Amphiphilic Block Copolymer Poly Research Articles

A new drug carrier: Magnetite nanoparticles coated with amphiphilic block copolymer

This paper reports on the synthesis and characterization of 4 nm magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PEMA-b-PHEMA) by surface-initiated atom transfer radical polymerization (ATRP), which can act as new potential carriers for hydrophobic targeted drug delivery. Vibrating sample magnetometer analysis indicated that the magnetite nanoparticles were superparamagnetic at room temperature. Thermogravimetric analysis (TGA) was applied to studying the property of surface of magnetite nanoparticles, and the surface density of macromolecules was calculated. The grafting density of oleic acid, BrMPA and PEMA was 5.8, 3.9, 0.16 chain/nm2 respectively, which indicates that the initiation efficiency decreases due to the influence of large space of oleic acid molecules. In vitro progesterone and (−)-isoproterenol hydrochloride release in phosphate buffered saline (PBS) at pH 7.0 and 37°C was conducted in order to demonstrate the function of drug loading and release. The results showed that the amount of drug carried into the core-shell Fe3O4@PEMA-b-PHEMA depends on the length of hydrophobic segment of block copolymer. The release of progesterone (37% after 22 h in our previous work) was compared with the release of (−)-isoproterenol hydrochloride (80% after 50 min), demonstrating that the strong hydrophobic interaction between hydrophobic segment and drug can effectively control the release of hydrophobic drugs.

Synteza amfifilowych kopolimerow blokowych epsilon-kaprolaktonu typu ABA

Series of amphiphilic block copolymers of poly(e-caprolactone) (PCL) and poly(oxy)-ethylene glycol monomethyl ether (MPEG) of ABA type were synthesized in two-stage process. At first stage the isocyanate prepolymers (PCLpre) were prepared in the reactions of polyesterdiols (PCLdiol) of various molecular weights with either hexamethylene diisocyanate (HDI) or isophorone diisocyanate (IPDI) carried out in the presence of dibutyltin dilaurate (DBTL). PCLpre coupling with MPEG in the presence of the same catalyst was the other stage of synthesis. The products (PCLpre and MPEG--PCL-MPEG) were characterized by 1 H NMR, IR and DSC methods (Fig. 1-4, Table 1 and 2). It was found in solubility tests in water of triblock copolymers obtained that aggregates were formed in aqueous solutions (Fig. 5).

A novel route to in‐situ incorporation of silver nanoparticles into supramolecular hydrogel networks

AbstractA novel strategy was developed for the in situ incorporation of silver nanoparticles into the supramolecular hydrogel networks, in which colloidally stable silver hydrosols were firstly prepared in the presence of an amphiphilic block copolymer of poly(oxyethylene)‐poly(oxypropylene)‐poly(oxyethylene) and then mixed with aqueous solution of α‐cyclodextrin. The analyses from rheology, X‐ray diffraction, and scanning electron microscopy confirmed the formation of the supramolecular‐structured hydrogels hybridized with silver nanoparticles. In particular, the colloidal stability of the resultant silver hydrosol and its gelation kinetics in the presence of α‐cyclodextrin as well as the viscoelastic properties of the resultant hybrid hydrogel were investigated under various concentrations of the used block copolymer. It was found that the used block copolymer could act not only as the effective reducing and stabilizing agents for the preparation of the silver hydrosol but also as the effective guest molecule for the supramolecular self‐assembly with α‐cyclodextrin. In addition, the effects of silver nanoparticles on the gelation process and the hydrogel strength were also studied. Such a hybrid hydrogel material could show a good catalytic activity for the reduction of methylene blue dye by sodium borohydride. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 740–749, 2009

Ring-opening metathesis polymerization-derived, polymer-bound Cu-catalysts for click-chemistry and hydrosilylation reactions under micellar conditions

Ring-opening metathesis polymerization has been used for the synthesis of the amphiphilic block-copolymer poly(M1-co-M3)-b-poly(M2) from the hydrophilic monomer 5-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxymethyl}-7-oxabicyclo[2.2.1]hept-2-ene (M2), and the hydrophobic monomers endo,exo-5-decyloxymethyl-bicyclo[2.2.1]hept-2-ene (M1) and 1,3-di(1-mesityl)-4-{[(bicyclo[2.2.1]hept-5-en-2-ylcarbonyl)oxy]methyl}-4,5-dihydro-1H-imidazol-3-ium carboxylate (M3). Poly(M1-co-M3)-b-poly(M2) was loaded with Cu and the resulting Cu(I)-loaded polymer poly(M1-co-M3)-b-poly(M2)-Cu was used for a series of Cu-catalyzed reactions under micellar conditions, i.e. for the [3 + 2] cycloaddition of azides to alkynes and for carbonyl hydrosilylation reactions. Under such micellar conditions, the polymer-bound Cu-catalyst was found to be an efficient catalyst for all reactions investigated. Turn-over numbers (TONs) in cycloaddition reactions were in the range of 200-375, those in hydrosilylation reactions approximately 2000 allowing for Cu-loadings of 0.05 mol% with respect to substrate.

CMC and dynamic properties of poly(VA-b-St) copolymer micelles for drug delivery

The polymeric micelles from amphiphilic block copolymer poly(vinyl alcohol-b-styrene) (poly(VA-b-St)) with different syndiotacticity of poly(vinyl alcohol) (PVA) block were prepared by dialysis against water. Critical micelle concentration (CMC) and dynamic properties of poly(VA-b-St) copolymeric micelles were investigated by fluorescence techniques. From the fluorescence emission spectrum measurements using pyrene as a fluorescence probe, the observed CMC value was in the range of 0.125–4.47 mg/L. The CMC value increased with decreasing the weight ratio of PS to PVA block and with increasing the syndiotacticity of PVA block. The rate of pyrene release was very slow for block copolymers containing PVA block with higher syndiotacticity, which indicates that their micelles have increased kinetic stability.

Preparation of Shell Cross-Linked Thermoresponsive Micelles as well as Hollow Spheres Based on P(NIPAAm-co-HMAAm-co-MPMA)-b-PCL

A novel amphiphilic block copolymer poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate)-b-poly(e-caprolactone) (P(NIPAAm-co-HMAAm-co-MPMA)-b-PCL) bearing thermosensitivity as well as biodegradability was synthesized for the production of hollow spheres. A three-step approach was employed to prepare shell cross-linked (SCL), thermoresponsive hybrid hollow spheres: (1) micellization of P(NIPAAm-co-HMAAm-co-MPMA)-b-PCL, (2) cross-linking of the hydrophilic shell via acid-catalyzed sol−gel process, and then (3) degrading the PCL core with an enzyme. Transmission electron microscopy (TEM) studies and size measurements showed that the resultant hollow spheres exhibited regularly globular shape with diameter of around 170 nm. The structures of the SCL micelles and the hollow spheres were characterized by Fourier-transform infrared (FT-IR) measurements and laser light scattering (LLS) analyses. The SCL hollow spheres showed reversible dispersion/aggregation in respon...

PEO-Based Block Copolymers and Homopolymers as Reactive Surfactants for AGET ATRP of Butyl Acrylate in Miniemulsion

Amphiphilic block copolymers poly(ethylene oxide)-b-polystyrene (PEO-PS-Br) with various molecular weights and poly(ethylene oxide) homopolymer (PEO-Br) were synthesized and used as macroinitiators and stabilizers (reactive “surfactants”) for activator generated by electron transfer atom transfer radical polymerization (AGET ATRP) of n-butyl acrylate (BA), in miniemulsion either with or without ethyl 2-bromoisobutyrate (EBiB) as co-initiator. Under both conditions, the reactions were well controlled and stable latexes were formed. In the absence of EBiB, polymer particles with diameter around 120−230 nm were obtained, and the particles contained polymers with molecular weight Mn = 16 000−25 000 g/mol and relatively low polydispersity (Mw/Mn = 1.2−1.4). In the presence of a low molecular weight initiator, EBiB, the amount of surfactant used can be reduced in the reaction (1.7−4 wt % vs monomer). The percent of initiating sites from EBiB was changed from 30% to 90%, and the majority of the obtained polymers...

Investigation into the controlled release behavior of gemcitabine-loaded nanovesicles

To prepare gemcitabine-loaded nanovesicles and to observe its morphology, structure, particle size, and drug-release performance in vitro. Diemulsion technique was used to prepare nanovesicles as carrier from amphiphilic block copolymer of poly (ethylene glycol)-block-poly (D, L-lactide), and gemcitabine was used as the model drug. The morphology of vesicles was determined by scanning electron microscope (SEM) and transmission electron microscope (TEM), and its drug loading (DL), encapsulation ratio (ER), and drug-release curve in vitro were detected by UV-Vis-NIR Spectrophotometer. The Gemcitabine-loaded nanovesicles is a kind of hollow nanosphere with the mean size of 200.6 nm, DL of 4.14% and ER of 20.54%. The nanovesicles showed its excellent controlled-release characteristic in the experiment of drug release in vitro. The nanovesicles prepared from PEG-PDLLA can be served as one of carriers for Gemcitabine with good performance of drug controlled-release. It will provide a reliable experimental base for the further researches in vivo.

Preparation and self‐assembly behavior of thermosensitive polymeric micelles comprising poly(styrene‐b‐N,N‐diethylacrylamide)

AbstractThe amphiphilic block copolymer poly(styrene‐b‐N,N‐diethylacrylamide) (PSt‐b‐PDEA) was synthesized by reversible addition‐fragmentation chain transfer (RAFT) polymerization of styrene and N,N‐diethylacrylamide. The results of 1H‐NMR and GPC analysis showed that the synthesized PSt‐b‐PDEA copolymer had controlled molecular weight and narrow polydispersity. Polymeric micelles having a unimodal size distribution with an average diameter of 40 ± 0.5 nm were obtained from purified PSt‐b‐PDEA using a dialysis method. And the results showed that the clearance of homopolymer in copolymer is the key to prepare the unimodal distribution core‐shell nanomicelles. The micelles were thermodynamically stable in aqueous media with a low critical micelle concentration value (0.1 mg L−1). The aqueous micelles solution underwent a reversible dispersion/aggregation transition at around 29°C, which corresponds to the lower critical solution temperature (LCST) of the outer shell PDEA block chains. It is hoped that with their unique characteristics, those thermoresponsive polymeric micelles would found application in drug delivery. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Protein Conjugation with Amphiphilic Block Copolymers for Enhanced Cellular Delivery

Modification of a model protein, horseradish peroxidase (HRP), with amphiphilic block copolymer poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic), was previously shown to enhance the transport of this protein across the blood-brain barrier in vivo and brain microvessel endothelial cells in vitro. This work develops procedures for synthesis and characterization of HRP with Pluronic copolymers, having different lengths of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) blocks. Four monoamine Pluronic derivatives (L81, P85, L121, P123) were synthesized and successfully conjugated to a model protein, HRP, via biodegradable or nondegradable linkers (dithiobis(succinimidyl propionate) (DSP), dimethyl 3,3'-dithiobispropionimidate (DTBP), and disuccinimidyl propionate (DSS)). The conjugation was confirmed by HRP amino group titration, matrix-assisted laser desorption/ionization-time of flight spectroscopy, and cation-exchange chromatography. HRP conjugates containing an average of one to two Pluronic moieties and retaining in most cases over 70% of the activity were synthesized. Increased cellular uptake of these conjugates was demonstrated using the Mardin-Derby canine kidney cell line and primary bovine brain microvessel endothelial cells. The optimal modifications included Pluronic L81 and P85. These copolymers have shorter PPO chains compared to Pluronic P123 and L121, which were less efficient. There was little if any dependence of the uptake on the length of the hydrophilic PEO block for the optimal modifications. The proposed modifications may be used to increase cellular uptake of other proteins.

Aggregation and Self-Assembly of Amphiphilic Block Copolymers in Aqueous Dispersions of Carbon Nanotubes

The self-assembly (SA) of amphiphilic block copolymers (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)) was investigated in dispersions of single-walled and multiwalled carbon nanotubes (SWNT and MWNT, respectively) as a function of temperature. Differential scanning calorimetry (DSC) was used for characterization of the thermal behavior of the combined polymers-nanostructures system, and spin-probe electron paramagnetic resonance (EPR) was employed for probing the local dynamic and polarity of the polymer chains in the presence of nanostructures. It was found that SWNT and MWNT modify the temperature, enthalpy, and dynamic behavior of polymer SA. In particular, SWNT were found to increase the cooperativity of aggregating chains and dominate aggregate dynamics. MWNT reduced the cooperativity, while colloidal carbon black additives, studied for comparison, did not show similar effects. The experimental observations are consistent with the suggestion that dimensional matching between the characteristic radius of the solvated polymer chains and the dimensions of additives dominate polymer SA in the hybrid system.

Folate-functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs

Targeted delivery is a highly desirable strategy to improve the diagnostic imaging and therapeutic outcome because of enhanced efficacy and reduced toxicity. In the current research, anticancer drug doxorubicin (DOX) and contrast agent for magnetic resonance imaging (MRI), herein superparamagnetic ion oxide Fe(3)O(4) (SPIO), were accommodated in the core of micelles self-assembled from amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL) with a targeting ligand (folate) attached to the distal ends of PEG (Folate-PEG-PCL). The in vitro tumor cell targeting efficacy of these folate functionalized and DOX/SPIO-loaded micelles (Folate-SPIO-DOX-Micelles) was evaluated upon observing cellular uptake of micelles by human hepatic carcinoma cells (Bel 7402 cells) which overexpresses surface receptors for folic acid. In the Prussian blue staining experiments, cells incubated with Folate-SPIO-DOX-Micelles showed much higher intracellular iron density than the cells incubated with the folate-free SPIO-DOX-Micelles. According to the flow cytometry data, cellular DOX uptake observed for the folate targeting micelle was about 2.5 fold higher than that for the non-targeting group. Furthermore, MTT assay showed that Folate-SPIO-DOX-Micelles effectively inhibited cell proliferation, while the folate-free SPIO-DOX-Micelles did not show the same feat at comparable DOX concentrations. The potential of Folate-SPIO-DOX-Micelle as a novel MRI-visible nanomedicine platform was assessed with a 1.5 T clinical MRI scanner. The acquired MRI T (2) signal intensity of cells treated with the folate targeting micelles decreased significantly. By contrast, T (2) signal did not show obvious decrease for cells treated with the folate-free micelles. Our results indicate that the multifunctional polymeric micelles, Folate-SPIO-DOX-Micelles, have better targeting tropism to the hepatic carcinoma cells in vitro than their non-targeting counterparts, and the cell targeting events of micelles can be monitored using a clinical MRI scanner.

Hexagonal to cubic phase transition in the D2O-induced reverse micellar solution of a PEO-b-PPO-b-PEO block copolymer

The morphology of the D2O-induced reverse micellar structure of an amphiphilic block copolymer of poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide)(EO76PO29EO76) was investigated in hydrophobic media by small angle neutron scattering (SANS). Increasing D2O in the styrene/divinylbenzene solution of EO76PO29EO76 led to a change in morphology of the reverse micelles from a short range ordered molecular aggregate to a hexagonally arranged micelle, and further to a spherical micelle.

Metal-free synthesis of amphiphilic functional polycarbonates

Amphiphilic block copolymers of poly(5-benzyloxy trimethylene carbonate) (PBTMC) and poly(ethylene glycol) (PEG) were synthesized through enzymatic polymerization using immobilized porcine pancreas lipase (IPPL). The obtained copolymers with different compositions were characterized by GPC and 1H NMR. The copolymer composition was in agreement with the feed ratio. The molecular weight of the copolymers showed an increasing trend with the decrease of PEG contents. Micelles of the copolymers were formed by dialysis procedure, and characterized by transmission electron microscopy (TEM).

Block copolymer–oligonucleotide conjugates for genotyping on microarrays

Polymer–oligonucleotide conjugates were synthesized from the amphiphilic block copolymer poly( tert-butylacrylamide- b-( N-acryloylmorpholine- co- N-acryloxysuccinimide)) using an original solid-phase DNA synthesis strategy. This method provided conjugates highly functionalized with oligonucleotides throughout the polymer chain. After purification, block copolymer–oligonucleotide conjugates were spotted on a multidetection microarray system developed by Apibio using a standard nanodroplet piezo inkjet spotting technique to develop the oligosorbent assay (OLISA). Two genotyping models (HLA–DQB1 and platelet glycoproteins [GPs]), which are particularly difficult to study with standard systems, were evaluated. For both models, block copolymer–oligonucleotide conjugates used as capture probes amplified the responses of in vitro diagnostic assays. The detection limit reached by using conjugates was estimated at 15 pM for a 219-bp DNA target (HLA–DQB1 model). Moreover, single nucleotide polymorphism was detected in the platelet GPs genotyping model. The use of polymer conjugates led to a significant improvement in both sensitivity and specificity of standard hybridization assays even when applied to complex biological models.

Amphiphilic Poly(vinyl acetate)-b-poly(N-vinylpyrrolidone) and Novel Double Hydrophilic Poly(vinyl alcohol)-b-poly(N-vinylpyrrolidone) Block Copolymers Prepared by Cobalt-Mediated Radical Polymerization

Well-defined amphiphilic block copolymers of poly(vinyl acetate) (PVAc) and poly(N-vinylpyrrolidone) (PNVP) were synthesized by cobalt-mediated radical polymerization (CMRP). The NVP polymerization initiated by poly(vinyl acetate) end-capped by the cobalt(II)acetylacetonate complex met the criteria of controlled polymerization, i.e., first-order kinetic in NVP, increase of the molar mass with the NVP conversion, and narrow molar mass distribution. Therefore, the length of the two blocks can be tuned by the [VAc]/[Co(acac)2] and the [NVP]/[PVAc] ratios for the synthesis of the macroinitiator and the polymerization of the second monomer, respectively. These amphiphilic PVAc-b-PNVP block copolymers were easily converted into the double hydrophilic PVOH-b-PNVP counterparts by selective methanolysis of the PVAc block. These two types of copolymers were prone to self-association into micelles in appropriate solvents.

Self-assembling Behavior of Amphiphilic Copolymer Containing Cross-linked Hydrophilic Block in Ethanol

The self-assembly behavior of the amphiphilic block copolymer poly (methyl methacrylate)-block-poly (lead dimethacrylate) (PMMA-b-PLDMA) with cross-linked hydrophilic block (PLDMA) in ethanol was investigated. The results show that the size and morphology of the resulting micelle or micellar aggregates are ascribed to the content of ethanol and the nature of the solvent mixture. PbS nanoparticles were formed in the micelle by in situ reaction with H2S gas. The morphology and size of the self-assembly objects were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).

Preparation of Magnetite Nanoparticles Coated with an Amphiphilic Block Copolymer: A Potential Drug Carrier with a Core‐Shell‐Corona Structure for Hydrophobic Drug Delivery

AbstractSummary: The synthesis of magnetic magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)‐block‐poly(2‐hydroxyethyl methacrylate) for use as new potential carriers for hydrophobic drug delivery is reported. The results show that a new core‐shell‐corona structural material is obtained with a very narrow molecular weight distribution of the hydrophobic segment (PDI = 1.10). UV‐Vis results show that 37% of progesterone is released from the nanoparticles after 22 h, much slower than free release (99% after 14 h), which demonstrates that the presence of the hydrophobic segment can effectively control the release of hydrophobic drugs.Synthesis of an amphiphilic block polymer poly(ethyl methacrylate)‐block‐poly(2‐hydroxyethyl methacrylate) on magnetite nanoparticles and their use as potential drug carriersmagnified imageSynthesis of an amphiphilic block polymer poly(ethyl methacrylate)‐block‐poly(2‐hydroxyethyl methacrylate) on magnetite nanoparticles and their use as potential drug carriers

Preparation and properties of immobilized pectinase onto the amphiphilic PS-b-PAA diblock copolymers

Well-defined amphiphilic block copolymers poly(styrene-b-acrylic acid) (PS-b-PAA) with controlled block length were synthesized using atom transfer radical polymerization (ATRP). Pectinase enzyme was immobilized on the well-defined amphiphilic block copolymers PS-b-PAA. The carboxyl groups on the amphiphilic PS-b-PAA diblock copolymers present a very simple, mild, and time-saving process for enzyme immobilization. Various characteristics of immobilized pectinase such as the pH and temperature stability, thermal stability, and storage stability were valuated. Among them the pH optimum and temperature optimum of free and immobilized pectinase were found to be pH 6.0 and 65 degrees C.

Equilibrium exchange kinetics in PEP–PEO block copolymer micelles. A time resolved SANS study

The chain exchange kinetics in polymeric micelles has been studied by a novel time resolved small angle neutron scattering (TR-SANS) technique. The system investigated was the amphiphilic block copolymer poly(ethylene-alt-propylene)–poly(ethylene oxide) (PEP–PEO) in water / N , N -dimethylformamide (DMF) mixtures as selective solvent for PEO. The TR-SANS technique exploits the large difference in scattering length density of deuterated and protonated species allowing for a detailed study of chain exchange kinetics with virtually no perturbation from equilibrium. The measured relaxation curves show a fast initial decay which gradually slows down at longer times. This extremely broad and heterogeneous decay drastically deviates from single exponential predicted by the scaling theory of Halperin and Alexander. Instead, the data appear to follow a logarithmic time dependence. This behavior most likely stems from a heterogeneous release of core chains caused by strong topological correlations inside the small micellar cores.