly[2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC). SAXS analysis of these double hydrophilic block copolymers in concentrated aqueous solution shows highly hydrated nano-structures and a hydration mechanism is proposed based on these data.