Cross-Linked Polymer Microparticles Research Articles

Sustainable Light‐Stimulated Synthesis of Cross‐Linked Polymer Microparticles

AbstractThe increasing demand for crosslinked polymer microparticles (PMPs) in advanced applications requires the development of new sustainable methods which can reduce the impact of the polymerization process on the environment. This research reports a new environmentally‐friendly light‐assisted polymerization method for the synthesis of highly cross‐linked polymer microspheres by combining light‐induced [2+2] cycloadditions with dispersion polymerization. Using naturally‐occurring coumarin as reactive moieties, this method allows the synthesis of highly crosslinked PMPs in the presence of UV light at room temperature without initiator. The effect of the reaction parameters such as monomer concentration, stabilizer and reaction time on the particle size and yield are investigated using a number of techniques including Fourier transform infrared spectroscopy, solid‐state13C nuclear magnetic resonance spectroscopy, and scanning electron microscopy. The results show the formation of highly crosslinked porous microspheres which demonstrate good thermal stability.

Cross-linked polymer microparticles with tunable surface properties by the combination of suspension free radical copolymerization and Click chemistry

We propose a general, versatile and broad in scope two-steps approach for the elaboration of cross-linked polymer microparticles (µPs) with tunable functionalities and surface properties. Surface-functionalized cross-linked polymer µPs with diameter in the 80 μm range are prepared by the combination of: 1) suspension free radical copolymerization of styrene, propargyl methacrylate and 1,6-hexanediol dimethacrylate, 2) subsequent covalent tethering of a variety of azide-functionalized moieties (i.e. rhodamine B fluorescent dye or poly(ethylene glycol) (PEG) brush precursor) by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and, 3) optional N-alkylation of the 1,2,3-triazole groups followed by anion exchange reaction to afford covalently-tethered 1,2,3-triazolium ionic liquids with iodide or cresol red counter-anions. The resulting µPs are characterized by laser diffraction, differential scanning calorimetry, as well as by optical, confocal fluorescence, scanning electron and atomic force microscopies. Finally, the rheological properties of concentrated suspensions (volume fractions of 0.40 and 0.44) of the different synthesized µPs dispersed in a 1:1 (vol/vol) mixture of polyalkylene glycol and water are studied. The modification of µPs surface properties contributes not only to change the stability of the suspensions against flocculation, but also to significantly modify their rheological behavior at high shear stresses. This represents a clear experimental evidence of the importance of non-hydrodynamic contact forces in the rheology of non-Brownian suspensions (NBSs).

Molecularly imprinted microspheres prepared by precipitation polymerization at high monomer concentrations

AbstractHighly crosslinked polymer microparticles have been prepared by precipitation polymerization using high monomer loadings (≥25 v/v %) which generally would lead to bulk monoliths. The microparticle format was achieved by the use of non-solvating diluents either alone or in combination with co-solvents. Two distinct morphologies were observed. Monodisperse smooth microspheres were obtained using a thermodynamically good co-solvent whereas segmented irregular particles were formed with poorer co-solvents. It has been found that during polymerization the forming polymer particles were enriched in the co-solvent and this effect was more pronounced when good co-solvents were used. The type of functional monomer, crosslinker and co-solvent, and the non-solvent/co-solvent ratio were identified as influential parameters on the microparticle morphology. With the proposed methodology molecularly imprinted microparticles have been prepared successfully for three different templates, naproxen, diclofenac and toltrazuril using various functional monomers, crosslinkers and polymerization solvent mixtures.

Crosslinked microparticle preparation in supercritical carbon dioxide with photopolymerization

An antisolvent processing technique by simultaneous compressed antisolvent precipitation and photopolymerization for cross-linked polymer microparticles formation was presented in this paper. In this process, photopolymerization of the homogeneous solution composed of methylene chloride, poly(ethylene glycol)600 diacrylate (PEG600DA) as monomer and diphenyl-(2,4,6-trimethylbenzoyl)-phosphine oxide (TPO) or 2,2-dimethoxy-2-phenylacetophenone (DMPA) as photoinitiator resulted to microparticle when it was sprayed into supercritical carbon dioxide (scCO2) and simultaneously exposed to initiating light. High miscibility of the solvent in scCO2 made methylene chloride quickly extracted from the dispersion phase, leaving very high concentrations of monomer (PEG600DA) dispersed in scCO2. The high monomer concentration combined with photo initiating polymerization facilitates rapid reaction rates and ultimately lead to polymer precipitation. Particle size and morphology were adjustable by changing the processing conditions, such as temperature and pressure. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Criteria for the preparation of cross-linked poly(meth)acrylate microparticles by solution free radical polymerization

Cross-linked polymer microparticles (CPMs) with nanoscopic size were synthesized from the free radical polymerization of acrylate/diacrylate mixtures or of their methacrylate counterparts. The syntheses were carried out in solution, and the study of the influence of the solvent on the CPM characteristics led to the definition of reliable criteria for the obtention of true, soluble, individualized microgels and for avoiding macro-gelation, when starting from any desired monomer combination. Two main parameters could be pointed out: first, the probability of propagation of the growing radicals, q, (or the kinetic chain length λ = 1/1 − q) that must be kept below a certain threshold value in order to prevent macrogelation; q may be adjusted by playing on the monomer, initiator and transfer agent concentrations. The second essential criterion is the ability of the copolymer for auto-stabilization in the chosen solvent (that may be adjusted by the use of a suitable stabilizing co-monomer in case the quality of the solvent would not be sufficient), in order to avoid flocculation and interparticular reactions. By controlling these two parameters, the preparation of CPMs becomes possible over a wide range of concentration and composition.

Cross-Linked Cationic Polymer Microparticles: Effect of N-Trimethyl Chitosan Chloride on the Release and Permeation of Ibuprofen

Cross-Linked Cationic Polymer Microparticles: Effect of N-Trimethyl Chitosan Chloride on the Release and Permeation of Ibuprofen

Cross-Linked Cationic Polymer Microparticles: Effect of N-Trimethyl Chitosan Chloride on the Release and Permeation of Ibuprofen

Microparticles made by cross-linking hydrophilic polymers, such as chitosan, have been used to modify the release rate of a loaded drug. In this study a polymer with fixed positive charges, N-trimethyl chitosan chloride (TMC), was used in combination with chitosan to formulate microparticles to investigate its effects on drug release rate and transport across intestinal epithelial cells. The microparticles were prepared by cross-linking these cationic polymer(s) using sodium citrate as the ionic cross-linker. This process was done under homogenization and ultrasonication to control the size of the particles. The addition of TMC to the chitosan microparticles resulted in an increase in particle size of the microparticles and an increase in ibuprofen release rate as compared to the microparticles containing chitosan alone. Permeation of ibuprofen across Caco-2 cell monolayers, after administration of a suspension of the microparticles to the apical side, was not significantly different for the microparticles containing TMC as compared to those consisting of chitosan alone. It was concluded that release of TMC molecules from the microparticles was probably not sufficient to interact with the intestinal epithelial cells in order to change the permeation of the released drug.

Compressed Antisolvent Precipitation and Photopolymerization To Form Highly Cross-Linked Polymer Particles

We present a novel antisolvent processing technique by simultaneous compressed antisolvent precipitation and photopolymerization for forming cross-linked polymer microparticles. In this process, an organic solvent dissolves monomer and polymerization photoinitiators to form a homogeneous solution. Photopolymerization and microparticle formation occur when the homogeneous solution is sprayed into a compressed antisolvent while being simultaneously exposed to initiating light. High miscibility of the solvent in the supercritical antisolvent allows for its quick extraction from the polymerizing phase, leaving progressively higher concentrations of monomer. The high monomer concentration combined with photoinitiated polymerization facilitates rapid reaction rates and ultimately results in polymer precipitation. Particle size and morphology are adjustable by changing the processing conditions, as simultaneous polymerization and solvent extraction result in microparticles with a wide range of diameters.

Rheological Properties of (Meth)acrylic Cross-Linked Polymer Microparticles, 2. Role of Interactions in Non-Reactive and in Reactive Diluents. Copolymerization Studies

The rheological properties of (meth)acrylic cross-linked polymer microparticle solutions have been studied regarding the influence of physical interactions. Cross-linked polymer microparticles (CPM) were synthesized with different functionalities: epoxy, acrylic, carboxyl, hydroxyl, octadecyl and methyl. The viscosities of either dilute or concentrated solutions in non-reactive solvent (xylene) and in reactive solvents (styrene and isobornyl acrylate monomer) have been measured for each type of CPM. A very weak effect of functionality was noticed on the intrinsic viscosity of CPM, whatever the solvent. Only carboxyl groups had a significant influence by increasing the viscosity because of hydrogen bonding. Greater effects were shown on the rheological properties of concentrated solutions. All solutions exhibited shear-thinning behavior when the solvent was xylene or styrene. Carboxyl functionalized CPM still led to higher viscosity, while octadecyl groups reduced the low shear limiting viscosity. The recovery time was strongly increased for CPM with epoxy and acrylic functionalities when styrene was used instead of xylene, whereas it remained the same for all other CPM solutions. In isobornyl acrylate monomer, only CPM functionalized epoxy and acrylic showed shear-thinning behavior, the other solutions being Newtonian. Finally a copolymerization study has been done on three solutions, containing either non-reactive CPM in reactive diluent, or reactive CPM in non-reactive diluent, or reactive CPM in reactive diluent. This study confirmed the cross-linking mechanism of acrylic systems. First, intramolecular reaction took place within the CPM and small aggregates were formed. Then these aggregates interconnected leading to a viscoelastic solid.

(Meth)acrylic Cross-Linked Polymer Microparticles: Synthesis by Dispersion Polymerization and Particle Characterization

(Meth)acrylic cross-linked polymer microparticles have been synthesized by dispersion polymerization in organic media. They were produced by radical copolymerization of mono(meth)acrylate monomers with a certain concentration of a diacrylate as cross-linker, in a mixture of two organic solvents, heptane and propan-2-ol. The reactive surfactant (“surfmer”) was a low solubility parameter acrylate monomer, based on an aliphatic ester group (generally C18) or an isobornyl cycle, which gave auto-dispersing character to the microparticles. By using glycidyl methacrylate in the monomer mixture, oxirane groups were introduced in the particles. The influence of the major synthesis parameters such as solvent composition, monomer composition and concentration, and initiator concentration has been investigated regarding the size and the molar mass of the cross-linked polymer microparticles. The study was completed with the influence of the nature and the concentration of the surfmer, the concentration of cross-linking agent and the composition of monomers feed. Stable cross-linked microparticles ranging from z-average radius of gyration, Rz = 20 nm to Rz > 60 nm were obtained by varying the synthesis conditions. The smallest microparticles were prepared with a blend of heptane and propan-2-ol in the 50/50 ratio by weight. Increasing the surfmer concentration or reducing the monomer concentration in the reaction mixture usually led to smaller microparticles. The longer the aliphatic chain of the surfmer, the smaller the microparticles. Minimum sizes were obtained for cross-linking agent concentrations between 5 and 7.5 mol-%, depending on monomers composition. For higher concentrations, macrogelation may occur during the synthesis.

Rheological Properties of (Meth)acrylic Cross-Linked Polymer Microparticles, 1. Comparison with Linear Polymers in Bulk and in Non-Reactive Solvents

The rheological properties of cross-linked polymer microparticle (CPM) solutions have been studied regarding the influence of the CPM structure. CPM have been synthesized by dispersion polymerization, with the degree of cross-linking varying between 0 and 10% (i.e., with the concentration of diacrylate monomer cross-linking agent ranging from 0 to 10 mol-%). The structure of the CPM has also been changed by using optionally a semi-crystalline stabilizing agent monomer, based on a C18 aliphatic chain. The resulting CPM were either semi-crystalline or totally amorphous with a high Tg. Typical linear acrylic polymers (acrylic LP) have also been synthesized by solution polymerization and compared to the CPM. Dilute solutions in toluene or xylene were used to measure the intrinsic viscosity of polymers with a capillary viscosimeter. More concentrated solutions in the same solvents were used to determine the influence of the shear rate and of the CPM structure and concentration on the solution viscosity with a cone and plate viscosimeter. Because of the intramolecular cross-links, weak interactions took place in dilute solutions between the CPM, resulting in very low viscosity and low dependence on the molar mass, with respect to the acrylic LP. A low molar mass dependence was also found for CPM in bulk, without critical molar mass due to chain entanglement. Concentrated CPM solutions led to shear thinning behavior. It greatly depended on the microparticle structure, especially on the presence of the C18 aliphatic chains. Solutions of cross-linked polymer microparticles without these aliphatic chains can decrease the viscosity by 500 times between low and high shear rates. Thixotropy was observed for CPM solutions with concentrations higher than 20 wt.-%. The recovery time was highly influenced by the CPM concentration, ranging from a few tens of seconds to about two minutes.

Rheological Properties of (Meth)acrylic Cross-Linked Polymer Microparticles, 1. Comparison with Linear Polymers in Bulk and in Non-Reactive Solvents

The rheological properties of cross-linked polymer microparticle (CPM) solutions have been studied regarding the influence of the CPM structure CPM have been synthesized by dispersion polymerization, with the degree of cross-linking varying between 0 and 10% (i.e., with the concentration of diacrylate monomer cross-linking agent ranging from 0 to 10 mol-%). The structure of the CPM has also been changed by using optionally a semi-crystalline stabilizing agent monomer, based on a C 18 aliphatic chain. The resulting CPM were either semi-crystalline or totally amorphous with a high T g . Typical linear acrylic polymers (acrylic LP) have also been synthesized by solution polymerization and compared to the CPM. Dilute solutions in toluene or xylene were used to measure the intrinsic viscosity of polymers with a capillary viscosimeter. More concentrated solutions in the same solvents were used to determine the influence of the shear rate and of the CPM structure and concentration on the solution viscosity with a cone and plate viscosimeter. Because of the intramolecular cross-links, weak interactions took place in dilute solutions between the CPM, resulting in very low viscosity and low dependence on the molar mass, with respect to the acrylic LP. A low molar mass dependence was also found for CPM in bulk, without critical molar mass due to chan entanglement. Comcentrated CPM solutions led to shear thinning behavior. It greatly depended on the microparticle structure, especially on the presence of the C 18 aliphatic chains. Solutions of cross-linked polymer microparticles without these aliphatic chains can decrease the viscosity by 500 times between low and high shear rates. Thixotropy was observed for CPM solutions with concentrations higher than 20 wt.-%? The recovery time was highly influenced by the CPM concentration, ranging from a few tens of seconds to about two minutes.

Rheological Properties of (Meth)acrylic Cross-Linked Polymer Microparticles, 2. Role of Interactions in Non-Reactive and in Reactive Diluents. Copolymerization Studies

Rheological Properties of (Meth)acrylic Cross-Linked Polymer Microparticles, 2. Role of Interactions in Non-Reactive and in Reactive Diluents. Copolymerization Studies

(Meth)acrylic Cross-Linked Polymer Microparticles: Synthesis by Dispersion Polymerization and Particle Characterization

(Meth)acrylic Cross-Linked Polymer Microparticles: Synthesis by Dispersion Polymerization and Particle Characterization