Interaction between zero-charged catanionic vesicles and PEO–PPO–PEO triblock copolymers

We investigate the interaction between zero-charged catanionic vesicles and PEO–PPO–PEO (poly(ethylene oxide–poly(propylene oxide)–poly(ethylene oxide)) triblock copolymers. The 25-mg mL^?1 aqueous solution of tetradecyltrimethylammonium laurate (TTAL) contains closely packed uni- and multi-lamellar vesicles and shows viscoelastic properties with a dominant elastic modulus (G′) over a viscous modulus (G″). When a small amount of F127 ((EO)₉₇(PO)₆₉(EO)₉₇) or F68 ((EO)₇₆(PO)₂₉(EO)₇₆) was added, an improvement of the viscoelasticity was observed at suitable polymer concentrations. Freeze–fracture transmission electron microscopy (FF-TEM) observations on an F68-containing system revealed interesting aggregate transition from vesicles to flexible tubules and back to vesicles. The improvement of the viscoelasticity of the vesicular solution containing F68 or F127 can be explained by the formation of tubule and polymer–vesicle associates, while no such phenomenon was noticed for P123 ((EO)₁₉(PO)₆₉(EO)₁₉) which has the highest propylene oxide (PO) content and the strongest ability to self-associate in aqueous solution. In all the cases, vesicles will be destroyed and phase separation can be observed at high polymer contents (>5-mg mL^?1).     

Reduction of micellar size of PEO−PPO−PEO triblock copolymer in presence of ionic liquid in aqueous solutions: A SANS study

The interaction of ionic liquids (ILs) with non-ionic triblock copolymer, Pluronic® P123, in aqueous solutions has been investigated using Small Angle Neutron Scattering (SANS) measurements. The micellar structural parameters are obtained by fitting the SANS scattering data with model composed of core-shell form factor and a hard sphere structure factor of interaction, as a function of cationic head group of ILs. With the addition of ILs, a decrease in the micellar core, aggregation number, and hard sphere radius of P123 micelles was noticed. The results are discussed and explained as a function of cationic head groups of N-octylpyridinium/imidazolium chloride.     

Fabrication of organic–inorganic nano-complexes using ABC type triblock copolymer and polyoxotungstates

New organic–inorganic nano-complexes were produced from a micelle of tri-block polymers; poly(styrene)-b-poly(2-vinylpyridine)- b-poly (ethylene oxide) (PS-PVP-PEO) and tungsten compounds such as tungstate (W₁²⁻), undecatungstophospate (PW₁₁⁷⁻) and undecatungstosilicate (SiW₁₁⁸⁻) in acidic aqueous solutions. The size and morphology of the complexes were characterized by measurements of dynamic light scattering, atomic force microscopy, and scanning electron microscopy. This complex is assembled mainly by the charge interaction between the inorganic polyanions and the positively charged PVP block in the PS-PVP-PEO molecule, which was confirmed by zeta-potential and fluorescence spectroscopic studies. In the absence of the inorganic anions, the zeta-potential of the micelle was +11 mV at pH 3 due to the positive charge of the PVP block. When the inorganic anion was mixed with the PS-PVP-PEO micelle, decrease in the zeta-potential due to charge neutralization occurred with incorporation of inorganic anions into the PS-PVP-PEO micelle. The minimum zeta-potential was 0, −33, and −35 mV for W₁²⁻ /PS-PVP-PEO, PW₁₁⁷⁻ /PS-PVP-PEO, and SiW₁₁⁸⁻ /PS-PVP-PEO complexes, respectively. Excess negative charge which occurred in the latter two complexes indicates that PS-PVP-PEO molecules bound PW₁₁⁷⁻ and SiW₁₁⁸⁻ by forces other than charge interaction. In addition, the incorporation of an inorganic polyanion into the micelle gave a new morphology to the micelle. In the absence of the polyanion, the PS-PVP-PEO micelles showed an extended conformation due to repulsive forces working among the positively charged PVP blocks. Addition of the polyanion caused the formation of shrunken forms of the micelles, since the charge repulsion was cancelled by the polyanion. This feature may be useful in developing a new type of functioning micelle.     

Sustained release drug delivery using supramolecular hydrogels of the triblock copolymer PCL–PEG–PCL and α-cyclodextrin

Supramolecular hydrogels (SMGel) have attracted much attention as a drug and gene delivery system in recent years. In this study, SMGels based on the tri-block copolymer of poly-ε-caprolactone–polyethylene glycol–poly-ε-caprolactone (PCL–PEG–PCL) and α-cyclodextrin (α-CD) were prepared and evaluated for the delivery of two model drugs, naltrexone hydrochloride and vitamin B₁₂. Tri-block copolymers were synthesized easily in 15 min by ring-opening polymerization using the microwave irradiation technique, and their structures were determined by gel permeation chromatography and nuclear magnetic resonance methods. SMGels composed of various concentrations of the copolymer and α-CD were prepared and characterized for their rheological behaviour, their gel formation time and in vitro drug release profile. The results indicated that copolymers with a PCL to PEG ratio of 1:4 are suitable for SMGel preparation. The most viscose system with good syringeability was prepared by mixing 12 % wt α-CD and 10 % wt of copolymer. The gelation was found to occur within a minute after mixing. The viscosity of the hydrogel systems was determined as a function of shear rate. Finally, in vitro B₁₂ release through the hydrogel systems was studied. Up to 80 % of Vitamin B₁₂ was released through this system during a period of 20 days. Rheological evaluation revealed that the hydrogel has shear thinning properties, and the system regained its ground rheological state in a time dependent manner. Polymer concentration did not affect the drug release profiles. Finally, it was concluded that such systems are appropriate drug delivery systems due to their ability to provide a controlled drug release profile and their shear thinning thixotropic behaviour, which makes them syringeable and injectable.     

Solubilization and Release of a Model Drug Nimesulide from PEO–PPO–PEO Block Copolymer Core–Shell Micelles: Effect of Size of PEO Blocks

The commercially available polypropylene oxide (PPO)–polyethylene oxide (PEO) symmetrical triblock copolymers (Pluronics^®) have been recognized as pharmaceutical excipients and used in a variety of applications. This paper reports studies on micellar and solubilization behavior of three PEO–PPO–PEO block copolymers, viz. P103, P104 and P105 (same PPO mol. wt = 3250 g·mol^?1 but different  % PEO = 30, 40 and 50 %, respectively) in aqueous solutions. Critical micellization concentrations (CMCs), critical micellization temperatures (CMTs), and micelle size/polydispersity for copolymers with and without the drug, nimesulide (NIM), are reported. The solubilization of NIM is significantly enhanced with increasing hydrophobicity (P103 > P104 > P105), concentration, temperature and in the presence of added salt. The copolymer hydrophobicity, temperature and the drug loading strongly affect micelle behavior. The micelle–water partition coefficient (P) and thermodynamic parameters of solubilization, viz. Gibbs energy ( $ \Updelta G_{s}^{\text{o}} $ ), enthalpy ( $ \Updelta H_{s}^{\text{o}} $ ) and entropy ( $ T\Updelta S_{s}^{\text{o}} $ ), were calculated. The solubilization site of the drug in different micellar solutions and its release from Pluronics^® micelles in phosphate buffer saline (PBS) solution at 37 °C were examined. The kinetics of NIM exhibits burst release characteristics, which are believed to be controlled by degradation of the copolymers. These studies were carried out to investigate the feasibility of using Pluronics^® as a release vehicle of nimesulide in vitro. From the results, it was concluded that Pluronic^® based formulations might be practical for drug delivery.     

Controlling the properties of poly(amino ester urethane)–poly(ethylene glycol)–poly(amino ester urethane) triblock copolymer pH/temperature-sensitive hydrogel

A series of triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) was synthesized and characterized. Its aqueous solution can be used as a non-cytotoxic, biodegradable, and pH/temperature-sensitive hydrogel system. The copolymer solutions exhibited sol-to-gel and gel-to-sol transitions with increasing pH and temperature, respectively. The properties of this hydrogel system, such as its sol–gel transition diagram, mechanical properties, and degradation rate, can be controlled by modulating the PEG molecular weight, PAEU block length, copolymer concentration, or structure of the monomers. The presence of urethane groups and ionized tertiary amine groups in the copolymer solution at lightly acidic pH may lead to a strong interaction of the copolymer with formulated bioactive therapeutic agents, while the existence of the gel state under physiological conditions (37 °C, pH 7.4) may enable this copolymer hydrogel to be applicable as a drug/protein carrier.     

PEO–PPO based star-block copolymer T904 as pH responsive nanocarriers for quercetin: Solubilization and release study

Solubilization of quercetin (QN), a hypolipidemic drug in aqueous micellar solution of a star-like octablock Tetronic® T904 covering different salt concentration, pH and temperature is investigated. The change in pH modulates the charge of the copolymer which alters the dibasic nature of the centrally located ethylenediamine moiety and makes T904 undergo deprotonation favoring self assembly. At low pH, the columbic repulsion among the positively charged amine groups of Tetronic® hinders micellization while presence of salt facilitates it. The drug solubility data for micelles in aqueous/salt solutions determined by UV–Visible spectroscopy and micellar size with loaded drug from dynamic light scattering (DLS) are reported. Hydrophobic/anionic QN, deprotonates T904 and induces the micellization in acidic pH thus assisting solubilization. The expected locus (site) of the QN in T904 micelles was successfully correlated by the significant and positive cross peaks obtained from two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY). The evaluated in vitro release profile employing different kinetic models explains the controlled release of drug from T904 micelles.     

Tuning the morphology of amphiphilic copolymer aggregates by compound emulsifier via emulsion–solvent evaporation

A series of poly(4-vinylpyridine)-b-poly{6-[4-(4-butyloxyphenylazo)phenoxy]hexyl methacrylate} (P4VP-b-PAzoMA) were employed to fabricate aggregates via the emulsion–solvent evaporation method. The emulsion was stabilized by compound emulsifier composed of SDS and span60. By tuning the ratio of two emulsifiers, P4VP-b-PAzoMA could self-assemble into various morphologies including porous microspheres, tremella-like aggregates, bowl-like aggregates and wrinkled microspheres. The transformation of the morphologies could be ascribed to three major aspects: the stability of emulsified chloroform droplets, the permeation of water into chloroform and the dispersity of the interior water droplets with regard to different HLB values. Besides, the morphology could even be tuned by changing the block ratio and the concentration of P4VP-b-PAzoMA, and the HLB dependent morphology changing was also proved within other block ratio or different concentration. The study uncovers a convenient and effective technique to manipulate the morphology of amphiphilic copolymer aggregates.     

Morphology of poly(lactide)-block-poly(dimethylsiloxane)-block-polylactide high-χ triblock copolymer film studied by grazing incidence small-angle X-ray scattering

The morphologies of poly(lactide)-block-poly(dimethylsiloxane)-block-polylactide (PLA-b-PDMS-b-PLA) triblock copolymer films were studied using a combination of grazing-incidence small-angle X-ray scattering, X-ray reflectivity and scanning electron microscopy. This block copolymer is characterized by a high Flory–Huggins interaction parameter which leads to the self-assembly of periodic high-resolution nanodomains. In this article, we performed a detailed analysis of GISAXS patterns, in the frame of the Distorted Wave Born Approximation, in order to determine the morphology of blocks and their spatial arrangement. For a low volume fraction of PLA (17%), a three-dimensional hexagonal lattice of PLA spherical blocks is revealed, while, for a PLA fraction twice larger, in-plane (parallel) PLA lying cylinders adopt a two-dimensional centered rectangular lattice. Moreover, the in-depth electron density profile of the polymer film for the cylindrical morphology was extracted from the XRR data, revealing the presence of interfacial layers at the top surface and at the interface with the Si substrate.     

Studies of thermal properties of di(methacryloyloxymethyl)naphthalene–divinylbenzene (DMN–DVB) copolymer and its alkyl-bonded derivatives

This paper presents the thermal properties of highly crosslinked di(methacryloyloxymethyl)naphthalene–divinylbenzene (DMN–DVB) copolymeric microspheres containing polar groups in the structure and their alkyl-bonded derivatives. C₈ and C₁₈ alkyl chains were introduced into the aromatic rings of the DMN–DVB porous copolymer by means of the Friedel–Crafts reaction. As a source of C₈ and C₁₈ alkyl chains, octyl and octadecyl chlorides were used. It was necessary to check whether the introduction of alkyl chains into the structure of polymeric packing had an impact on its thermal properties. The studies were carried out by thermogravimetry coupled online with FTIR spectroscopy and differential scanning calorimetry in inert atmosphere (helium). It was stated that the modified materials showed 20 and 50% mass losses at higher temperatures than the non-modified one while 1% mass loss was observed at lower temperatures. Moreover, an analysis of volatile decomposition products was performed.

     

Quantitative determination of cationic modified polysaccharides on hair using LC–MS and LC–MS–MS

Cationic polysaccharides containing N-hydroxypropyl-N,N,N-trimethylammonium substituents are widely used as conditioning agents for hair-care products. A sensitive method has been developed for the quantitation of these polymers. After acidic extraction from hair the polysaccharides are hydrolyzed using trifluoroacetic acid. The cationic monoglycosides are determined using liquid chromatography–tandem mass spectrometry (LC–MS–MS). The developed method is independent of hair treatment. Even hair cut from test persons after customary hair wash can be analyzed. After treatment of natural and bleached hair tresses using a real-life treatment procedure 180 g and 300 g of polymer per gram hair were quantified, respectively. Additionally the fragmentation mechanism of the cationic N-hydroxypropyl-N,N,N-trimethylammonium group during electrospray ionization was investigated. A mass loss of 60 Da in combination with loss of a single charge is observed and associated with cleavage of trimethylamine and a proton. It is assumed that this process is promoted by the anionic counter-ion which might be hydroxide in an aqueous environment.     

Poly(ε-caprolactone)-block-poly(ethyleneoxide) -block-poly(ε-caprolactone): Biodegradable triblock copolymer spread at the air-water interface

Synthesis, characterization and behavior at the air-water interface of A-B-A triblock copolymers are reported. The copolymers consist of a poly(ethylene oxide) central block and poly(ε-caprolactone) lateral blocks. The synthesis was controlled in order to obtain central and lateral blocks of variable length. Copolymer characterization was performed by FTIR and ¹H NMR spectroscopy, size exclusion chromatography (SEC), and thermal analysis. Monolayers of the copolymers at the air-water interface were obtained by the Langmuir technique and the respective isotherms were obtained by monolayer compression. The limiting area per repeat unit (A_o) and the critical exponent of the excluded volume (ν) for spread monolayers were obtained. The static elasticity (ε₀) of the monolayers was also determined. The obtained results allow proposing a schematic model of the orientation of the different blocks during the compression of the respective monolayers.     

Biodegradable star-shaped poly(ethylene glycol)-poly(β-amino ester) cationic pH/temperature-sensitive copolymer hydrogels

Biodegradable star-shaped copolymers comprised of four-arm poly(ethylene glycol) (4-arm PEG) and poly(β-amino ester) (PAE) were synthesized by conjugating PAE to 4-arm PEG. The synthesized copolymers were characterized by ¹H and ¹³C NMR and gel permeation chromatography. The PAE showed pH/temperature-sensitive properties in an aqueous solution. The copolymer solutions (30 wt.%) showed a gel-to-sol phase transition as a function of temperature in the pH range 7.2–7.8. The gel window covers the physiological conditions (37 °C and pH 7.4) and can be controlled by varying the PAE block length, copolymer solution concentration and PEG molecular weight. After a subcutaneous injection of the copolymer solution into a SD rat, a gel formed rapidly in situ which remained for more than 2 weeks in the body. This copolymer is expected to be a potential candidate for biomedical applications.     

Soluble–insoluble polyelectrolyte complex of quaternized chitosan with DIVEMA (pyran copolymer)

To endow chitosan with solubility in the whole pH-range without loss of functionality of the amino groups, the cationic polysaccharide was exhaustively alkylated yielding N-[(2-hydroxy-3-trimethylammonium) propyl]chitosan chloride (QCht). Each alkylated unit of QCht contained both quaternary amino group and secondary amino group. Recently we demonstrated that QCht forms with nucleic acids of soluble polyelectrolyte complexes stable at physiological conditions and capable of cell transfection in vitro. In the current work, the anionic counterpart of QCht was hydrolyzed copolymer of divinyl ether and maleic anhydride (DIVEMA) which is known to possess some anti-tumor and immune stimulating activity and use as a drug carrier in anti-tumor drug delivery systems. According to the potentiometry data and ζ-potential measurements, almost all carboxylic groups of DIVEMA were able to form ion pairs with QCht. In aqueous and water–salt solutions, formation of either soluble or insoluble complexes was controlled by pH, ionic strength, a ratio of the oppositely charged groups, and degree of polymerization of the chains following general rules revealed on studying polyelectrolyte complexes of polycarboxylic acids. These findings evidence plausible advantages of the complex formation as the non-covalent modification that imparts to both polyelectrolytes of the ability for reversible soluble–insoluble transformation under enzyme-friendly conditions.     

Solubility of naphthalene in aqueous solutions of poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) triblock copolymers and (2-hydroxypropyl)cyclodextrins

The solubility of naphthalene was investigated in aqueous solutions of triblock copolymers poly(ethylene glycol)–poly(propylene glycol)–poly(ethylene glycol) (PEG–PPG–PEG) and (2-hydroxypropyl)cyclodextrins. The results with solutions of the individual solubilizers were as expected: the solubility enhancement was much higher with a micelle-forming copolymer than with the non-micellizing one and with (2-hydroxypropyl)--cyclodextrin (HPBCD) than with (2-hydroxypropyl)--cyclodextrin (HPACD). Although the formation of inclusion complexes between HPACD and PEG and between HPBCD and PPG is well established, the naphthalene solubility in mixed solutions does not significantly deviate from that predicted for a mixture of independent solubilizers. Thus the interactions between HPCD and PEG–PPG–PEG copolymers are not strong enough to disrupt micelles and aggregates formed by those copolymers. In fact, slight synergetic deviations were observed with the micellizing copolymer, indicating the existence of ternary naphthalene/HPCD/copolymer interactions. For pharmaceutical applications, it is important that the solubilization efficacy of PEG–PPG–PEG copolymers and that of cyclodextrins modified by the 2-hydroxypropyl group would not be compromised if these two types of solubilizers were co-administered.     

Features of the molecular–topological structure of γ-irradiated powdered tetrafluoroethylene–perfluoro(propyl vinyl ether) copolymer

With the use of thermomechanical spectrometry in two modes, coaxial, when the load application vector is coplanar with the compacting pressure vector (semicrystalline copolymer) during the measurement of the deformation of a copolymer of tetrafluoroethylene with perfluoro(propyl vinyl ether), and mutually perpendicular (completely amorphous copolymer), it has been established that the axial compression of the copolymer brought its topological structure to an absolutely anisotropic state. After γ-irradiation, the semicrystalline structure of the copolymer was retained regardless of the radiation dose. The minimum values of the glass transition temperature of the amorphous block and the degree of crystallinity were observed in the copolymer irradiated to a dose of 150 kGy. The molecular weight distribution functions of interjunction chains in the networks of the amorphous blocks of the initial copolymer and its γ-irradiated analogs are bimodal.     

Electrochemical detection of benzo(a)pyrene and related DNA damage using DNA/hemin/nafion–graphene biosensor

A novel electrochemical biosensor, DNA/hemin/nafion–graphene/GCE, was constructed for the analysis of the benzo(a)pyrene PAH, which can produce DNA damage induced by a benzo(a)pyrene (BaP) enzyme-catalytic product. This biosensor was assembled layer-by-layer, and was characterized with the use of cyclic voltammetry, electrochemical impedance spectroscopy (EIS) and atomic force microscopy. Ultimately, it was demonstrated that the hemin/nafion–graphene/GCE was a viable platform for the immobilization of DNA. This DNA biosensor was treated separately in benzo(a)pyrene, hydrogen peroxide (H₂O₂) and in their mixture, respectively, and differential pulse voltammetry (DPV) analysis showed that an oxidation peak was apparent after the electrode was immersed in H₂O₂. Such experiments indicated that in the presence of H₂O₂, hemin could mimic cytochrome P450 to metabolize benzo(a)pyrene, and a voltammogram of its metabolite was recorded. The DNA damage induced by this metabolite was also detected by electrochemical impedance and ultraviolet spectroscopy. Finally, a novel, indirect DPV analytical method for BaP in aqueous solution was developed based on the linear metabolite versus BaP concentration plot; this method provided a new, indirect, quantitative estimate of DNA damage.     

Binuclear cationic μ-bromo complexes of vanadium(II)

The compounds [V₂(μ-Br)₃L₆]BPh₄, with L = 3-methyltetrahydrofuran (1) and tetrahydrofuran (2), have been prepared. The crystal and molecular structures of 1 have been determined. The compound crystallizes in space group Cc with unit cell dimensions a = 18.499(3), b = 10.923(3), c = 29.619(7) Å, β = 103.18(2)^o, V = 5827(5) ų and Z = 4. The [V₂(μ-Br)₃(CH₃C₄H₇O)₆]⁺ ion is analogous to the [V₂(μ-Cl)₃L₆]⁺ cations previously described, but has a longer V—V distance, viz. 3.146(4) A. The UV-vis spectrum shows a double spin-flip transition but it is extremely weak compared to that in the chloro analog. Qualitatively, this was expected because of the ca 0.16 Å increase in the V—V distance, but the magnitude of the decrease (∼ 5 fold) is of interest.