Hydrophobic Middle Block Research Articles

Enhancing membrane modulus of giant unilamellar lipid vesicles by lateral co-assembly of amphiphilic triblock copolymers

We report a facile, but robust approach to fabricate structurally stable giant unilamellar vesicles (GUVs), on which a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membrane was made rigid by introducing amphiphilic block polymers. Particularly, we found that lateral co-assembly of an amphiphilic triblock copolymer (ATC) structured with a hydrophobic middle block and long molecular weight (20 K g/mol) hydrophilic end blocks remarkably enhanced the stretching modulus (k) of GUVs. When the membrane composition was optimized, the k value of ATC-hybridized GUVs increased to 6.2 × 108 Pa, which was approximately 10-fold higher than that of DPPC GUVs, thus leading to a much longer half-life. Moreover, we demonstrated that our ATC-hybridized GUVs enabled development of a fascinating vesicular model, which shows great potential as a structurally stable cell membrane mimic.

Oligopeptide-modified hydrophobic and hydrophilic polymers as antifouling coatings

Amphiphilic block copolymers have been extensively studied for their antifouling and fouling-release properties. Herein the authors report amphiphilic polymers based on two triblock copolymers with opposite-polarity backbones: polystyrene-block-poly(dimethylsiloxane-stat-vinylmethylsiloxane)-block-polystyrene (PS-b-P(DMS-stat-VMS)-b-PS), which contains a hydrophobic middle block, and polystyrene-block-poly[(ethylene oxide)-stat-(allyl glycidyl ether)]-block-polystyrene (PS-b-P(EO-stat-AGE)-b-PS), which contains a hydrophilic middle block. These two triblock copolymers were modified with two different non-natural oligopeptide segments: one non-fluorinated and one fluorinated. These oligopeptides were attached to the triblock copolymers by using thiol–ene ‘click’ chemistry. The modified polymers were coated onto treated glass slides and the surfaces were characterized using contact angle measurements. Near-edge X-ray absorption fine structure studies were used to show the delivery of oligopeptide segments to the film surface, even in cases when those surface groups were in competition with PDMS blocks. The coatings were tested for antifouling and fouling-release properties against sporelings of the green alga Ulva linza and cells of the diatom Navicula incerta. The modified PS-b-P(DMS-stat-VMS)-b-PS coatings performed well against the U. linza sporelings, and the PS-b-P(EO-stat-AGE)-b-PS coating performed well against both biofoulers.

Structural insights into the effect of cholinium-based ionic liquids on the critical micellization temperature of aqueous triblock copolymers

Symmetrical poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) triblock copolymer with 82.5% PEG as the hydrophilic end blocks, and PPG as the hydrophobic middle block, was chosen to study the effect of ionic liquids (ILs) on the critical micellization temperature (CMT) of block copolymers in aqueous solution. In the present work, cholinium-based ILs were chosen to explore the effect of the anions on the copolymer CMT using fluorescence spectroscopy, dynamic light scattering (DLS), viscosity (η), FT-IR spectroscopy, nuclear magnetic resonance (NMR), and direct visualization of the various self-assembled nanostructures by scanning electron microscopy (SEM). The result suggests that ILs have the ability to decrease the CMT of the aqueous copolymer solution which is dependent on the nature of the anions of the ILs. The present study reveals that the hydrophobic part PPG of the copolymer has more influence on this behavior than the PEG hydrophilic part.

Dependence of aggregation behavior on concentration in triblock copolymer solutions: The effect of chain architecture.

Using the self-consistent field lattice technique, the effects of concentration and hydrophobic middle block length (where the chain length remains constant) on aggregation behavior are studied in amphiphilic symmetric triblock copolymer solutions. The heat capacity peak for the unimer-micelle transition and the distribution peaks for the different degrees of aggregation for micelles and small aggregates (submicelles) are calculated. Analysis of the conducted computer simulations shows that the transition broadness dependence on concentration is determined by the hydrophobic middle block length, and this dependence is distinctly different when the length of the hydrophobic middle block changes. Different size for small aggregates simultaneously appear in the transition region. As temperature decreases, the number of different size small aggregates for the large hydrophobic middle block length first ascends and then descends in aggregation degree order. These results indicate that any transition broadness change with concentration is related to the mechanism of fragmentation and fusion. These results are helpful for interpreting the aggregation process of amphiphilic copolymers at equilibrium.

Coarse-Grained Simulation of Polycation/DNA-Like Complexes: Role of Neutral Block

Complexes formed by polycations and DNA are of great research interest because of their prospective application in gene therapy. Whereas the applications of multiblock based polycation generally exhibit promising features, a thorough understanding on the effect of neutral block incorporated in polycation is still lacking. By using coarse-grained dynamics simulation with the help of a simple model for solvent mediated interaction, we perform a theoretical study on the physicochemical properties of various polyplexes composed of a single DNA-like polyanion chain and numbers of linear polycationic chains with different modifications. By analyzing various properties, we find the hydrophobic/hydrophilic modifications of linear polycations may bring an improvement on one aspect of the properties as gene carrier but also involve a trade-off with another one. In particular, polycation with a hydrophobic middle block and a hydrophilic tail block display distinct advantages among di- and triblock linear polycations as gene carrier, while careful design of the hydrophobic block should be made to reduce the zeta potential. The simulation results are compared with available experimental data displaying good agreements.

Block Copolymer Micelles with a Dual-Stimuli-Responsive Core for Fast or Slow Degradation

We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.

Self‐assembly of ABA triblock copolymers based on functionalized polydimethylsiloxane and polymethyloxazoline

AbstractThis study describes the responsive behavior of modified amphiphilic ABA triblock copolymers of polymethyloxazoline‐block‐poly(methylhydrosiloxane‐co‐dimethylsiloxane)‐block‐polymethyloxazoline (PMOX‐b‐P(MHS‐co‐DMS)‐b‐PMOX) when subjected to compression on the water surface or to ions in the water bulk phase. The hydrophobic middle block was functionalized with spacers bearing methyl 2‐hydroxybenzoate (Bz) or 18‐crown‐6 ether (Ce) groups. The behavior at the air–water interface was studied by measuring surface pressure versus mean molecular area (π–mmA) isotherms, and atomic force microscopy (AFM) was employed to investigate the morphology of Langmuir–Blodgett (LB) films after transfer to solid supports. Ion‐responsive self‐assembly was followed using light microscopy and can be understood on a molecular level by employing 1H NMR spectroscopy. The π‐mmA isotherm of PMOX‐b‐P(MHS‐co‐DMS)‐b‐PMOX‐44Bz at the air–water interface had an extended pseudo‐plateau at a surface pressure of ca 22 mN m−1 reflecting the coil to loop transformation of the hydrophobic middle block which was absent for the crown ether‐functionalized triblock copolymer. AFM images of LB films of PMOX‐b‐P(MHS‐co‐DMS)‐b‐PMOX‐44Bz showed dewetting effects of the polymer film after transfer to a silicon wafer. LB films of PMOX‐b‐P(MHS‐co‐DMS)‐b‐PMOX‐8Ce formed surface micelles having a size of ca 50–100 nm on the solid support. The ion sensitivities of the crown ether‐derivatized copolymers in solution were investigated by exposing polymeric vesicles to potassium, sodium and magnesium ions. Exposure to K+ and Na+ led to vesicle rupture and the formation of micro‐tubular structures, while Mg2+ had no effect on the vesicular structures as confirmed using light microscopy. Specific interactions between the crown ether‐derivatized polymer and ions were further elucidated from 1H NMR experiments that indicated that K+ coordinated with the crown ether causing the dense packing to subside and leading to solubilization of the polymer in water. Copyright © 2010 Society of Chemical Industry

Cyclodextrin-based self-assembled supramolecular hydrogels and cationic polyrotaxanes for drug and gene delivery applications

The supramolecular self-assembly between cyclodextrins (CDs) and polymers has been used for the development of novel supramolecular hydrogels and polyrotaxanes for drug and gene delivery applications. So far, a lot of supramolecular hydrogels have been formed between CDs and poly(ethylene oxide) or its copolymers. The supramolecular hydrogels are thixotropic and reversible, and can be injected through a needle from a syringe to form injectable drug delivery systems. In order to develop supramolecular hydrogels with better controlled release properties, suitable for long-term controlled release of drugs, the supramolecular hydrogels were formed by α-CD and various triblock copolymers where PEO blocks flank a hydrophobic middle block and where the extra intermolecular hydrophobic interaction of the middle blocks can further strengthen the hydrogel network. This induces the formation of more stable hydrogels for long-term controlled release of drugs. New cationic polyrotaxanes composed of multiple oligoethylenimine-grafted CDs threaded and end-capped on a block copolymer chain were designed and synthesized as a new class of polymeric gene delivery vectors, where the chain-interlocked cationic cyclic units formed an integrated supramolecular entity to function as a macromolecular gene vector. These supramolecular gene carriers have low cytotoxicity, strong DNA-binding capability, and high gene transfection efficiency. The development of the supramolecular hydrogels and gene carriers based on the inclusion complexation between CDs and polymers has opened up a new approach for designing novel drug and gene delivery systems.

Fusion and fission pathways of vesicles from amphiphilic triblock copolymers: a dissipative particle dynamics simulation study

Dissipative particle dynamics (DPD) simulations are employed to study the fusion and fission dynamics of polymeric vesicles formed from amphiphilic triblock copolymers. The amphiphilic molecule is built from two hydrophilic blocks and a hydrophobic middle block. Two different pathways for both fusion and fission processes of two-component vesicles with polymer-based symmetric membranes have been found in the simulations. For each of the pathways, the conditions required to obtain complete fusion and fission have been investigated. Moreover, the fission process of single-component vesicles with polymer-based asymmetric membranes has also been studied in the simulations. Interestingly, the daughter vesicles have the same composition as the parent vesicle and only one fission pathway has been observed. Furthermore, the fusion and fission pathways have been compared and distinct vesicle recycling pathways have been suggested according to the results from the simulations. These findings may be helpful in explaining the fusion and fission dynamics of vesicles and understanding the general principle of membranes.

Effects of the Incorporation of a Hydrophobic Middle Block into a PEG−Polycation Diblock Copolymer on the Physicochemical and Cell Interaction Properties of the Polymer−DNA Complexes

One-component homopolymers of cationic monomers (polycations) and diblock copolymers comprising poly(ethylene glycol) (PEG) and a polycation block have been the most widely used types of polymers for the formulation of polymer-based gene delivery systems. In this study, we incorporate a hydrophobic middle block into the conventional PEG-polycation architecture and investigate the effects of this hydrophobic modification on the physicochemical and cell-level biological properties of the polymer-DNA complexes that are relevant to gene delivery applications. The ABC-type triblock copolymer used in this study consists of (A) PEG, (B) hydrophobic poly( n-butyl acrylate) (PnBA), and (C) cationic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) component polymers. The properties of the triblock copolymer/DNA complexes are compared with those of two other more conventional DNA carriers derived, respectively, using a PDMAEMA homopolymer and a PEG-PDMAEMA diblock copolymer that had comparable molecular weights for individual blocks. In aqueous solution, the PEG-PnBA-PDMAEMA polymer forms positively charged spherical micelles. The electrostatic complexation of these micelles with plasmid DNA molecules results in the formation of stable small-sized DNA particles that are coated with a micelle monolayer, as confirmed by agarose gel electrophoresis, dynamic light scattering (DLS), and cryogenic transmission electron microscopy (cryo-TEM). Proton nuclear magnetic resonance ( (1)H NMR) spectroscopy measurements indicate that the whole micelle-DNA assembly (named "micelleplex" for convenience) is shielded predominantly by the PEG chains. DLS and optical microscopy imaging measurements indicate that compared with PDMAEMA-DNA polyplexes, the micelleplexes have a significantly lower tendency to aggregate under physiological salt concentrations and show reduced interactions with negatively charged components in serum such as albumin and erythrocytes. While the micelleplexes are comparable to the PEG-PDMAEMA-based DNA polyplexes in terms of their stability against aggregation under high salt concentrations and in the presence of the albumin protein, they have a slightly higher tendency to interact with erythrocytes than the diblock copolymer polyplexes. Agarose gel electrophoresis measurements indicate that relative to the PEG-PDMAEMA polyplexes, the micelleplexes provide better protection of the encapsulated DNA from enzymatic degradation and also exhibit greater stability against disintegration induced by polyanionic additives; in these respects, the PDMAEMA homopolymer-based polyplexes show the best performance. In vitro studies in HeLa cells indicate that the PDMAEMA polyplexes show the highest gene transfection efficiency among the three different gene delivery systems. Between the micelleplexes and the PEG-PDMAEMA polyplexes, a higher gene transfection efficiency is observed with the latter system. All three formulations show comparable levels of cytotoxicity in HeLa cells.

RGD peptide grafted biodegradable amphiphilic triblock copolymer poly(glutamic acid)‐b‐poly(L‐lactide)‐b‐poly(glutamic acid): Synthesis and self‐assembly

AbstractA novel amphiphilic biodegradable triblock copolymer (PGL‐PLA‐PGL) with polylactide (PLA) as hydrophobic middle block and poly(glutamic acid) (PGL) as hydrophilic lateral blocks was successfully synthesized by ring‐opening polymerization (ROP) of L‐lactide (LA) and N‐carboxy anhydride (NCA) consecutively and by subsequent catalytic hydrogenation. The results of cell experiment of PGL‐PLA‐PGL suggested that PGL could improve biocompatibility of polyester obviously. The copolymer could form micelles of spindly shape easily in aqueous solution. The pendant carboxyl groups of the triblock copolymer were further activated with N‐hydroxysuccinimide and combined with a cell‐adhesive peptide GRGDSY. Incorporation of the oligopeptide further enhanced the hydrophilicity and led to formation of spherical micelles. PGL‐PLA‐PGL showed better cell adhesion and spreading ability than pure PLA and the GRGDSY‐containing copolymer exhibited even further improvement in cell adhesion and spreading ability, indicating that the copolymer could find a promising application in drug delivery or tissue engineering. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3218–3230, 2007

Salt induced micellization of very hydrophilic PEO–PPO–PEO block copolymers in aqueous solutions

Symmetrical poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide), PEO–PPO–PEO, triblock copolymers with 80% polyethylene oxide (PEO, the hydrophilic end blocks) and polypropylene oxide (PPO, the hydrophobic middle block) usually remain as molecularly dissolved at ambient temperature even at fairly high-concentrations (2 wt.% or more). However, the micellization is induced at lower concentration/temperature in the presence of salts. The results on salt induced micellization from four such hydrophilic copolymers Pluronic ® F38, F68, F88 and F108 obtained from several independent techniques are described. FTIR and fluorescence results provide essentially identical critical micelle temperatures (CMTs) showing marked decrease with increase in PPO molecular weight and in the presence of salt. These copolymers were weakly surface active and did not show a clear break point in surface tension concentration plot typical of surfactants. While addition of salt decreases the cloud point, no significant micelle growth was observed even at temperature close to cloud point (CP). Marked increased in solubilization of an oil dye was observed in presence of KCl. Different methods showed good agreement in temperature/salt-induced micellization of these hydrophilic copolymers.

Asymmetric Membranes from Amphiphilic ABC Triblock Copolymers

We report the synthesis and characterization of a new kind of amphiphilic ABC triblock copolymers consisting of a hydrophilic(polyethylene oxide)- A block a hydrophobic poly(dimethyl siloxane)-B middle block and a hydrophilic-poly(2-methyl oxazoline)C block. For certain hydrophilic to hydrophobic block length ratios these polymers self-assemble into membrane-like super-structures and vesicles in aqueous media. Due to the inherent incompatibility of the two hydrophilic blocks they segregate to different sides of the underlying membranes thus leading to asymmetric block copolymer membranes. Moreover, depending on the relative lengths of the two hydrophilic blocks we are able to control which of them is oriented toward the inner and the outer surface of the vesicles. Different water-soluble polymers are inherently incompatible and undergo phase separation in aqueous media. Hence, membranes formed by ABC triblock copolymers(with water soluble blocks A and C and a hydrophobic middle block B)are asymmetric: one side is predominantly covered by the blocks A and the other by the blocks B. These systems offer not only a convenient way to modify the inner and outer surface of vesicles with different functional groups but represent also an asymmetric matrix for the directed insertion of membrane proteins.

Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic ® (PEO–PPO–PEO) block copolymers

Pluronic ® block copolymers are commercially available symmetric triblock copolymers with poly(ethylene oxide), PEO, as the hydrophilic end blocks and poly(propylene oxide), PPO, as the hydrophobic middle block. In this paper, the solubilization of hydrocarbons by aggregates of Pluronic ® block copolymers in water is examined in the framework of a simple molecular theory of solubilization. The aggregates have an inner core region made up of PPO and the solubilizate and an outer corona region made up of PEO and water. Expressions for the standard state free energy change associated with solubilization of hydrocarbons by aggregates having spherical, cylindrical, and lamellar shapes are presented. These free energy contributions account for the mixing of the core block with the solubilizate, the consequent changes in the state of deformation of the core block, the changes in the state of dilution and deformation of the corona block, the formation of the core-solvent interface, and the backfolding of the triblock copolymer which ensures that the two end blocks are in contact with the solvent. Utilizing these free energy expressions, we predict the core size, the corona thickness, and the aggregation number of the micelle and also the volume fraction of the hydrocarbon solubilized in the core, for seven aromatic and aliphatic hydrocarbon solubilizates incorporated within numerous Pluronic ® compounds. The calculated results show that a growth in aggregate size occurs both because of the incorporation of the hydrocarbon and also the increase in the intrinsic number of block copolymer molecules per aggregate. More interestingly, solubilization is shown to induce a transition in aggregate shapes from spheres to cylinders and then to lamellae. The shape transition is found to be critically controlled by the free energy of mixing of the solubilizate with the core forming PPO block.