Free Radical Dispersion Polymerization Research Articles

Synthesis and Characterization of N-Isopropylacrylamide Microspheres as pH Sensors.

Swellable polymer microspheres that respond to pH were prepared by free radical dispersion polymerization using N-isopropylacrylamide (NIPA), N,N′-methylenebisacrylamide (MBA), 2,2-dimethoxy-2-phenylacetylphenone, N-tert-butylacrylamide (NTBA), and a pH-sensitive functional comonomer (acrylic acid, methacrylic acid, ethacrylic acid, or propacrylic acid). The diameter of the microspheres was between 0.5 and 1.0 μm. These microspheres were cast into hydrogel membranes prepared by mixing the pH-sensitive swellable polymer particles with aqueous polyvinyl alcohol (PVA) solutions followed by crosslinking with glutaric dialdehyde for use as pH sensors. Large changes in the turbidity of the PVA membrane were observed as the pH of the buffer solution in contact with the membrane was varied. These changes were monitored by UV–visible absorbance spectroscopy. Polymer swelling of many NIPA copolymers was reversible and independent of the ionic strength of the buffer solution in contact with the membrane. Both the degree of swelling and the apparent pKa of the polymer microspheres increased with temperature. Furthermore, the apparent pKa of the polymer particles could be tuned to respond sharply to pH in a broad range (pH 4.0–7.0) by varying the amount of crosslinker (MBA) and transition temperature modifier (NTBA), and the amount, pKa, and hydrophobicity of the pH-sensitive functional comonomer (alkyl acrylic acid) used in the formulation. Potential applications of these polymer particles include fiber optic pH sensing where the pH-sensitive material can be immobilized on the distol end of an optical fiber.

Comparison of polymeric particles synthesised using scCO2 as the reaction medium on the millilitre and litre scale

We describe the first steps to scale-up the free radical dispersion polymerization of poly(methyl methacrylate) (PMMA) from the millilitre to the litre scale, utilising supercritical carbon dioxide (scCO2) as the reaction medium. Our key focus is to develop a reproducible and controlled reactor system that produces well-defined polymer particles with narrow size distribution. Two different approaches to monomer addition were investigated, along with variations of surfactant concentration to consistently achieve control of particle size on the large and small scale. Comparison of scanning electron microscopy images from the 60 mL and 1 L vessel demonstrated that very similar particle sizes and morphologies were obtained at high yield (> 90 %) on the small and the large scale. The impact of the differences between the two vessels and their influence on this well understood reaction was investigated.

Synthesis of Near-monodisperse Polyacid Particles Containing Phosphate Groups by Free Radical Dispersion Polymerization

Near-monodisperse, submicrometer-sized, colloidally stable polyacid particles containing phosphate groups were synthesized by free radical dispersion polymerization of acid phosphoxy polyoxyethylen...

Aqueous Dispersions of Ethylene Copolymers and Their Laponite Clay Nanocomposites from Free-Radical Dispersion Polymerization

Aqueous dispersions of ethylene copolymers with polar comonomers are of practical interest, e.g., as additives for paints or water-based adhesives. We report insights on the free-radical heterophas...

Colloidal Stabilizer-Assisted Polymerization-Induced Precipitation Method for Colloidally Stable Polyacid Particles.

Near-monodispersed, colloidally stable, submicrometer-sized poly(acid phosphoxy ethyl methacrylate) (PAPEMA) latex particles were synthesized by free-radical dispersion polymerization using poly( N-vinylpyrrolidone) (PNVP) as both a steric colloidal stabilizer and a precipitating agent. Polymerization in the absence of PNVP led to a homogeneous transparent solution of PAPEMA, which indicates that the PNVP is essential for latex formation and the complex of PNVP and PAPEMA was formed during the dispersion polymerization. Dispersion copolymerizations with a divinyl cross-linking comonomer (∼20 wt % based on acid phosphoxy ethyl methacrylate) were also successful in synthesizing near-monodispersed, colloidally stable cross-linked PAPEMA latex particles, and the softness and p Ka values of the resulting PAPEMA latex particles can be controlled by varying the divinyl comonomer concentration. These sterically stabilized latex particles were characterized by electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, elemental microanalysis, and Fourier transform infrared spectroscopy. Characterization results indicated that the PNVP colloidal stabilizer was likely to be located homogeneously on the particle surfaces and within the interior of particles. Finally, it was demonstrated that the PAPEMA latex particles worked as an effective surface modifier for metal surfaces.

Antimicrobial peptide encapsulation and sustained release from polymer network particles prepared in supercritical carbon dioxide

Antimicrobial peptide loaded poly(2-hydroxyethyl methacrylate) particles were synthesized in supercritical carbon dioxide via one-pot free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate and a cross-linker. Discrete particles with a well-defined spherical morphology and a diameter as low as 450 nm have been obtained in mild conditions. The encapsulation and release of the peptide were confirmed by antimicrobial tests that demonstrated for the first time a sustained release of the peptide from poly(2-hydroxyethyl methacrylate) microgels prepared by one-pot dispersion polymerization in supercritical carbon dioxide and then dispersed in water.

Sulindac encapsulation and release from functional poly(HEMA) microparticles prepared in supercritical carbon dioxide

Sulindac loaded poly(HEMA) cross-linked microparticles were synthesized via one-pot free-radical dispersion polymerisation in supercritical carbon dioxide (scCO2) in presence of photocleavable diblock stabilisers based on polyethylene oxide (PEO) and poly(heptadecafluorodecyl acrylate) (PFDA) bearing a o-nitrobenzyl photosensitive junction (hv) (PEO-hv-PFDA), and ethylene glycol dimethacrylate (EGDMA) as cross-linker. Poly(HEMA) cross-linked microparticles either empty or sulindac loaded were obtained with well-defined spherical morphology with the sizes between 250 and 350 nm. Additionally, upon UV-photolysis the stabiliser on the surface was cleaved which permits to microparticles to be redispersed in water leading to water swollen microgels about 2.1–3.6 µm. Moreover, the release behaviour from obtained microgels indicated the sustained release of sulindac over 10 days. Besides, the surface modification after UV-photolysis was studied and proved that the particles can be functionalised with further chemistries.

PH-Responsive Aqueous Bubbles Stabilized With Polymer Particles Carrying Poly(4-vinylpyridine) Colloidal Stabilizer.

Free radical dispersion polymerization was conducted to synthesize near-monodispersed, micrometer-sized polystyrene (PS) particles carrying pH-responsive poly(4-vinylpyridine) (P4VP) colloidal stabilizer (P4VP-PS particles). The P4VP-PS particles were extensively characterized in terms of morphology, size, size distribution, chemical composition, surface chemistry, and pH-response using optical and scanning electron microscopies, elemental microanalysis, X-ray photoelectron spectroscopy, laser diffraction particle size analysis, and zeta potential measurement. The P4VP-PS particles can work as a pH-responsive stabilizer of aqueous bubbles by adsorption at the air-water interface. At and above pH 4.0, where the particles have partially protonated/non-protonated P4VP stabilizer with relatively hydrophobic character, particle-stabilized bubbles were formed. Optical and scanning electron microscopy studies confirmed that the P4VP-PS particles were adsorbed at the air-water interface of the bubbles in aqueous media. At and below pH 3.0, where the particles have cationic P4VP stabilizer with water-soluble character, no bubble was formed. Rapid disruption of the bubbles can be induced by decreasing the pH; the addition of acid caused the in situ protonation of pyridine groups in P4VP, which impart water-soluble character to the P4VP stabilizer, and the P4VP-PS particles were desorbed from the air-water interface. The bubble stabilization/destabilization cycles could be repeated at least five times.

Free-Radical Dispersion Polymerization of Ethylene with Laponite to Polyethylene–Clay Nanocomposite Particles

Composite clay/polymer nanoparticle dispersions have been studied for many different polymers but remained elusive for polyolefins even though polyolefins are an important class of polymers and are also industrially applied in the form of aqueous dispersions. Despite the hydrophobic and apolar nature of polyethylene, aqueous nanocomposite dispersions are formed via heterogeneous free-radical polymerization in the presence of the synthetic smectite clay Laponite-RD at relatively mild conditions (250 atm, 85 °C). The clay nanoplatelets effectively contribute to colloidal stability of the polyolefin particles formed and strongly enhance particle formation during the aqueous polymerization. Evolution of the polymer–clay interaction at an early stage of particle formation is instrumental, and initiator-derived polar end groups are decisively involved. The clay enhances polymerization yields and promotes the formation of smaller particles. Stable dispersions with polymer contents of up to 24% were obtained without the need of additional organic surfactants.

PH-Sensitive Polymeric Nanoparticles Fabricated by Dispersion Polymerization for the Delivery of Bioactive Agents.

Development of pH-responsive nanoparticles capable of rapid degradation in the acidic environments in the endosomes and lysosomes of tumor tissues but relatively more stable in the physiological pH (pH 7.4) is desirable. To show that the number of methoxy groups on the benzene ring of benzaldehyde bisacrylate acetal crosslinkers should affect the rate of hydrolysis of the crosslinkers and in vitro availability of the drug loaded into the nanoparticles. Three pH-sensitive acetal crosslinkers were synthesized and characterized by 1H NMR, 13C NMR, FT-IR and high resolution mass spectroscopy (HR-MS). The nanoparticles were fabricated by free-radical dispersion polymerization method. Hydrolysis studies were carried out on the crosslinkers and nanoparticles; drug release studies were done on docetaxel-loaded nanoparticles at pH 5.0 and pH 7.4. The statisitical experimental design was randomized complete block design followed by analyses of variance with F-test of significance. Pairwise comparison test was used to locate specific differences among parameters of the crosslinkers and the nanopaticles. Scanning electron micrographs showed the formation of spherical particles. Particle size analysis showed that the nanoparticles are within nanosize range with negative zeta potential. Data showed that the rate of hydrolysis and drug release were faster at pH 5.0 compared to pH 7.4. Hydrolysis and drug release studies were dependent on the structure of the acetals: Di(2-methacryloyloxyethoxy)- [2,4,6-trimethoxyphenyl] methane crosslinker showed the fastest rate of hydrolysis, followed by di(2- methacryloyloxyethoxy)-[2,4-dimethoxyphe-nyl] methane and di(2-methacryloyloxyethoxy)-[4-methoxyphenyl] methane. The pH-responsive nanoparticles are suitable for the delivery of bioactive agents, especially anticancer drugs.

NIR upconversion fluorescence glucose sensing and glucose-responsive insulin release of carbon dot-immobilized hybrid microgels at physiological pH.

This work reports the preparation of multifunctional hybrid microgels based on the one-pot free radical dispersion polymerization of hydrogen-bonding complexes in water, formed from hydroxyl/carboxyl bearing carbon dots with 4-vinylphenylboronic acid and acrylamide comonomers, which can realize the simultaneous optical detection of glucose using near infrared light and glucose-responsive insulin delivery.

Mild synthesis of poly(HEMA)-networks as well-defined nanoparticles in supercritical carbon dioxide.

Free-radical dispersion polymerisation of 2-hydroxyethyl methacrylate was carried out in supercritical carbon dioxide (scCO2) in the presence of stabilisers based on polyethylene oxide (PEO) and poly(heptadecafluorodecyl acrylate) (PFDA). Different architectures of copolymers (random, palm-tree and diblock) were tested for their surface tension, cloud point and as a stabilising agent. The diblock architecture was found to be the best candidate resulting in poly(HEMA) spherical particles with a size of 316 nm. Furthermore, the effect of the CO2-phobic block (PEO) in the diblock architecture was investigated by using three different chain lengths (1000, 2000, 5000 g mol-1). By optimizing the stabiliser composition and structure, mild reaction conditions have been identified allowing us to obtain well-defined spherical cross-linked poly(HEMA) particles with a mean diameter of unprecedented low size (216 nm) at a temperature as low as 35 °C.

Amphiphilic Graft Copolymer Nanospheres: From Colloidal Self-Assembly to CO2 Capture Membranes.

Colloidal nanosphere self-assembly effectively generates ordered nanostructures, prompting tremendous interest in many applications such as photonic crystals and templates for inverse opal fabrication. Here we report the self-assembly of low-cost, graft copolymer nanospheres for CO2 capture membranes. Specifically, poly(dimethylsiloxane)-graft-poly(4-vinylpyridine) (PDMS-g-P4VP) is synthesized via one-pot, free radical dispersion polymerization to give discrete monodisperse nanospheres. These nanospheres comprise a surface-anchored highly permeable PDMS layer and internal CO2-philic P4VP spherical core. Their diameter is controllable below the submicrometer range by varying grafting ratios. The colloidal dispersion forms a long-range, close-packed hexagonal array on a substrate by inclined deposition and convective assembly. The array shows dispersion medium-dependent packing characteristics. A thermodynamic correlation is determined using different solvents to obtain stable PDMS-g-P4VP dispersions and interpreted in terms of Flory-Huggins interaction parameter. As a proof-of-concept, the implementation of these nanospheres into membranes simultaneously enhances the CO2 permeability and CO2/N2 selectivity of PDMS-based transport matrixes. Upon physical aging of the solution, the CO2/N2 selectivity is improved up to 26, one of the highest values for highly permeable PDMS-based polymeric membranes.

Abstract B90: Poly (lactide)-based nanoparticles by free-radical dispersion polymerization: Fabrication, characterization and in vitro studies

Abstract We have used the macromonomer method to prepare crosslinked, paclitaxel-loaded PLA-PEG (stealth) nanoparticles using free-radical dispersion polymerization. The nanoparticles were optimized using statistical D-optimal mixture design. Nanoparticle fabrication with poly(lactide) is mainly carried out by the dispersion of preformed polymers which makes it difficult to attach targeting moieties to the surface of the nanoparticle and to produce crosslinked networks; hence we designed a new approach based on dispersion polymerization. Confirmation of nanoparticle synthesis was by scanning electron microscopy. Particle size and size distribution and the zeta potential of the optimized formulation were determined using Zetasizer nano Zs. The release profile of paclitaxel-loaded nanoparticles was determined by high performance liquid chromatography and encapsulated drug was released over 7 days. In vitro cytotoxicity studies were carried out using the CellTiter®glo luminescent cell viability assay in MCF7, MDA-MB-231 (breast cancer) and SK-OV-3 (ovarian cancer) cell lines. The cytotoxicity assay shows that the blank nanoparticle is biocompatible with no toxicity for the duration of the assay compared to medium-only treated controls. Further, the paclitaxel-loaded nanoparticle formulation exhibits similar cytotoxicity compared to free drug in solution against the cancer cell lines tested. In vitro intracellular localization of nanoparticle by confocal microscopy also demonstrated that the nanoparticles are rapidly internalized by MCF-7 cancer cells within one hour probably by nonspecific endocytosis. The stealth nanoparticles are suitable for the design of controlled delivery systems for bioactive agents. Citation Format: Simeon K. Adesina, Emmanuel O. Akala. Poly (lactide)-based nanoparticles by free-radical dispersion polymerization: Fabrication, characterization and in vitro studies. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B90.

Polylactide-Based Paclitaxel-Loaded Nanoparticles Fabricated by Dispersion Polymerization: Characterization, Evaluation in Cancer Cell Lines, and Preliminary Biodistribution Studies

The macromonomer method was used to prepare cross-linked, paclitaxel-loaded polylactide (PLA)-polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton nuclear magnetic resonance and Fourier transform infrared spectra confirm the synthesis of PLA macromonomer and cross-linking agent. The formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared with medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared with paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within 1 h. Preliminary biodistribution studies also show nanoparticle accumulation in tumor xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents.

Polymerization of vinyl pivalate in supercritical carbon dioxide and the saponification for the preparation of syndiotacticity-rich poly(vinyl alcohol)

This paper reports a successful free-radical dispersion polymerization of vinyl pivalate in supercritical carbon dioxide using poly(1H,1H-dihydroperfluorooctyl acrylate) and dimethylsiloxane-g-pyrrolidone carboxylic acid (Monasil PCA) as stabilizers. In both cases, no spherical polymer particles were obtained, which might be due to the high solubility of poly(vinyl pivalate) (PVPi) in supercritical carbon dioxide. The effects of the reaction time, pressure, temperature, monomer loading, stabilizer concentration and initiator concentration on the polymer yield and molecular weight of PVPi were also investigated. In addition, the formation of poly(vinyl alcohol) via saponification of the resulting PVPi is described.

Mesoporous silicon@carbon composites via nanoparticle-seeded dispersion polymerization and their application as lithium-ion battery anode materials

Significant efforts have been devoted to synthesis and characterization of engineered silicon nanostructures able to withstand the large stresses and strains produced by lithium alloying/dealloying reactions during electrochemical cycling. Less attention has been given to ensuring robust connection between silicon and its host structure in the anode. The current work develops a new methodology to create nanocomposites in which silicon nanoparticles are uniformly dispersed in a mesoporous carbon host. The composite is synthesized through copolymerization of acrylonitrile and silicon nanoparticles densely functionalized with vinyl groups, which serve as seeds for free radical dispersion polymerization, followed by carbonization of the PAN coating/network. The method yields nanocomposites with high, reversible capacities and stable cycling performance.

Preparation of poly(vinyl pivalate) microspheres by dispersion polymerization in an ionic liquid and saponification for the preparation of poly(vinyl alcohol) with high syndiotacticity

We report here a successful free-radical dispersion polymerization of vinyl pivalate (VPi) in an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][TFSI]) using poly(vinyl pyrrolidone) (PVP) as a stabilizer. Morphological analysis by FE-SEM revealed that poly(vinyl pivalate) (PVPi) obtained from dispersion polymerizations were in the form of spherical particles. Micron-sized, PVPi particles with a number-average molecular weight ( M n) of 166,400 g/mol could be obtained using 5% stabilizer (w/w to monomer) at 65 °C for 20 h. The effects of varying concentration of stabilizer, initiator and monomer upon polymer yield, molecular weight, and morphology of PVPi were also investigated. Analogous polymerizations in dimethyl sulfoxide (DMSO) and bulk served as references. In addition, the preparation of poly(vinyl alcohol) (PVA) by saponification of the resultant PVPi was described.

Characterization and cell material interactions of PEGylated PNIPAAM nanoparticles

The aim of this study was to investigate the haemocompatibility of poly(N-isopropylacrylamide)-co-poly(ethylene glycol), PNIPAAM-PEG based nanoparticles and the influence of poly(ethylene glycol), PEG on the interactions of nanoparticles with cells. To achieve this purpose, thermosensitive PNIPAAM-PEG nanoparticles were synthesized by free radical dispersion polymerization method. Optimized nanosystems had particle sizes less than 200 nm, low polydispersity and LCST of 40–41 °C. The nanoparticles also showed nearly 83% encapsulation efficiency for doxorubicin HCl with temperature dependent release. Presence of PEG resulted in reduced protein adsorption by more than 50% in comparison to non-PEG containing nanoparticles. Protein adsorption was noted to be dependent on PEG chain length and was the least with M n = 4000. The particles up to a concentration of 2 mg/ml did not show any toxicity on J774 and L929 cell lines. No interactions were observed when NIPAAM-PEG nanoparticles were incubated with blood cells viz. RBCs, neutrophils, platelets and the coagulation system suggesting their haemocompatibility.

Dispersion Polymerization of Methyl Acrylate in Nonpolar Solvent Stabilized by Block Copolymers Formed In situ via the RAFT Process

The free-radical dispersion polymerization of methyl acrylate (MA) in isododecane was carried out in the presence of a poly(2-ethylhexyl acrylate) macromolecular RAFT (reversible addition-fragmentation chain transfer) agent bearing a trithiocarbonate reactive group in the middle of the chain (P2EHA-TTC). The presence of the trithiocarbonate function was crucial for the synthesis of monodisperse colloidal poly(methyl acrylate) (PMA) particles stabilized by the P2EHA segments. The hydrodynamic diameters ranged from 100 to 300 nm, using particularly low amounts of the macro(RAFT agent) (1-6 wt % vs. MA) in dispersion polymerizations carried out at 20 wt % solids content. As shown by 2D liquid chromatography, P2EHA-b-PMA or P2EHA-b-PMA-b-P2EHA block copolymers formed in situ at the early stage of the dispersion polymerization due to the reversible transfer process and played the role of particle stabilizer. The glass-transition temperature of the derived polymer films was not affected by the low amount of the chosen macromolecular stabilizer and the mechanical properties were mainly those of PMA, which makes the technique very attractive for coating applications.