ATRP synthesis and association properties of temperature responsive dextran copolymers grafted with poly(N-isopropylacrylamide)

Temperature responsive copolymers of dextran grafted with poly(N-isopropylacrylamide) (Dex-g-PNIPAAM) were prepared by atom transfer radical polymerization (ATRP) in homogeneous mild conditions without using protecting group chemistry. Dextran macroinitiator was synthesized by reaction of dextran with 2-chloropropionyl chloride at room temperature in DMF containing 2% LiCl. ATRP was carried out in DMF:water 50:50 (v/v) mixtures at room temperature with CuBr/Tris(2-dimethylaminoethyl)amine (Me₆TREN) as catalyst. Several grafted copolymers with well defined number and length of low polydispersity grafted chains were prepared. Temperature induced association properties in aqueous solution were studied as a function of temperature and polymer concentration by dynamic light scattering, fluorescence spectroscopy and atomic force microscopy (AFM). LCST, ranging from 35 to 41 °C, was significantly affected by number and length of grafted chains. The fine tuning of LCST around body temperature is an important characteristic not obtainable by conventional radical grafting of PNIPAAM. Well defined spherical nanoparticles were formed above the LCST of PNIPAAM. Hydrodynamic diameter was in the range 73-98 nm.     

Production of nanoparticles of methyl methacrylate and butyl methacrylate copolymers by microemulsion polymerization in the presence of maleic acid terminated poly(N-acetylethylenimine) macromonomers as cosurfactant

In this study, MMA/BMA copolymer nanoparticles were synthesized in oil-in-water microemulsions that were stabilized by sodium dodecyl sulphate (SDS) and initiated by potassium persulphate KPS. Maleic acid terminated poly(N-acetylethylenimine) (PNAEI) with two different chain lengths was also included in the recipe, as a cosurfactant and a comonomer. FTIR and ¹H-NMR proved incorporation of the macromonomer in the structure. High polymerization yields were achieved upto 98%. The viscosity average molecular weights of the copolymers were in the range of 2.77-5.50 × 10⁵. The glass transition temperatures of these copolymers were between 50.0 and 63.9 °C. The average diameter of nanoparticles were in range of 40-96 nm. It was possible to produce nanoparticles smaller than 100 nm and with narrower size distributions by using much lower concentrations of SDS by including the macromonomers in the microemulsion polymerization recipe.     

Statistical design strategies to optimize properties in miniemulsion polymerization of methyl methacrylate

PMMA particles were synthesized by a miniemulsion polymerization method using hexadecane as costabilizer and sodium dodecyl sulfate as surfactant. Full factorial experimental design incorporating the linear regression analysis of the experimental values was used to illustrate the usefulness of this technique in miniemulsion polymerization studies. The effect of initiator concentration, costabilizer concentration, surfactant concentration, sonication time and amplitude, and their interactions on the particle size were identified. Costabilizer and surfactant concentrations influence both particle size individually whereas initiator concentration influences particle size via its interactions with the costabilizer and the surfactant. Sonication parameters influence also greatly the particle size. Two mathematical models were established, and have demonstrated the capability of predicting particle diameter from the synthesis conditions with a precision of 1-2 nm over a range from 75 to 180 nm.     

Nanocomposite particles with core-shell morphology II. An investigation into the affecting parameters on preparation of Fe3O4-poly (butyl acrylate-styrene) particles via miniemulsion polymerization

The encapsulation of inorganic particles with polymers is desirable for many applications in order to improve the stability of the encapsulated products and disperse ability in different media. Colloidal particles with magnetic properties have become increasingly important both technologically and for fundamental studies. This is due to their tunable anisotropic. In the absence of an applied magnetic field, the particles have isotropic sphere dispersion, whereas in an external magnetic field the particles form anisotropic structures. Here, latexes containing nanocomposite particles of styrene-butyl acrylate/Fe₃O₄ with core-shell structure were prepared through miniemulsion polymerization technique. Magnetic composite nanospheres with high magnetic content were synthesized through miniemulsion polymerization using a new process based on a three-steps preparation route including two miniemulsion processes: (1) preparing a dispersion of oleic acid coated magnetite particles in water; (2) mixing of modified magnetite particles with styrene/butyl acrylate in the presence of sodium dodecyl sulfate (SDS), sorbitane mono oleate (Span 80), hexadecane (HD) and (3) miniemulsification of the modified Fe₃O₄ into the monomer droplets to reach to complete encapsulation. Subsequent polymerization generated magnetic nanocomposite spheres. Hence, the copolymerization reaction was performed on the surface of such particles in order to obtain core-shell morphology for these nanoparticles, which were characterized by several techniques such as TEM, SEM, DLS, TGA, VSM and FT-IR. The magnetic copolymer particles with diameter of 120-170 nm were obtained. The effect of several parameters such as magnetite, surfactants and hydrophobe amounts on the stability, particle size and magnetization were investigated and also optimized.     

In vitro ageing and degradation of PEG-PLA diblock copolymer-based nanoparticles

Diblock copolymers composed of poly(oxy-ethylene) (POE) and poly(dl-lactic acid) segments were synthesized by anionic polymerization of d,l-lactide using the oxyanion formed by reaction of the monohydroxyl monomethoxy-poly(ethylene glycol) on sodium hydride. For comparison, a similar copolymer was prepared by using tin octoate to catalyze the lactide polymerization. The copolymers were used to make nanoparticles, which were stored at 4 °C. After a few months under these storage conditions, a dramatic decrease of the poly(ethylene glycol) content was observed, however, the mean diameter of the nanoparticles was not affected. The degradation of the nanoparticles was investigated in vitro under conditions selected to mimic physiological conditions. Changes of characteristics were monitored by ¹H NMR, SEC, DLLS and CZE on nanoparticles and/or on the degradation by-products dissolved in the ageing medium. According to their nanometric dimensions, the microparticles degraded very slowly and there was no difference in behaviour between the sodium hydride and the stannous octoate-derived copolymers.     

Preparation and drug release property of CO2 stimulus-sensitive poly(N, N-dimethylaminoethyl methacrylate)-b-polystyrene nanoparticles

The CO₂ stimulus-sensitive nanoparticles based on poly(N, N-dimethylaminoethyl methacrylate)-b-poly styrene (PDMAEMA-b-PS) were prepared via surfactant-free miniemulsion reversible addition–fragmentation chain transfer (RAFT) polymerization. The as-prepared nanoparticles exhibited core–shell structure with about 120 nm in diameter. Their dispersion/aggregation in water can be adjusted by alternatively bubbling of CO₂ and N₂. Drug release from these nanoparticles can be accelerated (or delayed) by bubbling (or removing) of CO₂.     

Synthesis and characterization of polychloromethylstyrene nanoparticles of narrow size distribution by emulsion and miniemulsion polymerization processes

Polychloromethylstyrene nanoparticles of sizes from 12.0 ± 2.3 to 229.6 ± 65 nm were prepared by the emulsion and miniemulsion polymerization of chloromethylstyrene in an aqueous continuous phase in the presence of potassium persulfate as initiator, sodium octylbenzenesulfonate as surfactant, and hexadecane as costabilizer for the miniemulsion polymerization process only. The influence of various polymerization parameters (e.g., concentration of the monomer, initiator, the crosslinker monomer, and the surfactant) on the properties of the particles (e.g., size, size distribution, and yield) has been elucidated. The polychloromethylstyrene nanoparticles formed via the emulsion polymerization mechanism possess smaller diameter and size distribution than those formed under similar conditions via the miniemulsion polymerization mechanism. Other differences between these two polymerization mechanisms have also been elucidated. For future study, we wish to use these nanoparticles for the covalent immobilization of bioactive reagents such as proteins to the surface of these nanoparticles for various biomedical applications.     

Preparation of magnetite/poly(styrene-divinylbenzene) nanoparticles for selective enrichment-determination of fenitrothion in environmental and biological samples

In the present study, a cross-linked nano-sized spherical magnetic poly(styrene-divinylbenzene) is synthesized and used as an adsorbent for enrichment-determination of fenitrothion. A miniemulsion polymerization procedure was used to prepare the adsorbent. The magnetic adsorbent was characterized by FT-IR, SEM and TEM. The prepared magnetic adsorbent nanoparticles were mixed with magnetite nanoparticles for faster and more efficient magnetic precipitation. The reduced fenitrothion was coupled with 3-methyl-2-benzothiazolinone hydrazone and then the blue colored complex was extracted. The blue derivative of fenitrothion was eluted by a 1 mL aliquot of 1-propanol prior to spectrophotometry at 571 nm. Beer's law was obeyed in the range of 2–230 ng mL⁻¹ of fenitrothion with relative standard deviation and recovery in the ranges of 0.9–5.1% and 97.2–100.0%, respectively. Selectivity of the method was evaluated, and the method was successfully applied to the determination of fenitrothion in various water, soil, urine and human plasma samples.     

New rod-coil block copolymers consisting of terfluorene segments and electron transporting units as the flexible blocks

A series of new rod-coil block copolymers having a well-defined terfluorene unit as the rigid segment with three different electron transporting moieties as the flexible part, such as side chain oxadiazole (TFPOXD), side chain quinoline (TFPQN) and a molecule containing two oxadiazole rings in the side chain (TFPDOXD), were synthesized using the atom transfer radical polymerization (ATRP) technique. All the synthesized copolymers were extensively examined with respect to their optical properties as pristine films, upon thermal annealing (200 °C for 30 min in air) and photo-oxidation treatment in air. Thermal annealing of the block copolymers resulted in stable blue light emission from TFPOXD and TFPDOXD while TFPQN showed the appearance of the undesired 520 nm emission band. In addition, TFPOXD does not exhibit the low-energy emission band at 520 nm after photo-oxidation under prolonged diffuse UV radiation at ambient atmosphere, despite the fluorenone formation on the terfluorene segment, in contrast to all the other copolymers.     

Synthesis of gold nanoparticle necklaces using linear-dendritic copolymers

Linear-dendritic copolymers containing hyperbranched poly(citric acid) and linear poly(ethylene glycol) blocks (PCA-PEG-PCA) were used as reducing and capping agents to synthesize and support gold nanoparticles (AuNPs). PCA-PEG-PCA copolymers with 1758, 1889 and 3446 molecular weights, called A1, A2 and A3 through this work, respectively, were synthesized using 2, 5, and 10 citric acid/PEG molar ratios. The diameter of A1, A2 and A3 in a fresh water solution was investigated using dynamic light scattering (DLS) and it was between 1.8 and 2.8 nm. AuNPs were simply synthesized and supported by addition a boiling aqueous solution of HAuCl₄ to aqueous solutions of A1, A2 and A3. Supported AuNPs were stable in water for several months and agglomeration was not occurred. The loading capacity of A1, A2 and A3 and the size of synthesized AuNPs were investigated using UV spectroscopy and transmission electron microscopy (TEM). It was found that the loading capacity of PCA-PEG-PCA copolymers depend on the concentration of copolymers and the size of their poly(citric acid) parts directly. For example average loading capacities for 400 μM concentration of A1, A2 and A3 were 32.24, 37.4 and 41.52 μM, respectively, and average loading capacities for 400, 200 and 100 μM concentration of A1 were 32.24, 20.28 and 9.1 μM, respectively. Interestingly there was a reverse relation between the size of synthesized AuNPs and size of poly(citric acid) parts of PCA-PEG-PCA copolymers.     

Methoxy poly(ethylene glycol)-b-poly(valerolactone) diblock polymeric micelles for enhanced encapsulation and protection of camptothecin

Amphiphilic block copolymers, methoxy poly(ethylene glycol)-b-poly(valerolactone) (mPEG-b-PVL), were synthesized via ring opening polymerization of δ-valerolactone in the presence of methoxy poly(ethylene glycol) (mPEG). The copolymers form micelle-like nanoparticles by their amphiphilic characteristics and their structures were examined by Nuclear Magnetic Resonance (NMR). The sizes of nanoparticles ranged from 60 to 120 nm as measured by dynamic light scattering detection, and were larger with higher molecular weight of the copolymers. The Critical Micelle Concentration (CMC) of these nanoparticles in water decreased with increasing molecular weight of hydrophobic segment. Stability analysis showed that the micellar solutions maintain their sizes at 37 °C for six weeks without aggregation or dissociation. The lyophilization method was better than the evaporation method when camptothecin (CPT) was incorporated to the micelles. The former method yielded higher CPT loading efficiency and lower aggregation. The loading efficiency of CPT could be more than 96% and a steady release rate of CPT was kept for twenty six days. Moreover, the mPEG-b-PVL polymeric micelles offered good protection of CPT lactone form at 37 °C for sixteen days. The copolymers showed no cytotoxicity towards L929 mouse muscular cells when incubated for one day. Taken together, the mPEG-b-PVL copolymer has potential to be used for the delivery of CPT or other similar drugs.     

Self-aggregated nanoparticles of cholesterol-modified glycol chitosan conjugate: Preparation, characterization, and preliminary assessment as a new drug delivery carrier

Cholesterol-modified glycol chitosan (CHGC) conjugate was synthesized and characterized by FTIR and ¹H NMR. The degree of substitution (DS) was 6.7 cholesterol groups per 100 sugar residues of glycol chitosan. CHGC formed self-aggregated nanoparticles with a roughly spherical shape and a mean diameter of 228 nm by probe sonication in aqueous medium. The physicochemical properties of the self-aggregated nanoparticles were studied using dynamic light scattering (DLS), transmission electron microscopy (TEM) and fluorescence spectroscopy. The critical aggregation concentration (CAC) of self-aggregated nanoparticles in aqueous solution was 0.1223 mg/mL. Indomethacin (IND), as a model drug, was physically entrapped into the CHGC nanoparticles by dialysis method. The characteristics of IND-loaded CHGC (IND-CHGC) nanoparticles was analyzed using DLS, TEM and high performance liquid chromatography (HPLC). The IND-CHGC nanoparticles were almost spherical in shape and their size increased from 275 to 384 nm with the IND-loading content increasing from 7.14% to 16.2%. The in vitro release behavior of IND from CHGC nanoparticles was studied by a dialysis method in phosphate buffered saline (PBS, pH 7.4). IND was released in a biphasic way. The initial rapid release in 2 h and slower release for up to 12 h were observed. The results indicated that CHGC nanoparticles had a potential as a drug delivery carrier.     

Miniemulsion polymerization of styrene costabilized with polyurethane via <Superscript>60</Superscript>Co γ-ray radiation initiation

Polyurethane (PU) was successfully synthesized and used as costabilizer in the miniemulsion polymerization of styrene (St) initiated by ⁶⁰Co γ-ray radiation at room temperature. Only 2 wt% PU based on the monomer was enough to prepare a stable miniemulsion with a shelf life of more than 12 months. Preservation of original particle size and distribution throughout the polymerization observed from dynamic light scattering measurements indicates the predominance of monomer droplet nucleation. Kinetic analysis shows that there is no constant rate stage, which also suggests a droplet nucleation mechanism. Polystyrene (PS) nanoparticles with relatively small diameters (40–70 nm) and narrow size distribution could be easily prepared. The effects of surfactant, costabilizer, and absorbed dose rate on the miniemulsion polymerization were discussed.     

Synthesis and characterization of thermo-responsive copolymeric nanoparticles of poly(methyl methacrylate-co-N-vinylcaprolactam)

Copolymeric nanoparticles of methyl methacrylate (MMA) and N-vinylcaprolactam (VCL) were prepared through free radical polymerization using hydrogen peroxide and l-ascorbic acid as a redox initiator in o/w microemulsion containing sodium dodecyl sulphate (SDS). The copolymers were characterized by FTIR and gel permeation chromatography (GPC) and composition of copolymer was determined by ¹H NMR spectroscopy. Reactivity ratio was determined by linear least square and non-linear least square methods. The morphology and particle size distribution of copolymer latexes was determined through transmission electron microscopy (TEM) and dynamic light scattering (DLS). Copolymers were of less than 50 nm size with spherical morphology and latexes were stable for more than 6 months. Phase transition temperature measured through UV-vis spectrometry, for the synthesized copolymer indicates their potential use in biosensors and targeted drug delivery system. Cytotoxicity of nanoparticles was determined by MTT assay on B16F10 melanoma cell lines. Cell viability data shows the IC₅₀ values of copolymeric nanoparticles to be in the range of 0.01-0.1 mg/mL.     

Novel fluorescent amphiphilic block copolymers: Controllable morphologies and size by self-assembly

New fluorescent amphiphilic copolymers polyacrylamide-b-poly(p-methacrylamido)acetophenone thiosemicarbazone (PAM-b-PMATC) were synthesized by atom transfer radical polymerization (ATRP) method. The structures of polymers were confirmed by ¹H NMR and gel permeation chromatography-multi-angle laser light scatting (GPC-MALLS). PAM-b-PMATC showed a broad emission peak about 388 nm excited at 318 nm in aqueous solution. The self-assembly behavior of PAM-b-PMATC in the binary mixture formamide/water was observed by transmission electron microscope (TEM). It indicated that PAM-b-PMATC-I and -II with the same PAM block self-assembled to vesicles and sunflower-like micelles. The water fraction in the mixture could control the size and thickness of vesicles. Vesicle size increased from 50 to 420 nm and vesicle thickness changed from 5 to 50 nm with water content ranging from 33 to 90 vol.%. In addition, the cytotoxicity in vitro of PAM-b-PMATC-I and its nanoparticles loaded with methotrexate (MTX) were evaluated by MTT assay.     

Synthesis of liquid‐filled nanocapsules via the miniemulsion technique

This study describes the synthesis of well‐defined nanocapsules via the miniemulsion technique. Pentaerythritol tetrakis(3‐mercaptopropionate) (TetraThiol) or 1,6‐hexanediol di(endo, exo‐norborn‐2‐ene‐5‐carboxylate) (DiNorbornene) is used as the oil phase. TetraThiol is encapsulated via the miniemulsion technique without polymerization, as this monomer would simultaneously act as a chain‐transfer agent, and DiNorbornene is encapsulated via miniemulsion polymerization of styrene. Various styrene‐maleic anhydride (PSMA) copolymers and poly(styrene‐maleic anhydride)‐block‐polystyrene (PSMA‐b‐PS) block copolymers were used as surfactant for the synthesis of well‐defined nanocapsules with TetraThiol as the core material. The nanocapsules had a diameter of 150–350 nm and the particle size distribution was narrow. The use of PSMA‐b‐PS block copolymers as surfactant in combination with post‐addition of formaldehyde provided improved stability to the nanocapsules. DiNorbornene was encapsulated via miniemulsion polymerization of styrene, and a stable latex with a bimodal particle size distribution was obtained. The distribution of small particles had a size of 60 nm and the distribution of large particles had a size of 150 nm. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Synthesis and surface characterization of an amphiphilic fluorinated copolymer via emulsifier-free emulsion polymerization of RAFT

The hydrophobic monomer dodecafluoroheptyl methacrylate has been copolymerized with hydrophilic monomer methacrylic acid in aqueous solution without any additional emulsifier used via a two-step polymerization process of RAFT. The FTIR and GPC results indicated that amphiphilic copolymers with a narrow molecular weight distribution and well-defined blocks have been synthesized successfully. And the copolymers are likely to form steady micelles in the emulsion. Indicated by TEM, it is clear that micelles with a diameter of 70-120 nm have been formed. Despite a content of 22 wt% of hydrophilic carboxyl, films formed by casting the emulsion onto the baseplate can be hydrophobic after heating treatment.     

Preparation, characterization and enzyme inhibition of methylmethacrylate copolymer nanoparticles with different hydrophilic polymeric chains

Methylmethacrylate copolymer nanoparticles with different hydrophilic chains were prepared by the free radical polymerization of methylmethacrylate with N-isopropylacrylamide (NIPAAm), N-methacrylic acid (MAA), N-trimethylaminoethylmethacrylate chloride (TMAEMC) or N-dimethylaminoethylmethacrylate hydrochloride (DMAEMC). These particles were characterized by particle size and zeta potential. The polymerization conditions were shown to influence the particle size and surface charge. Particle sizes of MMA-NIPAAm nanoparticles after 3 h of reaction reached constant level at 180 nm. An increasing amount of total monomer (0.5-5%) would result in the nanoparticles of particle size of 115-204 nm for 30% NIPAAm of the total monomer. In the same range of 5-40% NIPAAm of the total monomer, the particle size decreased from 280 to 170 nm. The concentration of the initiator APS up to a concentration of 0.2% for MMA-TMAEMC and 0.1% for MMA-NIPAAm showed no effect on the particle size of the final nanoparticle suspensions, while higher concentration would lead to aggregation in the polymerization process. MMA-NIPAAm nanoparticles were pH-dependent in zeta potential at pH 1-12 values reducing from 12.2 mV to −16.8 mV, respectively. Nanoparticles were incubated with pepsin and trypsin at 37 °C for 20 min and their enzyme inhibition was determined. The activity of pepsin decreased to 27% in the presence of MMA-NIPAAm nanoparticles, and MMA-MAA nanoparticles reduced the activity of trypsin to 39%, respectively.     

PEO coated magnetic nanoparticles for biomedical application

This paper reports on the preparation, characterization and stealthiness of superparamagnetic nanoparticles (magnetite Fe₃O₄) with a 5 nm diameter and stabilized in water (pH ? 6.5) by a shell of water-soluble poly(ethylene oxide) (PEO) chains. Two types of diblock copolymers, i.e., poly(acrylic acid)-b-poly(ethylene oxide), PAA-PEO, and poly(acrylic acid)-b-poly(acrylate methoxy poly(ethyleneoxide)), PAA-PAMPEO, were prepared as stabilizers with different compositions and molecular weights. At pH ? 6.5, the negatively ionized PAA block interacts strongly with the positively-charged nanoparticles, thus playing the role of an anchoring block. Aggregates of coated nanoparticles were actually observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter was in the 50-100 nm range and the aggregation number (number of nanoparticles per aggregate) was lying between several tens and hundred. Moreover, the stealthiness of these aggregates was assessed “in vitro” by the hemolytic CH50 test. No response of the complement system was observed, such that biomedical applications can be envisioned for these magnetic nanoparticles. Preliminary experiments of magnetic heating (10 kA/m; 108 kHz) were performed and specific absorption rate varied from 2 to 13 W/g_(Fe).     

Controlled,radical reversible addition–fragmentation chain‐transfer polymerization in high‐surfactant‐concentration ionic miniemulsions

Living free‐radical polymerization of methacrylate and styrenic monomers with ionic surfactants was carried out with reversible addition–fragmentation chain transfer in miniemulsion with different surfactant types and concentrations. The previously reported problem of phase separation was found to be insignificant at higher surfactant concentrations, and control of the molar mass and polydispersity index was superior to that of published miniemulsion systems. Cationic and anionic surfactants were used to examine the validity of the argument that ionic surfactants interfere with transfer agents. Ionic surfactants were suitable for miniemulsion polymerization under certain conditions. The colloidal stability of the miniemulsions was consistent with the predictions of a specific model. The living character of the polymer that comprised the latex material was shown by its transformation into block copolymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 960–974, 2004