Monodispersed thermoresponsive hydrogel microspheres with a volume phase transition driven by hydrogen bonding

We report the synthesis and characterization of monodispersed thermoresponsive hydrogel microspheres with a volume phase transition driven by hydrogen bonding. The prepared microspheres, composed of poly(acrylamide-co-styrene) (poly(AAM-co-St)) cores and poly(acrylamide)/poly(acrylic acid) (PAAM/PAAC) based interpenetrating polymer network (IPN) shells, were featured with high monodispersity and positively thermoresponsive volume phase transition characteristics with tunable swelling kinetics, i.e. the particle swelling was induced by an increase rather than a decrease in temperature. The monodisperse poly(AAM-co-St) seeds were prepared by emulsifier-free emulsion polymerization, the PAAM or poly(acrylamide-co-butyl methacrylate) (poly(AAM-co-BMA)) shells were fabricated on the seeds by free radical polymerization, and the core-shell microspheres with PAAM/PAAC based IPN shells were finished by a method of sequential IPN synthesis. The microsphere size increased with increasing both AAM and BMA dosages. The increase of hydrophilic monomer AAM dosage resulted in a better monodispersity, but the increase of hydrophobic monomer BMA dosage led to a worse monodispersity. With increasing the crosslinker methylenebisacrylamide (MBA) dosage, the mean diameter of the microspheres decreased and the monodispersity became better. An equimolar composition of AAC and AAM in the IPN shells of the microspheres resulted in a more complete shrinkage for the microspheres at temperatures lower than the upper critical solution temperature. Both BMA and MBA additions depressed the swelling ratio of the hydrodynamic diameter of the microspheres.     

Preparation of poly[dl-lactide-co-glycolide]-based microspheres containing protein by use of amphiphilic diblock copolymers of depsipeptide and lactide having ionic pendant groups as biodegradable surfactants by W/O/W emulsion method

To develop the preparative method for poly(dl-lactide-co-glycolide)-based microspheres containing proteins, we prepared microspheres from mixture of poly(dl-lactide-co-glycolide) and polydepsipeptide-block-poly(dl-lactide) having cationic or anionic pendant groups. Since the latter amphiphilic copolymers consisting of hydrophobic poly(dl-lactide) segment and hydrophilic polydepsipeptide segment with amino or carboxyl groups could be converted to cationic or anionic block copolymers, they could act as biodegradable surfactants on the preparation of poly(dl-lactide-co-glycolide)-based microspheres by water-in-oil-in-water emulsion method. The amphiphilic block copolymers were established to stabilize primary emulsions on the preparation of microspheres by scanning electron microscopy. We investigated the effects of the addition of the block copolymers on the entrapment efficiency of protein, the release behavior of protein from microspheres and the stability of protein.     

Preparation of narrow‐disperse or monodisperse poly{[poly(ethylene glycol) methyl ether acrylate]‐co‐(acrylic acid)} microspheres with ethyleneglycol dimethacrylate as crosslinker by distillation precipitation polymerization

Narrow‐disperse or monodisperse poly{[poly(ethylene glycol) methyl ether acrylate]‐co‐(acrylic acid)} (poly(PEGMA‐co‐AA)) microspheres were prepared by distillation precipitation polymerization with ethyleneglycol dimethacrylate (EGDMA) as crosslinker with 2,2′‐azobisisobutyronitrile as initiator in neat acetonitrile in the absence of any stabilizer, without stirring. The diameters of the resultant poly(PEGMA‐co‐AA‐co‐EGDMA) microspheres were in the range 200–700 nm with a polydispersity index of 1.01–1.14, which depended on the comonomer feed of the polymerization. The addition of the hydrogen bonding monomer acrylic acid played an essential role in the formation of narrow‐disperse or monodisperse polymer microspheres during the polymerization. Copyright © 2006 Society of Chemical Industry     

Poly(aspartic acid) surface modification of macroporous poly(glycidyl methacrylate) microspheres

Novel macroporous, hydrophilic microspheres with a surface layer of crosslinked poly(aspartic acid) were synthesized. In this study, macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) [poly(GMA-co-EGDMA)] microspheres with pore size around 370 nm were first obtained through the surfactant reverse micelle swelling method, and the poly(GMA-co-EGDMA) was aminated by ethylene diamine to form poly(GMA-NH₂). The polysuccinimide was grafted onto the surface of poly(GMA-NH₂) microspheres and crosslinked by hexamethylendiamine and γ-aminopropyltriethoxysilane, respectively, and then hydrolyzed to obtain the poly(aspartic acid)-functionalized macroporous microspheres. The functionalized hydrophilic microspheres were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis, mercury porosimetry, and elemental analysis. The metal ion adsorption capacity was also studied. The FTIR, XPS, and elemental analysis confirmed the poly(aspartic acid) functionalization of the poly(GMA-co-EGDMA) microspheres. SEM and mercury porosimetry showed there was little effect of this surface chemical modification on microsphere porosity, and the obtained macroporous microspheres exhibited excellent thermal stability and adsorption for Ag(I), presenting great potential for applications in adsorption, fixation, and separation. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47441.     

Effect of Basic Factors of Preparation on Characteristics,Hydrolytic Degradation,and Drug Release From Poly(ester-anhydride) Microspheres

Functional poly(ester-anhydride) microspheres were prepared using emulsion solvent evaporation (ESE) and phase inversion methods (PIM). The poly(ester-anhydride)s were obtained by polycondensation of sebacic acid (SBA) and oligo(3-allyloxy-1,2-propylene succinate) terminated with carboxyl groups (OSAGE). The effects of various parameters, including: polymer and emulsifier concentrations, stirring speed and molecular weight of polyvinyl alcohol (PVA) used as emulsifier on size, size distribution and morphology of microspheres obtained by ESE technique were examined. The size of microspheres obtained was in the range 2–30 µm and depended mainly on the stirring rate in emulsion formulation process, as well as concentration of polymer solution used. Molecular weight of PVA, and its concentration in aqueous phase, significantly influenced tendency to agglomeration of microparticles formed, but only slightly changed the size of microspheres. The present study demonstrated that the ESE method can be useful to formulate, from functional poly(ester-anhydride)s, small (2–3 µm) or large (20–30 µm) microspheres with relatively narrow size distribution. Such microspheres were loaded with three model compounds (rhodamine B, p-nitroaniline, and piroxicam) with different water solubility and their release characteristics were examined. In the present study microparticles were also obtained by alternative phase inversion method to compare mainly stability of polymers during formulation of microspheres by both techniques.     

Synthesis and characterization of air‐stable magnetic Fe composites microspheres of narrow size distribution

Air‐stable Fe magnetic nanoparticles entrapped within carbon and porous crosslinked polystyrene microspheres of narrow size distribution were prepared by the following sequential steps: (1) Polystyrene/poly(divinyl benzene) and polystyrene/poly(styrene‐divinyl benzene) uniform micrometer‐sized composite particles were prepared by a single‐step swelling of uniform polystyrene template microspheres dispersed in an aqueous continuous phase with emulsion droplets of dibutyl phthalate containing the monomers divinyl benzene and styrene and the initiator benzoyl peroxide. The monomers within the swollen polystyrene template microspheres were then polymerized by raising the temperature to 73°C; (2) Porous poly (divinyl benzene) and poly(styrene‐divinyl benzene) uniform crosslinked microspheres were prepared by dissolution of the polystyrene template part of the former composite particles; (3) Uniform magnetic poly(divinyl benzene)/Fe and poly(styrene‐divinyl benzene)/Fe composite microspheres were prepared by entrapping Fe(CO)₅ within the porous crosslinked microspheres, by suction of the Fe complex into the dried porous particles, followed by decomposition of the encapsulated Fe(CO)₅ at 200°C in Ar atmosphere; (4) Uniform magnetic air‐stable C/Fe composite microspheres were prepared similarly, apart from changing the decomposition temperature from 200 to 600°C. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Preparation of polymer/silica/polymer tri-layer hybrid materials and the corresponding hollow polymer microspheres with movable cores

Tri-layer poly(methacrylic acid-co-ethyleneglycol dimethacrylate)/silica/poly(ethyleneglycol dimethacrylate) (P(MAA-co-EGDMA)/SiO₂/PEGDMA) and P(MAA-co-EGDMA)/SiO₂/polydivinylbenzene hybrid microspheres were prepared by distillation precipitation polymerization of ethyleneglycol dimethacrylate (EGDMA) and divinylbenzene (DVB) in the presence of 3-(methacryloxy)propyl trimethoxysilane (MPS)-modified P(MAA-co-EGDMA)/SiO₂ microspheres as the seeds. The polymerization of EGDMA and DVB was performed in neat acetonitrile with 2,2′-azobisisobutyronitrile (AIBN) as initiator to coat the MPS-modified P(MAA-co-EGDMA)/SiO₂ seeds through the capture of EGDMA and DVB oligomer radicals with the aid of vinyl groups on the surface of modified seeds in the absence of any stabilizer or surfactant. Monodisperse P(MAA-co-EGDMA)/SiO₂ core-shell microspheres were synthesized by coating of a layer of silica onto P(MAA-co-EGDMA) microspheres via a sol-gel process, which were further grafted by MPS incorporating the reactive vinyl groups onto the surface to be used as the seeds for the construction of hybrid microspheres with tri-layer structure. Hollow poly(ethyleneglycol dimethacrylate) (PEGDMA) and poly(divinylbenzene) (PDVB) microspheres with movable P(MAA-co-EGDMA) core were subsequently developed after the selective etching of the silica mid-layer from the tri-layer hybrid microspheres in hydrofluoric acid. The morphology and structure of the tri-layer polymer hybrids and the corresponding hollow polymer microspheres with movable P(MAA-co-EGDMA) core were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectra and X-ray photoelectron spectroscopy (XPS).     

Effects of the process parameters on the initial burst release of poly(lactide‐co‐glycolide) microspheres containing bovine serum albumin by the double‐emulsion solvent evaporation/extraction method

The effects of fabrication parameters on the morphology, drug loading, and initial burst release of poly(lactide‐co‐glycolide) microspheres loaded with bovine serum albumin were investigated to establish an optimal process and system for the in vivo delivery of therapeutic proteins. Through the addition of salts or sugars to induce an osmotic pressure in the external water phase, large microspheres were seen to have their morphology, drug loading, and initial burst release significantly affected. However, the effect was not observed for compact microspheres less than 10 μm in diameter. The presence of poly(vinyl alcohol), Pluronic F127, and Tween 80 in the internal water phase had detrimental effects on the drug loading because of the depressed stability of the primary emulsion and competitive interactions of surface‐active substances with the polymer. However, the simultaneous addition of salts to the external water phase resulted in enhanced drug loading and decreased initial burst. The polymer concentration and volume of the internal water phase were important factors influencing the characteristics of the microspheres. These parameters were optimized for achieving the maximal drug loading and a low initial burst. The solvent extraction method yielded microspheres with a higher drug loading and a lower initial burst in comparison with the solvent evaporation method. Different ranges of protein encapsulation efficiencies were obtained with blends of poly(lactide‐co‐glycolide) and poly(ethylene glycol), depending on the molecular weight and content of poly(ethylene glycol). © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

包覆多层聚电解质/树状大分子的聚合物微球表面CdS纳米粒的形成

将聚酰胺-胺(PAMAM)树形大分子、聚对苯乙烯磺酸钠(PSS)和聚二烯丙基二甲基氯化铵(PDADMAC)在三聚氰胺甲醛(MF)微球上进行静电自组装,制得聚电解质壳层的核壳式微球. 通过反应沉积吸附方法生成具有稳定荧光性能的CdS/聚电解质核壳式复合微球. 用透射电镜表征复合微球形貌,用反射紫外和荧光表征了CdS/聚电解质核壳式复合微球的光学特性.     

Immobilization of glucoamylase on the plain and on the spacer arm‐attached poly(HEMA‐EGDMA) microspheres

Immobilization glucoamylase onto plain and a six‐carbon spacer arm (i.e., hexamethylene diamine, HMDA) attached poly(2‐hydroxyethylmethacrylate‐ethyleneglycol dimethacrylate) [poly(HEMA‐EGDMA] microspheres was studied. The microspheres were prepared by suspension polymerization and the spacer arm was attached covalently by the reaction of carbonyl groups of poly(HEMA‐EGDMA). Glucoamylase was then covalently immobilized either on the plain of microspheres via CNBr activation or on the spacer arm‐attached microspheres via CNBr activation and/or using carbodiimide (CDI) as a coupling agent. Incorporation of the spacer arm resulted an increase in the apparent activity of the immobilized enzyme with respect to enzyme immobilized on the plain of the microspheres. The activity yield of the immobilized glucoamylase on the spacer arm‐attached poly(HEMA‐EGDMA) microspheres was 63% for CDI coupling and 82% for CNBr coupling. This was 44% for the enzyme, which was immobilized on the plain of the unmodified poly(HEMA‐EGDMA) microspheres via CNBr coupling. The K_m values for the immobilized glucoamylase preparations (on the spacer arm‐attached microspheres) via CDI coupling 0.9% dextrin (w/v) and CNBr coupling 0.6% dextrin (w/v) were higher than that of the free enzyme 0.2% dextrin (w/v).The temperature profiles were broader for both immobilized preparations than that of the free enzyme. The operational inactivation rate constants (k_iop) of immobilized enzymes were found to be 1.42 × 10^?5 min^?1 for CNBr coupled and 3.23 × 10^?5 min^?1 for CDI coupled glucoamylase. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2702–2710, 2001     

Synthesis and characterization of uniform polyepoxide micrometer sized particles by redox graft polymerization of glycidyl methacylate on oxidized polystyrene and polydivinylbenzene microspheres for enzyme immobilization

Polystyrene template microspheres of narrow size distribution were prepared by dispersion polymerization of styrene in 2-methoxyethanol. Uniform polystyrene/poly(divinyl benzene) composite microspheres were formed by a single-step swelling process of the polystyrene template microspheres with dibutyl phthalate droplets containing divinyl benzene and benzoyl peroxide, followed by polymerization at 73 °C. Uniform poly(divinyl benzene) microspheres of higher surface area were produced by dissolution of the template polystyrene part of the former composite microspheres with methylene chloride. Hydroperoxide conjugated polystyrene and poly(divinyl benzene) microspheres were produced by controlled ozonolysis of these microspheres. Polyepoxide conjugated microspheres were then formed by redox graft polymerization of glycidyl methacylate on the hydroperoxide-conjugated microspheres. Microspheres with different properties, e.g., size, size distribution, shape, surface morphology, surface area, etc., have been prepared by changing various parameters belonging to the ozonolysis and the grafting polymerization processes, e.g., ozonolysis conditions and monomer volume. Trypsin was then covalently bound to the polyepoxide conjugated microspheres by interacting the epoxide groups of the particles with primary amino groups of the enzyme. A comparison between the enzymatic activity of the conjugated and the free trypsin was also established.     

Carbonization of PAN grafted uniform crosslinked polystyrene microspheres

Micrometer-sized polystyrene/poly(styrene-divinylbenzene) and polystyrene/polydivinylbenzene composite particles of narrow size distribution were formed by a single-step swelling process of uniform polystyrene template particles with emulsion droplets of dibutyl phthalate containing benzoyl peroxide and divinylbenzene in the presence or absence of styrene, followed by polymerization of the monomer(s) within the swollen template particles at 70 °C. Porous poly(styrene-divinylbenzene) and polydivinylbenzene uniform microspheres were formed by dissolution of the polystyrene part of the former composite particles. Hydroperoxide conjugated microspheres were formed by ozonolysis of the former porous microspheres. Uniform poly(styrene-divinylbenzene)/PAN and polydivinylbenzene/PAN core/shell microspheres were prepared by room temperature redox graft polymerization of AN onto the hydroperoxide conjugated particles. Uniform carbon microspheres were prepared by carbonization of the core/shell particles at 800 and 1100 °C under dynamic N₂ atmosphere. On the other hand, a similar treatment of the core particles only resulted in destruction of the particle shape. Carbon microspheres of increasing surface area (up to ca. 1000 m²/g) were prepared by activation of the former carbon microspheres with CO₂ at 850 °C. The influence of the carbonization temperature of the core/shell particles and the activation time of the carbon particles on the carbon yield and surface area has been elucidated.     

Synthesis of silver/polymer colloidal composites from surface-functional porous polymer microspheres

This study presents a different colloidal silver (Ag)/polymer system where Ag nanoparticles are deposited uniformly onto surface-functional porous poly(ethylene glycol dimethacrylate-co-acrylonitrile) (poly(EGDMA-co-AN)) microspheres. The formation and morphology of the composite microspheres were characterized from electron microscopy and X-ray diffraction analyses. The significance of the present report is that owing to the high affinity between Ag and nitrile group (CN) on the large surface of the microspheres, the Ag nanoparticles having a face-centered cubic phase were incorporated evenly into the deep pores of the microspheres with fine size and size distribution. In the preservation test, the Ag/poly(EGDMA-co-AN) composite microspheres obtained showed an excellent anti-bacterial performance, elucidating a high applicability for a new preservative.     

Modified poly(L-lactic acid) microspheres with nanofibrous structure suitable for biomedical application

Aminolyzed poly(L-lactic acid) (EPLA) microspheres with nanofibrous structure were prepared for the first time by aminolysis combined with emulsion and thermally induced phase separation technique from a ternary ethylenediamine aqueous solution/poly(L-lactic acid) (PLLA)-dioxane/propanetriol system. The results indicated that ethylenediamine concentration, aminolyzing time, and ratio of dioxane to ethylenediamine in aqueous solution significantly influenced the morphology and structures of microspheres. Under optimum conditions, monodispersed microspheres with nanofibrous structure were obtained. The in vitro bioactivity test showed that EPLA nanofibrous microspheres exhibited a strong apatite-formation ability compared with unmodified PLLA microspheres without nanofibrous structure, indicating that the bioactivity of PLLA microspheres was significantly improved through aminolysis reaction with ethylenediamine.     

Facile fabrication of highly conductive poly (styrene-co-methacrylic acid)/ poly(aniline) microspheres based on surface carboxylation modification

Fabrication of highly conductive poly(styrene)/poly(aniline) (PS/PANI) microspheres has been considerably explored. Improving the adsorption efficiency of aniline on the PS microspheres is still a challenge by facile methods. To overcome this problem, poly(styrene-co-methacylic acid) (poly(St-co-MAA)) is firstly synthesized for capturing anilinium ions, and then the in-situ polymerization of aniline is implemented to obtain highly conductive poly(St-co-MAA)/PANI microspheres. The prepared poly(St-co-MAA) microspheres bearing an average particle size of 238 nm possess a low polymer dispersity index (PDI, 0.082) and high zeta-potential, which guarantee no agglomeration and deposition of microspheres latex after 30 days at room temperature. After the in-situ polymerization of aniline, the conductive disc based on poly(St-co-MAA)/PANI microspheres presents a superior electrical conductivity of 14.6 S m⁻¹ at an inferior PANI loading of 5.74 vol% and a relatively low electrical percolation threshold (EPT < 0.16 vol%). The results indicate that the carboxylic microspheres for preparing high polymer/PANI microspheres is effective. Meanwhile, poly(St-co-MAA)/PANI microspheres show a great potential in manufacture of conductive composites due to their excellent electrical conductivity.     

Preparation and characterization of comb type polymer coated poly(HEMA/EGDMA) microspheres containing surface-anchored sulfonic acid: Application in γ-globulin separation

Poly(2-hydroxyethyl methacrylate/ethylenglycol dimethacrylate), poly(HEMA/EGDMA) microspheres was prepared via suspension polymerization. After activation of the hydroxyl groups of poly(HEMA/EGDMA) by bromination, surface-initiated atom transfer radical polymerization (ATRP) of glycidylmethacrylate was conducted in dioxane/bipyridine mixture with CuBr as catalyst at 65 °C. The epoxy groups of the poly(glycidylmethacrylate) comb polymer were converted into sulfonic acid groups (as proton-exchange groups) with reaction of sodium sulfite. Synthesized microspheres were characterized by swelling studies, FT-IR spectroscopy, scanning electron microscopy (SEM) and elemental analysis. The microspheres were used as ion-exchange support for adsorption and purification of human γ-globulin (IgG). The maximum γ-globulin adsorption on the ion-exchange adsorbents was observed at between pH 5.0 and 6.0. The IgG adsorption onto the poly(HEMA/EGDMA) microspheres was negligible. The maximum amount of adsorbed γ-globulin was found to be 230.1 mg/g microspheres. The ion-exchange adsorbents allowed one-step separation of IgG from human plasma. The γ-globulin molecules could be repeatedly adsorbed and desorbed with this ion-exchange support without noticeable loss in their IgG adsorption capacity.     

In vitro degradation and release profiles of poly‐DL‐lactide‐poly(ethylene glycol) microspheres with entrapped proteins

Poly‐DL ‐lactide (PLA) and poly‐DL ‐lactide‐poly(ethylene glycol) (PELA) were produced by bulk ring‐opening polymerization using stannous chloride as initiator. PLA, PELA microspheres, and PELA microspheres containing the outer membrane protein (OMP) of Leptospira interrogans with the size of 1.5–2 μm were prepared by a solvent evaporation process. In vitro degradation and release tests of PLA, PELA, and OMP‐loaded PELA microspheres were performed in pH 7.4 buffer solution at 37°C. Quantitatively, the degree of degradation was monitored by detecting the molecular weight reduction, by evaluating the mass loss and the apparent degradation rate constant, and by determining the intrinsic viscosity and poly(ethylene glycol) content of retrieved polymer, while the release profile was assessed by measuring the amount of protein presented in the release medium at various intervals. Qualitatively, the morphological changes of microspheres were observed with scanning electron micrography. The observed relative rates of mass loss versus molecular weight reduction are consistent with a bulk erosion process rather than surface erosion for PELA microspheres. The introduction of hydrophilic poly(ethylene glycol) domains in copolymer PELA and the presence of OMP within microspheres show critical influences on the degradation profile. The OMP‐loaded PELA microspheres present triphasic release profile and a close correlation is observed between the polymer degradation and the OMP release profiles. It is suggested that the polymer degradation rate, protein diffusion coefficient, and the water‐swollen structure of microspheres matrix commonly contribute to the OMP release from PELA microspheres. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 140–148, 2000     

Congo red- and Zn(II)-derivatized monosize poly(MMA-HEMA) microspheres as specific sorbent in metal chelate affinity of albumin

Monosize poly(methylmethacrylate-hydroxyethylmethacrylate) [poly(MMA-HEMA)] microspheres (4 μm in diameter) were produced by dispersion copolymerization of MMA and HEMA in an ethanol-water medium. Congo Red was attached to the poly(MMA-HEMA) microspheres, covalently. These Congo Red-derivatized microspheres were characterized by optical microscopy, Fourier transform infrared spectroscopy, and elemental analysis. Then, Zn(II) ions were incorporated by chelating with the immobilized Congo Red molecules. Different amounts of Zn(II) ions [1.2–17.6 mg of Zn(II)/g of polymer] were conjugated on the microspheres by changing the initial concentration of Zn(II) ions and pH. Bovine serum albumin (BSA) adsorption on these microspheres from aqueous solutions containing different amounts of BSA at different pH and ionic strengths was investigated in batch reactors. The nonspecific BSA adsorption on the plain poly(MMA-HEMA) microspheres was very low (0.7 mg of BSA/g of polymer). Congo Red derivatization significantly increased the BSA adsorption (up to 35.8 mg of BSA/g of polymer). A further increase in the adsorption capacity (up to 61.0 mg of BSA/g of polymer) was observed when Zn(II) ions were incorporated. More than 90% of the adsorbed BSA was desorbed in 1 h in the desorption medium containing 1.0M NaSCN at pH 8.0. © 1997 John Wiley & Sons, Inc.     

Synthesis,characterization, and in vitro release of ibuprofen from poly(MMA‐HEMA) copolymeric core–shell hydrogel microspheres for biomedical applications

This article describes the development of a new crosslinked poly(methyl methacrylate‐2‐hydroxyethyl methacrylate) copolymeric core–shell hydrogel microsphere incorporated with ibuprofen for potential applications in bone implants. Initially poly(methyl methacrylate) (PMMA) core microspheres were prepared by free‐radical initiation technique. On these core microspheres, 2‐hydroxyethyl methacrylate (HEMA) was polymerized by swelling PMMA microspheres with the HEMA monomer by using ascorbic acid and ammonium persulfate. Crosslinking monomers such as ethylene glycol dimethacrylate (EGDMA) has also been included along with HEMA for polymerization. By this technique, it was possible to obtain core–shell‐type microspheres. The core is a hard PMMA microsphere having a hydrophilic poly(HEMA) shell coat on it. These microspheres are highly hydrophilic as compared to PMMA microspheres. The size of the hydrogel microspheres almost doubled when swollen in benzyl alcohol. These microspheres were characterized by various techniques such as optical microscopy, scanning electron microscopy, Fourier‐transformed infrared spectroscopy, thermogravimetric analysis, and differential scanning calorimetry. The particle size of both microspheres was analyzed by using Malvern Master Sizer/E particle size analyzer. The in vitro release of ibuprofen from both microspheres showed near zero‐order patterns. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 3045–3054, 2002; DOI 10.1002/app.10310     

Monodisperse temperature-responsive hollow polymer microspheres: Synthesis, characterization and biological application

Temperature-responsive hollow poly(N-isopropylacrylamide) (PNIPAAm) microspheres were prepared by a two-stage distillation precipitation polymerization to afford a core-shell microspheres with subsequent removal of poly(methacrylic acid) (PMAA) core. PMAA@PNIPAAm core-shell microspheres were synthesized by the second-stage polymerization of NIPAAm in the presence of PMAA as core with N,N′-methylenebisacrylamide as crosslinker in acetonitrile, in which the hydrogen-bonding interaction between the carboxylic acid group of PMAA core and the amide group of NIPAAm as well as MBAAm played a key role to form the core-shell microspheres. The hollow PNIPAAm microspheres with different thicknesses, which were controlled by the monomer loading level and the crosslinking degree, were developed after the removal of PMAA core. The loading and controlled-release behavior of the drug on the hollow PNIPAAm microspheres was investigated with doxorubicin hydrochloride. The core-shell and hollow microspheres were characterized with transmission electron microscopy, scanning electron microscopy, dynamic light scattering, static light scattering, X-ray photoelectron spectroscopy, elemental analysis, and FT-IR spectra.