Effects of the reaction parameters on the properties of thermosensitive poly(N‐isopropylacrylamide) microspheres prepared by precipitation and dispersion polymerization

Poly(N‐isopropylacrylamide) (PNIPAAm)‐based microspheres were prepared by precipitation and dispersion polymerization. The effects of several reaction parameters, such as the type and concentration of the crosslinker (N,N′‐methylenebisacrylamide or ethylene dimethacrylate), medium polarity, concentration of the monomer and initiator, and polymerization temperature, on the properties were examined. The hydrogel microspheres were characterized in terms of their chemical structure, size and size distribution, and morphological and temperature‐induced swelling properties. A decrease in the particle size was observed with increasing polarity of the reaction medium or increasing concentration of poly(N‐vinylpyrrolidone) as a stabilizer in the dispersion polymerization. The higher the content was of the crosslinking agent, the lower the swelling ratio was. Too much crosslinker gave unstable dispersions. Although the solvency of the precipitation polymerization mixture controlled the PNIPAAm microsphere size in the range of 0.2–1 μm, a micrometer range was obtained in the Shellvis 50 and Kraton G 1650 stabilized dispersion polymerizations of N‐isopropylacrylamide in toluene/heptane. Typically, the particles had fairly narrow size distributions. Copolymerization with the functional glycidyl methacrylate monomer afforded microspheres with reactive oxirane groups. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 968–982, 2006     

A thermosensitive amphoteric microsphere and its potential application as a biological carrier

Thermosensitive poly(N-isopropylacrylamide) moieties were introduced onto amphoteric styrene/glycidyl methacrylate copolymer seed microspheres prepared by use of amphoteric initiators. The resulting microspheres exhibited thermosensitive and amphoteric behavior, so dual sensitivity to both pH and temperature was observed. The colloidal properties of the microspheres before and after seeded polymerization were characterized by varying the temperature and the pH. The results indicated that the specific surface structure emerged when the environmental conditions were changed. In addition, the reactive epoxy groups on the microsphere surface could be utilized to immobilize the protein molecules. The behavior of protein adsorption and immobilization onto the microspheres was examined in order to understand their potential applications in biological areas.     

Superabsorbent poly(acrylamide-co-itaconic acid) hydrogel microspheres: Preparation,characterization and absorbency

Poly(acrylamide-co-itaconic acid) (P(AM-co-IA)) hydrogel microspheres were prepared via inverse suspension polymerization method. DLS results showed the formation of the monodispersed hydrogel microspheres. The size of the hydrogel microspheres could be controlled by polymerization parameters. Absorbencies of P(AM-co-IA) microspheres in water and saline were investigated and calculated by size changes of each particle before and after swelling. The results showed that P(AM-co-IA) had high absorbencies, the weight of swollen particles was above 4000 times to that of the original dried microspheres. The superabsorbent hydrogel microspheres might find the potential applications in the fields of soil amendments, water shutoff agents, and drug delivery carriers.     

Poly(N,N‐diethylacrylamide) microspheres by dispersion polymerization

Poly(N,N‐diethylacrylamide)‐based microspheres were prepared by ammonium persulfate (APS)‐initiated and poly(vinylpyrrolidone) (PVP)‐stabilized dispersion polymerization. The effects of various polymerization parameters, including concentration of N,N′‐methylenebisacrylamide (MBAAm) crosslinker, monomer, initiator, stabilizer and polymerization temperature on their properties were elucidated. The hydrogel microspheres were described in terms of their size and size distribution and morphological and temperature‐induced swelling properties. While scanning electron microscopy was used to characterize the morphology of the microspheres, the temperature sensitivity of the microspheres was demonstrated by dynamic light scattering. The hydrodynamic particle diameter decreased sharply as the temperature reached a critical temperature ～ 30 °C. A decrease in the particle size was observed with increasing concentration of both the APS initiator and the PVP stabilizer. The microspheres crosslinked with 2–15 wt % of MBAAm had a fairly narrow size distribution. It was found that the higher the content of the crosslinking agent, the lower the swelling ratio. High concentration of the crosslinker gave unstable dispersions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6263–6271, 2008     

Effect of reaction parameters on the dispersion polymerization of 1‐vinyl‐2‐pyrrolidone

Nonporous hydrogel microspheres 0.1–1.3 μm in diameter were prepared by the dispersion copolymerization of 1‐vinyl‐2‐pyrrolidone and ethylene dimethacrylate as a crosslinking agent. The crosslinking was evidenced by solid state ¹³C NMR and elemental analysis. The effect of various parameters including selection of solvent (cyclohexane, butyl acetate), initiator (4,4′‐azobis(4‐cyanopentanoic acid), 2,2′‐azobisisobutyronitrile, dibenzoyl peroxide) and stabilizer on the properties of resulting microspheres has been studied. Dynamic light scattering and photographic examination were used for determination of the diameter and polydispersity of microspheres. Increasing concentration of steric stabilizer in the initial polymerization mixture decreased the particle size. The particle size depended on the molecular weight of polystyrene‐block‐hydrogenated polyisoprene stabilizer, but not on the number of PS and polybutadiene blocks in the styrene–butadiene block copolymer stabilizers. Dibenzoyl peroxide used as an initiator resulted in agglomeration of particles. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 653–663, 2000     

Preparation of polyvinylpyrrodione microspheres by dispersion polymerization

The preparation of polyvinylpyrrolidone (PVP) microspheres in ethyl acetate by dispersion polymerization with N-vinylpyrrolidone (NVP) as initial monomer, poly(N-vinylpyrrolidone-co-vinyl acetate) (P (NVP-co-VAc)) as dispersant, and 2, 2′-azobisisobutyronitrile(AIBN) as initiator is reported. The influences of monomer concentration, dispersant concentration and initiator concentration on the size of PVP microspheres as well as the monomer conversion were studied. The structure and properties of PVP microspheres were analyzed. The results show that the prepared PVP microspheres have a mean diameter of 3-4 μm. With an increase in NVP concentration, the size and the molecular weight of the PVP microspheres as well as the monomer conversion all increase. With increasing P(NVP-co-VAc) concentrations, the PVP molecular weight and monomer conversion both increase while the size of the microspheres becomes smaller. As the concentration of AIBN increases, the microsphere size and monomer conversion increase whereas the PVP molecular weight decreases. The PVP prepared by dispersion polymerization has a crystal structure, and its molecular weight is lower compared to that prepared by solution polymerization. __________ Translated from Acta Polymerica Sinica, 2007, 11 (in Chinese)     

Mechanism of the formation of stable microspheres by precipitation copolymerization of styrene and divinylbenzene

Fully crosslinked, stable poly(styrene‐co‐divinylbenzene) microspheres were prepared by precipitation polymerization, and a new mechanism is proposed, based on the morphology, circularity, and specific surface area. Once the stable particles were generated by aggregation of the primary nucleus particles, they grew in size by absorbing oligomeric species without generating substantial pores. The investigation was carried out characterizing the particles in the polymerization time and in various concentrations of the polymerization ingredients. Particle size continuously grew, but the uniformity and circularity of the microspheres were reduced with polymerization time because of the higher reactivity of divinylbenzene. The measured specific surface areas of the microspheres all were less than 10 m²/g, which showed good agreement with calculated values under an assumption of no pores on the surface of the microspheres. Thus, the specific surface area of the microspheres supported the proposed mechanism. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3967–3974, 2004     

Graft copolymers having hydrophobic backbone and hydrophilic branches. XI. Preparation and thermosensitive properties of polystyrene microspheres having poly (N-isopropylacrylamide) branches on their surfaces

Thermosensitive microspheres with 0.4–1.2 μm diameter consisting of a polystyrene core and poly(N-isopropylacrylamide) (polyNIPAAm) branches on their surfaces were prepared by the free radical polymerization of a polyNIPAAm macromonomer and styrene in ethanol. Electron spectroscopy for chemical analysis (ESCA) of the microsphere surface suggested that polyNIPAAm chains were favorably located on the surface of the microspheres. The morphology of the microspheres was observed by transmission electron micrograph (TEM) and the particle size of was estimated by submicron particle analyzer. The molecular weight of the polyNIPAAm macromonomer, the ratio of the macromonomer and styrene, and the polymerization temperature affected the particle size. Thermosensitive properties of polyNIPAAm-coated polystyrene microspheres were evaluated by the turbidity of their dispersion solutions and the hydrodynamic size of the miocrospheres. The transmittance in dispersion solutions changed clearly, similar to oligoNIPAAm and polyNIPAAm macromonomers. In addition, the particle size of microspheres decreased with rising temperature. These results were explained by the thermosensitivity of polyNIPAAm branches on the microsphere surface. © 1996 John Wiley & Sons, Inc.     

Synthesis of highly monodisperse polystyrene microspheres via dispersion polymerization using an amphoteric initiator

The highly monodisperse polystyrene (PS) microspheres were produced by dispersion polymerization using an amphoteric initiator, 2,2'-azobis [N-(2-carboxyethyl)-2-2-methylpropionamidine] (VA-057). The polymerization characteristics were investigated and compared with conventional initiators, 2,2-azobis(isobutyronitrile) (AIBN) and benzoyl peroxide (BPO). The monodisperse PS microspheres having the coefficient of variation (C(v)) of diameter all less than 4% are obtained at very low stabilizer, poly(vinyl pyrrolidone) (PVP) concentrations of 1 and 2 wt%. It is found that the size dependence of the VA-057 system, D(n) proportional, variant [VA-057](0.267), is less sensitive than a conventional initiator system. When the same amount, 2 wt%, of AIBN, BPO, and VA-057 is used under the identical PVP concentration of 2 wt%, the D(n)/C(v)'s are 1.95/11.57, 1.47/22.44, and 2.08 microm/2.50%, respectively. The uniformity of particles was characterized employing an optical analyzer, Turbiscan. For the VA-057 system, the back scattering intensity is linearly reduced with time having a constant sedimentation rate of 48.98 microm/min throughout the settling process. The uniformity of PS particles in the VA-057 system stems from (1) the higher rate of polymerization in early stage of polymerization, followed by significantly faster reduction of the rate, and (2) good dispersion stability of primary particles. Therefore, it is found that the use of an amphoteric initiator, VA-057, is promising for producing monodisperse particles in dispersion polymerization.     

Monodisperse polystyrene microspheres prepared by dispersion polymerization with microwave irradiation

Monodisperse polystyrene microspheres with diameters of 200–500 nm were prepared by dispersion polymerization with microwave irradiation with poly(N‐vinylpyrrolidone) as a steric stabilizer and 2,2′‐azobisisobutyronitrile as a radical initiator in an ethanol/water medium. The morphology, size, and size distribution of the polystyrene microspheres were characterized with transmission electron microscopy and photon correlation spectroscopy, and the formed films of the polystyrene dispersions were characterized with atomic force microscopy. The effects of the monomer concentration, stabilizer concentration, and initiator concentration on the size and size distribution of the polystyrene microspheres were investigated. The polystyrene microspheres prepared by dispersion polymerization with microwave irradiation were smaller, more uniform, and steadier than those obtained with conventional heating. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2368‐2376, 2005     

A responsive poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate hydrogel microsphere

A responsive hydrogel microsphere, which is constituted by poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate, was fabricated in an aqueous two-phase system based on the polymer–polymer immiscibility. Characteristics of the hydrogel microsphere, such as the particle size and the morphology of freeze-dried or hydrated natural microspheres in water, tetrahydrofuran (THF)/H₂O (1:1 in volume) or acetone/H₂O (1:1 in volume), were investigated. The results showed that the swelling ratio and the particle size of the hydrogel microspheres were highly dependent on solvent composition. In addition, these characteristics were dramatically reduced when THF or acetone was added into the aqueous media. Scanning electron microscopy and environmental scanning electron microscopy micrographs also visually demonstrated that the regular spherical shape of the microspheres in water turned to irregular in shape when the microspheres were immersed in THF/H₂O or acetone/H₂O mixtures instead of pure water.     

用无乳化剂乳液聚合法制备聚丙烯醛微球

本文应用无乳化剂乳液聚合法合成了粒度均一、具有活泼醛基的聚丙烯醛微球,并对丙烯醛聚合动力学和影响微球直径,活泼醛基含量的因素进行了研究。用合成的微球同不同的氨基酸和午血清白蛋白反应,结果表明:该微球在生理pH条件下同含有伯氨基的化合物具有较高的结合容量。因此,在无乳化剂存在下,采用乳液聚合法制备聚丙烯醛微球是一种合成具有干净表面的聚丙烯醛微球的新方法。     

Synthesis and release profile analysis of thermo-sensitive albumin hydrogels

Novel thermo-responsive hydrophilic microspheres were prepared by free radical polymerization of methacrylate bovine serum albumin and N-isopropylacrylamide, as cross-linker and functional monomer, respectively. The incorporation of monomers in the network was confirmed by infrared spectroscopy, while the network density and shape of hydrogels strictly depend on concentration of monomers in the polymerization feed. The thermal analyses showed negative thermo-responsive behavior with pronounced water affinity of microspheres at temperature lower than lower critical solution temperature (LCST). The in vitro release studies of drug-loaded thermo-sensitive hydrogels were performed. Experimental data showed, for the copolymers with functional monomer/cross-linker ratio ≤ 1, a predominant drug release in the collapsed state, while the copolymers with functional monomer/cross-linker ratio > 1 showed prominent drug release in the swollen state. Below the hydrogel LCST, drug release through the swollen polymeric networks was observed, while a squeezing-out effect at temperature above the LCST was predominant.     

Effect of the polymerization parameters on the morphology and spherical particle size of poly(styrene-<Emphasis Type="Italic">co</Emphasis>-divinylbenzene) prepared by precipitation polymerization

Poly(styrene-co-divinylbenzene) microspheres having a diameter range of 3.0–4.5 µm were synthesized by precipitation polymerization under various conditions, then the effects of the polymerization parameters such as monomer and initiator concentration, and used cosolvents on the characteristics of the final particles were compared with those in dispersion polymerization. It was found that precipitation polymerization is more sensitive to polymerization conditions than dispersion polymerization, and that precise control of polymerization parameters is therefore essential for individually stable spherical particles. Monomer and initiator concentration, and the use of cosolvents significantly vary the morphology and the size of the final particles. However, the uniformity of the microspheres is not greatly affected by the polymerization parameters.     

Magnetic poly(N‐propargylacrylamide) microspheres: Preparation by precipitation polymerization and use in model click reactions

Magnetic poly(N‐propargylacrylamide) (PPRAAm) microspheres were prepared by the precipitation polymerization of N‐propargylacrylamide (PRAAm) in a toluene/propan‐2‐ol medium in the presence of magnetic nanoparticles (oleic acid‐coated Fe₃O₄). The effects of several polymerization parameters, including the polarity of the medium, polymerization temperature, the concentration of monomer, and the amount of magnetite (Fe₃O₄) in the polymerization feed, were examined. The microspheres were characterized in terms of their morphology, size, particle‐size distribution, and iron content using transmission and scanning electron microscopies (TEM and SEM) and atomic absorption spectroscopy (AAS). A medium polarity was identified in which magnetic particles with a narrow size distribution were formed. As expected, oleic acid‐coated Fe₃O₄ nanoparticles contributed to the stabilization of the polymerized magnetic microspheres. Alkyne groups in magnetic PPRAAm microspheres were detected by infrared spectroscopy. Magnetic PPRAAm microspheres were successfully used as the anchor to enable a “click” reaction with an azido‐end‐functionalized model peptide (radiolabeled azidopentanoyl‐GGGRGDSGGGY(¹²⁵I)‐NH₂) and 4‐azidophenylalanine using a Cu(I)‐catalyzed 1,3‐dipolar azide‐alkyne cycloaddition reaction in water. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011.     

Precipitation polymerization in acetonitrile and 1‐propanol mixture: synthesis of monodisperse poly(styrene‐co‐divinylbenzene) microspheres with clean and smooth surface

Precipitation polymerization of styrene (St)–divinylbenzene (DVB) has been carried out using acetonitrile/1‐propanol mixture as the reaction media and 2,2′‐azobisisobutyronitrile (AIBN) as initiator. Monodisperse micron‐sized poly(St‐co‐DVB) microspheres with clean and smooth surface were synthesized in the absence of any stabilizing agent such as surfactants or steric stabilizers. The effects of various polymerization parameters such as 1‐propanol fraction in the reaction media, initiator and total monomer concentration, DVB content, polymerization time and polymerization temperature on the morphology, particle size and size distribution were investigated. It was found that smoothly shaped stable particles were obtained when less than 70 vol% of 1‐propanol was used in the media. The particle size increased with the AIBN concentration, whereas the change of uniformity was less obvious. Monodisperse microspheres were obtained when the total monomers loading ranged from 0.5 to 3 vol%. The particle diameter ranged from 2.73 to 1.87 µm with an increasing DVB content and the uniformity was enhanced. In addition, the yield of microspheres increased with the increasing total monomer, initiator, and DVB concentration and polymerization time. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of freeze-drying and rehydrating treatment on the thermo-responsive characteristics of poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) microspheres

Investigations on the effect of freeze-drying and rehydrating treatment on equilibrium volume changes and on the thermo-response rate of poly(N-isopropylacrylamide) (PNIPAM) microspheres were carried out. The experimental results showed that freeze-drying and rehydrating treatment had nearly no effect on the low critical solution temperature and equilibrium volume changes of PNIPAM microspheres. Furthermore, when the PNIPAM microspheres were frozen in only liquid nitrogen through rapid cooling, the response rate of PNIPAM microspheres to environmental temperature change was nearly not affected by the treatment, which was surprisingly different from the macroscopic hydrogel. The dimension effect was responsible for this phenomenon. The micron-sized PNIPAM microsphere itself has a much quicker response rate compared with the bulky hydrogel because the characteristic time of gel deswelling is proportional to the square of a linear dimension of the hydrogel.     

Synthesis of polystyrene microspheres by dispersion polymerization in supercritical carbon dioxide using a poly(dimethylsiloxane)-based macroazoinitiator

The synthesis of polystyrene microspheres was achieved by the dispersion polymerization of styrene in supercritical carbon dioxide using azobisisobutylonitrile (AIBN) and a poly(dimethylsiloxane) (PDMS)-based macroazoinitiator, VPS-1001. VPS-1001 contained seven to nine molecules of the azo groups and the PDMS blocks with a molecular weight of 10,000 per molecule. The polymerization in the presence of both VPS-1001 and AIBN produced polystyrene microspheres with a diameter below 4 μm in over 85% yields, whereas the polymerization with VPS-1001 in the absence of AIBN provided a nonspecific polystyrene in only 20% yield. The particle size decreased as a result of increasing the concentration of VPS-1001. It was confirmed that the polystyrene particles were stabilized by the PDMS-block-polystyrene formed through the polymerization initiated by VPS-1001 because the polymerization using a PDMS homopolymer provided nonspecific polystyrene as a precipitate during the polymerization.     

Emulsifier-free emulsion copolymerization of styrene and acrylamide using an amphoteric initiator

Emulsifier-free emulsion copolymerization of styrene (St) and acrylamide (AAm) has been investigated in the presence of an amphoteric water-soluble initiator, 2,2′-azobis[N-(2-carboxyethyl)-2-2-methylpropionamidine]hydrate (VA057). The kinetics of polymerization and the colloidal properties of the resulting latices were studied and compared with the cases using ionic initiators. When adopting the amphoteric initiator at pHs lower than 10, stable amphoteric poly (St/AAm) latices, evidenced by the electrophoretic mobility, were prepared directly. Meanwhile, almost the same conversion versus time curves appeared and there were no apparent differences in the final particle sizes for those polymerizations, whereas in the polymerization at pH 10, a much lower rate of copolymerization and a larger size of particles were observed. The surface charge density and the growth rate of latex particles produced with VA057 at pH<10 were comparable to those of the particles with a cationic initiator, 2,2′-azobis(2-amidinopropane)dihydrochloride, but were apparently lower than those with an anionic initiator, potassium persulfate, when the polymerizations were carried out under corresponding conditions. The number of initiator fragments incorporated onto the particle surfaces was independent of polymerization pH, except for pH 10. The abnormal performance of VA057 at pH 10 was attributed to its degradation due to hydrolysis. Received: 14 December 1999 Accepted: 22 February 2000     

Poly(N,N‐dimethylacrylamide)‐Based Microspheres Prepared by Heterogeneous Polymerizations

PDMAAm microspheres have been obtained by inverse suspension, inverse emulsion, and dispersion polymerization. Conventional inverse suspension polymerization in toluene/trichloroethene is modified by the use of ultrasound. The resulting hydrogel microspheres are examined by dynamic light scattering and scanning electron microscopy to afford the morphology, dispersity, and size of the microspheres. Inverse suspension polymerization yields 100‐µm particles, while those obtained by inverse emulsion polymerization are 0.13–1 µm in diameter. While the inverse techniques produce particles of broad size distribution, monodisperse microspheres are obtained by the Kraton G 1650‐stabilized dispersion polymerization of DMAAm in a toluene/heptane medium. The particle size and polydispersity could be controlled by the addition of water into the dispersed phase, and by varying the cellulose acetate butyrate or Kraton G 1650 concentration and the toluene/trichloroethene or toluene/heptane ratio.