Uniform Polymer Microspheres Research Articles

Uniform Polymer Microspheres by Photoinduced Metal-Free Atom Transfer Radical Precipitation Polymerization.

Herein, a photoinduced method is introduced for the synthesis of highly cross-linked and uniform polymer microspheres by atom transfer radical polymerization (ATRP) at room temperature and in the absence of stabilizers or surfactants. Uniform particles are obtained at monomer concentrations as high as 10% (by volume), with polymers being exempt from contamination by residual transition metal catalysts, thereby overcoming the two major longstanding problems associated with thermally initiated ATRP-mediated precipitation polymerization. Moreover, the obtained particles have also immobilized ATRP initiators on their surface, which directly enables the controlled growth of densely grafted polymer layers with adjustable thickness and a well-defined chemical composition. The method is then employed successfully for the synthesis of molecularly imprinted polymer microspheres.

Synthesis of uniform polymer microspheres with “living” character using ppm levels of copper catalyst: ARGET atom transfer radical precipitation polymerisation

The first example of activators regenerated by electron transfer atom transfer radical polymerisation (ARGET ATRP) under precipitation polymerisation (PP) conditions is reported. This new method for polymer synthesis (called ARGET ATRPP) requires only very low levels of metal catalyst for success, a distinctive feature that enables the production of uniform polymer microspheres under reversible-deactivation radical polymerisation control. The influence of the polymerisation conditions (monomer concentration, reaction time, initiator and catalyst concentrations) on the polymerisations and microsphere products were investigated and optimised. The ARGET ATRPP methodology was used to prepare polymer microspheres with narrow particle size distributions and mean particle diameters in the micron-size range, under dilute monomer conditions (2%) whilst using very low copper catalyst concentrations (down to 1.7 ppm). The “living” characteristics of the polymer microspheres enabled poly(methyl methacrylate) brushes to be grafted-from the microspheres directly without the need for any additional surface functionalisation step to immobilise initiator moieties.

Advances in Uniform Polymer Microspheres and Microcapsules: Preparation and Biomedical Applications

Microspheres and microcapsules have been widely used in biomedical field, such as delivery systems for drugs, vaccines. Uniform particle is required for precise drug delivery and disease treatment, since the particle diameter is a key factor which controls the pharmacokinetics and efficacy of loaded drug. However, there is no universal method to prepare uniform particles either from monomer or preformed polymer raw materials. We have developed two membrane emulsification techniques (MET) to prepare uniform particles with controllable size. In this review, we introduce two MET processes and their mechanisms, and how to develop MET to different emulsion systems to obtain various uniform microspheres and microcapsules with interesting morphologies. Then, the advantages of uniform particles on biomedical application results are focused. Finally, particle design and applications as “Chassis” to form synthetic vaccine are described. What is the most favorite and original chemistry developed in your research group?We clarified the mechanism for obtaining uniform microspheres and microcapsules in O/W, W/O and double emulsion systems, which enabled us to develop the technique to a universal technique, successfully preparing various uniform particles including hydrophobic, hydrophilic and composite functional particles, and leading to the original systematic studies on biomedical applications including “Synthetic Vaccine”.How do you get into this specific field? Could you please share some experiences with our readers?I started the research on preparation of nanospheres from my master course. At that time, I knew there were few universal methods to obtain uniform microspheres and microcapsules. So, after I became an assistant professor, I began to consider this scientific topic.How do you supervise your students?Our group motto is “Enjoy Science, Enjoy Work, Enjoy Life”. I tried to lead the students to like their research, and tried to find interesting results with students together based on their primary experimental results.What is the most important personality for scientific research?Pure, Passion, Perseverance.How do you keep balance between research and family?Work hard, and let my family know I am enjoyable and happy with my research, getting support and encouragement from family.Who influences you mostly in your life?My father. He always read books at the desk. He always gave me encouragement no matter happy or sad.

Catalysis of isocyanate reaction with water by DMF and its use for fast preparation of uniform polyurea microspheres through precipitation polymerization

Highly uniform polymer microspheres are widely used for a variety of applications. Uniform polyurea (PU) microspheres have been prepared by precipitation polymerization of isophorone diisocyanate (IPDI) in a binary mixture of H2O-acetone (AT). With AT replaced by N,N′-dimethylformamide (DMF) in the binary mixture, a significant acceleration effect is observed. Through measurements of the solubility of IPDI and its polymer in the binary solvents of different composition, catalytic effect of DMF is confirmed, and a mechanism of catalysis is proposed. The polymerization is carried out at different temperature with varied IPDI concentration in H2O/DMF or H2O/AT/DMF of different composition, with objective to optimize the preparation of PU microspheres. The results demonstrate that, with the polymerization done at 60 °C in a ternary mixture of H2O-DMF-AT, highly uniform PU microspheres are well formed with IPDI concentration of up to 13.0 wt%, which represents an increase of 3 wt% compared to the highest IPDI concentration allowed to have these microspheres in the binary solvent of H2O-AT. This is also accomplished in an obviously shortened time. PU structure and properties are briefly discussed. This work provides a simple and fast protocol for large-scale production of uniform and functional PU microspheres with DMF as a cosolvent and catalyst.

Preparation of double-emulsion-templated microspheres with controllable porous structures by premix membrane emulsification

A scalable and versatile strategy was developed for the fabrication of uniform polymeric microspheres with controllable interconnected porous structures. Uniform water-in-oil-in-water emulsions with linear poly(methyl methacrylate–glycidyl methacrylate) in the oil phase were generated by two-step premix membrane emulsification and used for constructing the microspheres. During the emulsion solidification process, internal water droplets were packed densely together, forming a thin oil film between the internal and external water phases. After solvent diffusion, the thin film can be ruptured and pores can be templated from the internal water droplets to form interconnected porous structures. Membranes with various pore sizes were obtained. The osmotic pressure and Laplace pressure balance were used to control the porosity and pore size precisely. The proposed method enables the fabrication of functional polymeric microspheres with uniform and controllable porous structures and particle sizes. This improves their performance and broadens the scope of their applications, especially in chromatographic separation.

Dispersion polymerization of uniform cross‐linked polystyrene microspheres in butan‐1‐ol

ABSTRACTButan‐1‐ol can be used as the solvent in the synthesis of poly(styrene‐co‐divinylbenzene‐co‐acrylic acid) microspheres by dispersion polymerization of a mixture of styrene, divinylbenzene (DVB), and acrylic acid (AA). Varying the proportion of the crosslinker DVB affects the size distribution and particle morphology profoundly, with 0.5–1.0% w/w producing spherical particles, whereas 2.0% w/w DVB produces irregular, concave morphologies. Varying the amount of AA from 5–7% w/w increases the average diameter of the spherical particles, whereas 9% w/w AA results in ovoid particles with dimpled surface morphology. In an optimized synthesis using 1.0% w/w DVB and 5% AA, uniform polymer microspheres with an average diameter of 0.8 µm and a coefficient of variation (CV) of diameter of 8.2% are produced. The use of a medium‐polarity solvent, such as butan‐1‐ol, as the solvent for dispersion polymerization will facilitate the incorporation of non‐polar moieties, such as organically‐passivated quantum dots, into the polymer during synthesis. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43103.

Microfluidic Synthesis of Biodegradable Polyethylene-Glycol Microspheres for Controlled Delivery of Proteins and DNA Nanoparticles.

Polymeric microspheres represent an injectable platform for controlling the release of a variety of biologics; microspheres may be combined in a modular fashion to achieve temporal release of two or more biomolecules. Microfluidics offers a versatile platform for synthesizing uniform polymeric microspheres harboring a variety of biologics under relatively mild conditions. Poly(ethylene glycol) (PEG) is a bioinert polymer that can be easily tailored to encapsulate and control the release of biologics. In this study, we report the microfluidic synthesis of biodegradable PEG-based microparticles for controlled release of growth factors or DNA nanoparticles. Simple changes in microfluidic design increased the rate of microparticle formation and controlled the size of the microspheres. Mesh size and degradation rate were controlled by varying the PEG polymer weight percent from 7.5 to 15% (w/v), thus tuning the release of growth factors and DNA nanoparticles, which retained their bioactivity in assays of cell proliferation and DNA transfection, respectively. This platform may provide a useful tool for synthesizing microspheres for use as injectable carriers to achieve coordinated growth-factor or DNA nanoparticle release in therapeutic applications.

Uniform Polymer Microspheres: Monodispersity Criteria, Methods of Formation and Applications

For many applications, polymer microspheres (MS) should possess a monodisperse size distribution. With such uniformity they are able to deliver precise amounts of drug per MS, optimize the release kinetics of an encapsulated drug, obtain repeatable in vivo biodistributions to different organs and tissues, and obtain the maximum protection of (protein) drugs from degradation. This review classifies monodisperse polymer MS according to their methods of production and gives examples of the formation of uniform MS and their applications in the medical field. In the literature, the term 'monodisperse' is often used inaccurately, and this article attempts to rectify this by clearly defining monodispersity in terms of the coefficient of variation and the polydispersity index, the two statistical quantities most frequently used to describe the size distribution of MS.

A facile route to preparation of uniform polymer microspheres by quiescent polymerization with reactor standing still without any stirring

This paper presents a novel and facile route to preparation of highly uniform polymeric microspheres through a quiescent polymerization with the reactor standing still without any stirring. Using one single monomer, isophorone diisocyanate (IPDI), highly uniform polyurea microspheres are achieved with high yield via precipitation polymerization of IPDI with water in water–acetone mixed solvent. Full conversion of IPDI to polymer is readily achieved thanks to the step polymerization mechanism involved. The monomer concentration can go up to 11wt.% with the polymerization accomplished within 2h, with a much higher yield of microspheres in a much shorter time than those reported with vinyl monomers. The size of the microspheres is adjustable by changing IPDI concentration, acetone/H2O ratio in the solvent or polymerization temperature. Without need of any stirring or shaking during the polymerization, the protocol renders the fabrication of uniform microspheres more practical and economical, particularly for large scaled production.

Efficient decolorization and deproteinization using uniform polymer microspheres in the succinic acid biorefinery from bio-waste cotton (Gossypium hirsutum L.) stalks

Bio-waste cotton (Gossypium hirsutum L.) stalks were converted into succinic acid by simultaneous saccharification and fermentation (SSF) using Actinobacillus succinogenes 130Z. After 54h SSF at 40°C and pH 7.0, the production of succinic acid was 63g/L, with 1.17g/L/h productivity and 64% conversion yield. After SSF, a simple method for the decolorization and deproteinization of crude SSF broth was developed through adsorption tests of polystyrene (PSt) microspheres. Under optimized conditions (5% PSt loading (w/v), pH 4.0, 60°C and adsorption time of 40min), the ratios of decolorization, deproteinization and succinic acid loss ratios were 96.6, 84.5 and 4.1%, respectively. The method developed will provide a potential approach for large-scale production of succinic acid from the biomass waste.

Preparation and Formation Mechanism of Uniform Polymer Microspheres in Precipitation Polymerization of Pentaerythritol Triacrylate and Styrene

Uniform polymer microspheres were prepared through precipitation polymerization of pentaerythritol triacrylate(PETA)and styrene in ethanol or an ethanol-water mixture using azobisisobutyronitrile(AIBN)as initiator.The effects of the polymerization time,amount of PETA,and water content in the mixed solvent on the polymerization process and the microspheres were studied. Uniform microspheres were readily obtained when the amount of PETA was between 5%and 35% (mass fraction)relative to all monomers with a polymerization time of 6h.When the mass fraction of PETA was20%,the microspheres decreased in size and became more uniform as the PETA mass fraction increased.By contrast,when the PETA mass fraction was20%,the microspheres size increased and the size distribution became larger as the PETA mass fraction increased.With the ethanol-water binary solvent mixture,the monomer conversion and microsphere yield increased compared with those obtained with pure ethanol.However,the water volume fraction needed to be kept below 30%,above which the uniformity of the microspheres was deteriorated.Based on the results,the mechanism of microsphere formation is discussed.

A novel protocol for the preparation of uniform polymer microspheres with high yields through step polymerization of isophorone diisocyanate

AbstractUniform polymer microspheres with neat surface are of high interests. Precipitation polymerization of vinylic monomers remains a very limited process owing to very low monomer concentration allowed. Here, a fully novel protocol for the production of uniform polymeric microspheres is presented. Using one single monomer, isophorone diisocyanate, highly monodisperse polyurea microspheres were achieved with very high yield in a very short time period via precipitation polymerization in water–acetone mixed solvent. Results demonstrated that the ratio of water–acetone and polymerization temperature played important roles in the process. The size of the microspheres was readily adjustable by varying monomer concentration, water/acetone ratio or polymerization temperature. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

Uniform poly(vinyl acetate) particles by radiation-induced dispersion polymerization in polar media

Micron-sized poly(vinyl acetate) particles were produced directly by radiation-induced dispersion polymerization in aqueous alcohol media using poly(N-vinylpyrrolidone) (PVP) as a steric stabilizer at room temperature. This method takes advantages of the specialities of radiation-induction, and highly uniform polymer microspheres were obtained. The effects of stabilizer content and medium polarity on the particle size and the size distribution were investigated. Based on the experimental results and radiation grafting theory, the stabilization mechanisms were discussed primarily.

Synthesis and characterization of crosslinked uniform polymeric microspheres containing a polyimide prepolymer by a new emulsification process

AbstractA highly crosslinked poly(styrene–divinyl benzene–trimethyolpropane trimethacrylate) microsphere containing a polyimide prepolymer (PIP) was prepared by a new emulsification method, Shirasu porous glass (SPG) membrane emulsification, and a subsequent radical suspension polymerization. That is, a mixture of styrene, divinyl benzene, trimethyol propane trimethacrylate (TMPTMA), and PIP containing an initiator was permeated through the uniform pores of the SPG membrane into a continuous phase containing a stabilizer to form uniform droplets. Then, the suspension polymerization was carried out at 65 °C for 24 h. The trifunctional crosslinker TMPTMA was added to enhance the destructive strength of the microsphere, and PIP was incorporated into the microsphere to provide an adhesion force by a known self‐curing reaction at 220 °C. The effects of the feed amounts of TMPTMA and PIP on the monomer conversion, size distribution, and destructive strength of the microsphere were investigated. The monomer conversion increased with an increase in TMPTMA. The particle size distribution became narrower as the TMPTMA feed amount increased, but it became broader with an increase in PIP. The destructive strength increased with increases in TMPTMA and PIP. After a heat treatment at 220 °C, the destructive strength decreased because of the heat degradation of the polymer. The addition of TMPTMA suppressed the heat degradation, and PIP could undergo self‐curing at 220 °C. The obtained highly crosslinked uniform microsphere containing PIP has potential applications in liquid‐crystal displays. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2588–2598, 2003

Formation of monodisperse poly(methyl methacrylate) particles by radiation-induced dispersion polymerization. II. Particle size and size distribution

Micron-sized poly(methyl methacrylate) particles were produced directly by radiation-induced dispersion polymerization in aqueous alcohol media using poly(N-vinylpyrrolidone) as a steric stabilizer at room temperature(10–35 °C). This method takes advantages of the specialities of radiation induction, and highly uniform polymer microspheres were obtained with high conversion. The gel effect was found from the polymerization kinetics curves. The number of nuclei produced in the early stage of the polymerization was found to be constant during the remainder of the polymerization. The effects of various polymerization parameters, such as irradiation dose rate, monomer concentration, stabilizer content, medium polarity, and polymerization temperature, on the particle size and the size distribution were investigated systematically.

Formation of Monodisperse Polyacrylamide Particles by Radiation-Induced Dispersion Polymerization: Particle Size and Size Distribution

Polyacrylamide microparticles were directly produced by radiation-induced dispersion polymerization in aqueous alcohol media using poly( N-vinylpyrrolidone) as a steric stabilizer at room temperature. The hydrodynamic diameter of a polymer particle and its distribution were measured on a dynamic laser light-scattering spectrometer. This method takes advantages of the specialities of radiation induction, and highly uniform polymer microspheres were obtained with high conversion. The number of the particle produced in the early stage of the polymerization was found to be constant during the remainder of the polymerization. The effects of various polymerization parameters, such as absorbed dose rate, monomer concentration, stabilizer content, medium polarity, and polymerization temperature on the particle size and size distribution were systematically investigated.

A Comparison of Membrane Emulsification Obtained Using SPG (Shirasu Porous Glass) and PTFE [Poly(Tetrafluoroethylene)] Membranes

ABSTRACT SPG (Shirasu porous glass) membrane emulsification used to prepare uniform polymeric microspheres is briefly reviewed, and the performance of a hydrophilically treated PTFE [poly(tetrafluoroethylerie)] membrane is described and compared with that of the SPG membrane. A mixture of styrene. divinyl benzene and hexadecane (HD) was extruded through the membranes and dispersed in an aqueous phase containing polyvinylalcohol (PVA) and sodium lauryl sulfate (SLS) as mixed stabilizers. A hvdrophilically treated PTFE membrane was used with a stainless steel mesh support so that the membrane would not expand to affect the pore size during the emulsification. The nominal pore size of the PTFE membrane was replaced with the calculated one using a theoretical expression derived from the force balance between the external pressure and the interfacial tension between oil and water phases. The emulsion droplets prepared with the PTFE membrane revealed a broader size distribution than those obtained with the SPG membrane, and the rate of emulsificaton was nearly same for both membranes. Droplet size control was readily possible. The performance was significantly affected by the adsorption behavior of the stabilizers on the membrane surfaces. The contact angle profile of oil droplets on the PTFE membrane implied that the hydrophilically treated PTFE membrane is still hydrophobic compared to the SPG membrane. This tendency was reflected by the dependence of the average droplet diameter (and coefficient of variation, CV) on the concentration and composition of mixed stabilizers.

?Continuous? emulsifier-free emulsion polymerization for the synthesis of monodisperse polymeric latex particles

A continuous emulsifier-free emulsion copolymerization (CEFEP) of styrene and divinylbenzene (DVB) or methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) has been devised to produce uniform polymeric microspheres of narrow size distribution from 74 nm to 2 μm, depending on reaction time. Monomer and crosslinker vapors were fed continuously into a small reactor. We suggest that after initial nucleation, subsequent CEFEP proceeds near the surfaces of growing particles in a monomer-swollen outer shell.

Synthesis of monodisperse polymeric microspheres including polyimide prepolymer by using SPG emulsification technique

An occlusion of a functional material, polyimide prepolymer (PIP), into uniform polymeric microspheres was attempted in order to demonstrate the versatility of the SPG (Shirasu porous glass) membrane emulsification technique. An oil phase consisting of hydrophobic monomers (styrene and acrylates with a longer side chain) and, although not necessarily, a water-insoluble reagent (lauryl alcohol) dissolved PIP up to 50 wt.%, and also an initiator (ADVN). An aqueous phase contained polyvinyl alcohol (PVA) and a small amount of sodium lauryl sulfate (SLS) as a stabilizing pair. The former was permeated through a SPG membrane, and uniform droplets were suspended in the latter. The seed droplets were swollen with the hydrophilic components, MMA and EGDMA, with a selective addition of isoamyl acetate, hexanol or octanol. After the swelling, an additional amount of the stabilizer solution was added. Polymerization was carried out at 343 K for 24 h. Uniform polymeric spheres, the coefficient of variation approximately 10% and occluding a maximum 28.4 wt.% of PIP were obtained. The entrapment of PIP was improved when the matrix polymer chains were crosslinked with EGDMA (but not with DVB), and an employment of the acrylates with a longer side chain, implying that the presence of ester groups are favored for a stable occlusion. A co-monomer system composed of MMA, 2-ethylhexyl acrylate and butyl acrylate plus octyl alcohol was able to occlude almost 100% of PIP in a stable condition without the presence of EGDMA.

Preparation of uniform poly(lactide) microspheres by employing the Shirasu Porous Glass (SPG) emulsification technique

Relatively uniform biodegradable poly(lactide) (PLA) microspheres were prepared by employing a Shirasu Porous Glass (SPG) membrane emulsification technique. Poly(lactide) dissolved in co-surfactant (hydrophobic substance)/dichloromethane (DCM) was used as a dispersed phase (oil phase) and an aqueous phase containing poly(vinyl alcohol) (PVA) and sodium lauryl sulfate (SLS) was used as a continuous phase. The oil phase permeated through the uniform pores of the SPG membrane into the continuous phase by a pressure of nitrogen gas to form the droplets. Then, the solid polymer microspheres were obtained by simply evaporating DCM at room temperature for 24 h. The effects of the type and the amount of the co-surfactant, and PLA concentration on the size, size distribution, and the morphologies of the droplets and particles were investigated. A relatively uniform spherical PLA microsphere was obtained successfully by using lauryl alcohol (LOH) rather than hexadecane (HD) as a co-surfactant. PLA concentration was varied from 10 to 20 wt.%/vol., and the LOH/DCM ratio changed from 0.5:11.5 to 2:10 by volume. At the polymer concentration range used in this study (10–20 wt.%), variation of the droplet size was not so apparent when 2 ml of LOH was used, but the droplet size showed a minimum value at 15 wt.% when 0.5 or 1 ml of LOH was used. The variation of CV value (coefficient of variation) was smaller in the PLA concentration range of 10–15 wt.%, then the CV value became larger as the PLA concentration was increased from 15 to 20 wt.%. Although there was a tendency that the droplet size and the CV value decreased as the LOH/DCM ratio increased, the CV value of the particle after the evaporation of DCM showed the lowest value when the amount of LOH was 1 ml (LOH/DCM=1:11, by vol.). Therefore it was most adequate to use 1 ml of LOH to prepare the particles with a relatively narrow size distribution. Furthermore, it was clarified that the phase-separation between PLA and LOH was apparent and the surface of the particle obtained was wrinkled when the PLA concentration was lower after DCM was evaporated, while the particles with the smooth surface were obtained when the PLA concentration was higher. This method provides a unique technique to prepare uniform polymer microspheres composed of natural polymers, bio-degradable polymers, co-polymers or polymer blends, polyesters and those which can not be polymerized by the radical polymerization.