Research Progress on the Preparation of Inorganic/Natural Materials Composite Microspheres

Microspheres are a new type of drug carrier with great potential for development and application.Natural polymers have good biocompatibility,biodegradability,and are easily dispersed in living organisms,making them suitable for preparing microspheres.Inorganic materials(mainly inorganic minerals)have excellent mechanical properties and are inexpensive and easy to obtain.Through the coupling and hybridization of natural polymers and inorganic materials,they can complement each other's advantages and synergistically enhance efficiency,resulting in many excellent physical and chemical properties.Inorganic materials/natural polymer composite microspheres can be prepared by modifying natural polymers with inorganic materials through various methods such as emulsification crosslinking,solution mixing,in-situ synthesis,extrusion,etc.The application of inorganic materials/natural polymer composite microspheres in drug delivery systems has significant sustained-release effects,is safe and non-toxic,and the cost of carrier materials is relatively low,which has certain significance for the development of new drug carriers.This article reviews the recent research on the preparation,drug loading and release properties of inorganic material/natural polymer composite microspheres,analyzes the advantages and disadvantages of commonly used preparation methods,and looks forward to the development direction of composite microspheres.

SYNTHESIS OF MONODISPERSE HOLLOW POLYMER MICROSPHERES WITH FUNCTIONAL GROUPS BY DISTILLATION PRECIPITATION POLYMERIZATION

Monodisperse hollow polymer microspheres having various functional groups on the shell-layer, such as carboxylic acid, pyridyl and amide, were prepared by two-stage distillation precipitation polymerization in neat acetonitrile in the absence of any stabilizer or additive, during which monodisperse poly（methacrylic acid） （PMAA） afforded from the first-stage polymerization was utilized as the seeds for the second-stage polymerization. The shell layer with different functional groups was formed during the second-stage copolymerization of either divinylbenzene （DVB） or ethyleneglycol dimethacrylate （EGDMA） as crosslinker and the functional comonomers, in which the hydrogen-bonding interaction between the carboxylic acid group of PMAA core and the functional groups of the corresponding comonomers, including carboxylic acid, amide and pyridyl, played an essential role for the formation of monodisperse core-shell functional microspheres. The hollow polymer microspheres were then developed after the subsequent removal of PMAA cores by dissolution in ethanol under basic condition. Transmission electron microscopy （TEM） and scanning electron microscopy （SEM） were used to determine the morphology of the resultant PMAA core, functional core-shell microspheres and the corresponding hollow polymer microspheres with different functional groups. FT-IR spectra confirmed the successful incorporation of the various functional groups on the shell layer of the hollow polymer microspheres.

A review of recent progress in preparation of hollow polymer microspheres

The preparation methods of hollow polymer microspheres both at home and abroad are summarized, and their preparation mechanisms and developmental states are presented. These methods include the liquid droplet method, dried-gel droplet method, self-assembly method, microencapsulation method, emulsion polymerization method and the template method. Hollow polystyrene microspheres are the most extensively studied in the research of hollow polymer microspheres. Through comparison of the advantages and disadvantages of different preparation methods, it is concluded that microencapsulation method is most suitable for preparing polystyrene hollow microspheres.

PREPARATION OF MONODISPERSE CROSSLINKED POLYMER MICROSPHERES HAVING CHLOROMETHYL GROUP BY DISTILLATIONPRECIPITATION POLYMERIZATION

Monodisperse crosslinked poly(chloromethylstyrene-co-divinylbenzene)(poly(CMSt-co-DVB))microsphereswere prepared by distillation-precipitation copolymerization of chloromethylstyrene(CMSt)and divinylbenzene(DVB)inneat acetonitrile.The polymer particles had clean surfaces due to the absence of any added stabilizer.The size of the particlesranges from 2.59 μm to 3.19 μm and with mono-dispersity around 1.002-1.014.The effects of monomer feed incopolymerization on the microsphere formation were described.The polymer microspheres were characterized by SEM andchlorinity elemental analysis.

Porous polymer microsphere functionalized with benzimidazolium based ionic liquids as effective solid catalysts for esterification

To prepare polymer supported ionic liquids(PSILs)as effective catalysts for esterification,the free radical suspension copolymerization of vinylbenzyl chloride(VBC,monomer),styrene(St,monomer)and divinylbenzene(DVB,crosslinker)with the addition of n-heptane(porogen)was carried out for the fabrication of the porous polymer(PVD)microsphere as support,followed by the immobilization of sulfonic acid-functionalized ionic liquids by the successive treatment of benzimidazole(BIm),1,3-propane sultone and sulfuric acid(H2SO4)or trifluoromethanesulfonic acid(CF3SO3H).The effects of the compositions of DVB and n-heptane on the internal structure of the polymer supports were investigated,and it was found that the support with 40 wt%DVB and 60 wt%n-heptane(with relative to the monomer)could endow the final PSILs with the relatively optimal catalytic performance.The preliminary experiment in the batch reactor indicated that PSILs herein exhibited higher catalytic activities than commercial Amberlyst 46 resin for the esterification of propanoic acid(PROAc)with n-propanol(PROOH).Consequently,the optimal PSILs catalyst,PVD-[Bim-SO3H]HSO4,was selected for further study in the batch reactive distillation column because of low cost and its ease of preparation.The yield of propyl ropionate(PROPRO)could reach up to 97.78%at the optimized conditions of PROOH/PROAc molar ratio(2:1)and catalyst dosage(2.0 wt%).The investigation of the reaction kinetic manifested that the calculated results of second order pseudo-homogeneous kinetic model were in good agreement with experimental values.The pre-exponential factor and activation energy were 4.12×107 L·mol-1·min-1 and 60.57 k J·mol-1,respectively.It is worth noting that the PSILs catalyst could be simply recovered and reused with relatively satisfactory decrease in the catalytic activity,which made it an environmental friendly and promising catalyst in the industrial application.

PREPARATION OF POLYMER MICROSPHERES WITH PYRIDYL GROUP AND THEIR STABILIZED GOLD METALLIC COLLOIDS

Narrow disperse poly（ethyleneglycol dimethacrylate-co-4-vinylpyridine） （poly（EGDMA-co-4-VPy）） microspheres were prepared by distillation-precipitation copolymerization of ethyleneglycol dimethacrylate （EGDMA） and 4-vinylpyridine （4-VPy） with 2,2＇-azobisisobutyronitrile （AIBN） as initiator in neat acetonitrile. The polymer microspheres containing pyridyl group were then utilized as stabilizer for gold metallic colloids with the diameter around 7 nm, which were prepared by the in situ reduction of gold chloride trihydrate with sodium borohydride through the coordination of the pyridyl group on the gel layer and surface of the microsphere with the gold metallic nano-particles. The catalytic properties of the pyridyl- functionalized microsphere-stabilized gold metallic colloids and the behavior of the stabilized-catalyst for the recycling were investigated with reduction of 4-nitrophenol to 4-aminophenol as a model reaction.

An efficient preparation of porous polymeric microspheres by solvent evaporation in foam phase

This paper reports an efficient method of preparing porous polymeric microspheres by solvent evaporation in foam phase,in which phase separation between polymer and porogen occurs in foam phase instead of that in water phase by using the traditional solvent eva poration method.The method provides outstanding features,including being time-saving,of high-yield and able for continuous production,in which formation of porous polymeric microspheres finished within 3 min with a high production yield up to approximate 95 wt% and the process was able to be developed into a continuous process for production of porous polymeric microspheres.It was also universal to non-crosslinked polymers since the method is a development on the traditional emulsion solvent evaporation method.The new method is efficient and can be used potentially on the industrial scale for continuous production of porous polymeric microsphere s.

Preparation and Characterization of Non-porous Superparamagnetic Microspheres with Epoxy Groups by Dispersion Polymerization

Non-porous superparamagnetic polymer microspheres with epoxy groups were prepared by dispersion polymerization of glycidyl methacrylate (GMA) in the presence of magnetic iron oxide (Fe3O4) nanoparticles coated with oleic acid. The polymerization was carried out in the ethanol/water medium using polyvinylpyrrolidone (PVP) and 2,2’-azobisisobutyronitrile (AIBN) as stabilizer and initiator, respectively. The magnetic microspheres obtained were characterized with scanning electron microscopy (SEM), vibrating sample magnetometry (VSM) and Fourier transform infrared spectroscopy (FTIR). The results showed that the magnetic microspheres had an average size of-1μm with superparamagnetic characteristics. The saturation magnetization was found to be 4.5emu.g-1. There was abundance of epoxy groups with density of 0.028 mmol·g^-1 in microspheres. The magnetic PGMA microspheres have extensive potential uses in magnetic bioseparation and biotechnology.

Fabrication of Microspheres Based on Poly(4-butyltriphenylamine) Blends with Poly(methyl methacrylate) and Block Copolymer by Solvent Evaporation Method

Micron-sized polymer particles from single poly(4-butyltriphenylamine) (PBTPA) homopolymer, binary polymer blend [PBTPA/poly(methyl methacrylate) (PMMA)], and ternary polymer blend (PBTPA/PBTPA-b-PMMA/PMMA) via a solvent evaporation method, and the surface morphologies and inside structure of resulting particles were investigated. Spherical homopolymer particles with smooth surface were resulted from PBTPA with low molecular weight. In the case of binary blends (PBTPA/PMMA = 1/1), Janus (low molecular weight) and dumbbell (high molecular weight) type morphologies were observed. The particles based on ternary blends containing PBTPA-b-PMMA showed core-shell type morphologies (PMMA;core, PBTPA;shell). Degree of engulfment of PMMArich domain increased with the content of the block copolymer. The decrease of domain size was not observed although the block copolymer had a suitable structure as a compatibilizer for the blend. It was also found that the initial concentration of polymer solution had an effect on the final morphology.

Characterization of Fe_3O_4/P(St-MPEO) Amphiphilic Magnetic Polymer Microspheres

Amphiphilic magnetic microspheres consisting of styrene and poly(ethylene oxide) macromonomer(MPEO) were prepared by dispersion copolymerization in the presence of Fe_3O_4 magnetic fluid in an ethanol/water medium. The sizes of the magnetic microspheres and their distribution were characterized by means of scanning electron microscopy(SEM). The surface morphology and the average surface roughness of the microspheres were investigated by virtue of atomic force microscopy(AFM). It was found that the microspheres exhibit microscopic phase-separate and the mean square surface roughness of the microspheres increases with increasing MPEO used in the copolymerization. The amphiphilic magnetic microspheres containing 0 4-3 5 mg/g hydroxyl groups could be prepared from MPEO with different concentrations and styrene.

Morphology Control of Polymer Microspheres Containing Block Copolymers with Seed Polymerization

Microspheres based on binary polymer blend consisting of polystyrene (PSt), poly (methyl methacrylate) (PMMA), block copolymer comprising PSt and PMMA subunits, and ternary polymer blend consisting of PSt, PMMA, and block copolymer were fabricated by a solvent evaporation method, in which a polymer solution in dichloromethane was dispersed in water phase with the aid of a homogenizer to obtain an O/W emulsion followed by solvent evaporation with agitation to solidify the polymer. In the case of ternary blend, the effect of block copolymer content on the morphology of resulting spheres was investigated. Ternary blends afforded the bi-compartmental morphologies, the intermediate morphology between Janus and core-shell, which was confirmed by TEM observation. Seed polymerization of St or MMA was also carried out utilizing the resulting microspheres as seed particles in order to control the shape, and the surface morphology of particles. The particles with snowman-like morphology were obtained by seed polymerization of St using PSt/PMMA binary blend microspheres as seed particles. Surface roughness was controlled by the polymerization of MMA in the block copolymer seed, and that of St in the ternary blend seed.

Local immunotherapy with interleukin - 2 delivered from biodegradable polymer microspheres combined with interstitial chemotherapy: a novel treatment for experimental malignant glioma.

OBJECTIVE:Local delivery of carmustine(BCNU)from biodegradablepolymers prolongs survival against experi-mental brain tumors.Moreover,paracrine administration of interleukin-2(IL-2)has been shown to elicit apotent antitumor immune response and to improve survival in animal brain tumor models.We report the use of anovel polymeric microsphere delivery vehicle to release IL-2.We demonstrate both in vitro release of cytokinefrom the microspheres and histological evidence of the inflammatory response elicited by IL-2 released from themicrospheres in the rat brain.Thees microspheres are used to deliver IL-2,and biodegradable polymer wafers

Ionic liquids functionalized β-cyclodextrin polymer for separation/analysis of magnolol

Ionic liquids functionalized β-cyclodextrin polymer, a mono-6-deoxy-6-（1,2-dimethylimida- zolium）-β-cyclodextrin iodide polymer （ILs-β-CDCP）, was synthesized as a solid-phase adsorbent coupled with high-performance liquid chromatography for separating or analyzing magnolol in drug samples. The results showed that magnolol was adsorbed rapidly on ILs-D-CDCP and eluted with methanol. Under the optimum conditions, preconcentration factor of the proposed method was 12. The linear range, limit of detection （LOD）, correlation coefficient （R） and relative standard deviation （RSD） were found to be 0.02-8.00 μg/mL, 1.9 ng/mL, 0.9992 and 2.76% （n=3, c=2.00 pg/mL）, respectively. The interaction between 1Ls-]）-CDCP and magnolol was studied through the inclusion constant, FTIR and TGA analysis. This proposed method has been successfully applied to the determination of magnolol in real samples.

Efficient recovery of aromatic compounds from the wastewater of styrene monomer and propylene oxide co-production plant via hypercrosslinked aryl-rich starch-β-cyclodextrin polymeric sorbent

Adsorptive recovery of valuable components from industrial wastewater is highly desirable for avoiding resource wastage but remains a challenge.Herein,we develop an efficient continuous adsorption process for recovering aromatic compounds in wastewater from styrene monomer and propylene oxide coproduction(SMPO)plant.Based on our insight into the potential of bio-based porous materials for adsorption application,starch-graft-polystyrene(SPS)and aryl-modifiedβ-cyclodextrin(ACD)were prepared,and novel hypercrosslinked porous polymers combined SPS with ACD(HSPS-ACDs)were synthesized through external crosslinking approach.In a binary-component system,the best-performing one HSPS-ACD(H)with high ACD content and large specific surface area possessed superior capacities for the representative aromatic compounds,acetophenone(AP,2.81 mmol·g^(-1))and 1-phenylethanol(1-PE,1.35 mmol·g^(-1))compared with the previously reported materials.Further,the adsorption properties of aromatic compounds on HSPS-ACD(H)were investigated in batch mode.For practical application,continuous adsorption experiments were conducted in a HSPS-ACD(H)-packed fixed bed,where the target aromatic components in wastewater were effectively retained and further released by elution.Besides showing the reversible adsorption and efficient enrichment effect,the HSPS-ACD(H)-packed fixed bed also maintained great stability in multiple cycles.Moreover,quantum chemical calculations were performed to elucidate the potential mechanism of adsorption of AP and 1-PE onto HSPS-ACD(H).

STUDIES ON THE POLYMERIZATION OF β-CYCLODEXTRIN WITH EPICHLOROHYDRIN

Different proportions of β-cydodextrin and epichlorohydrin were used to prepare a group of β-cyclodextrin polymers. The relationship between the reaction extent and the molar ratios of reactants was discussed according to the results of ~1H-NMR, ^(13) C-NMR spectra and elemental analysis. Especially, high resolution ~1H-NMR spectra were usd for studying the reaction active sites and the extent of reaction. The solubility of oil soluble drugs in water was largely improved in the presence of water-soluble β-cyclodextrin polymer.

Determination of Enantiomeric Purity of ν-Pyrrolidinyl Phenylpropanol by Capillary Electrophoresis Using β-Cyclodextrin Polymer as Chiral Selector

Enantiomer of (-pyrrolidinyl phenylpropanol was studied by capillary electrophoresis using (-cyclodextrin polymer as chiral selector. We determined the enantiomeric excess value of (-pyrrolidinyl phenylpropanol with RSD 0.48%.

Preparation of Dysprosium Ferrite/Polyacrylamide Magnetic Composite Microsphere and Its Characterization

Using the technique of microemulsion polymerization with nano-reactor, dysprosium ferrite/polyacrylamide magnetic composite microsphere was prepared by one-step method in a single inverse microemulsion. The structure, average particle size, morphology of composite microsphere were characterized by FTIR, XRD, TEM and TGA. The magnetic responsibility of composite microsphere was also investigated. The results indicate that the magnetic composite microsphere possess high magnetic responsibility and suspension stability.

Influence of Surfactant-polymer Complexes on Crystallization and Aggregation of CaCO_3

Hollow calcium carbonate（CaCO3） microspheres with different morphologies were synthesized via the precipitation reaction of calcium chloride with sodium carbonate in the presence of different surfactant-polymer complexes.The selected anionic surfactants were sodium dodecyl sulfonate（SDS） and sodium dodecyl benzenesulfonate（SDBS）,respectively.The selected water-soluble polymers were polyacrylic acid（PAA） and polyvinyl pyrrolidone（PVP）.In this work,SDS-PVP ＂pearl-necklace model＂ micellar complex was formed via hydrophobic effectiveness between SDS and PVP and it served as the spherical template to generate spherical CaCO3 aggregates with hollow microspheres composed of about 500 nm irregular shaped particles.SDS-PAA complexes and SDBS-PAA complexes formed ＂core-shell model＂ aggregates with calcium ions serving as the medium to link the anionic surfactant and the polymer.SDS-PAA ＂core-shell model＂ aggregates would act as templates for hollow CaCO3 microspheres consisting of 30―50nm irregular shaped crystallites.SDBS-PAA ＂core-shell model＂ aggregates served as the spherical aggregate templates to generate spherical CaCO3 aggregates consisted of many small spherical particles which had grown together.All the obtained CaCO3 hollow microspheres are calcite particles.This research may provide new insight into the control of morphologies of hollow CaCO3 microspheres in the presence of surfactantpolymer complexes.

Preparation of Conducting Poly N-methylaniline Microsphere and Its Antibacterial Performance to Sulfate Reducing Bacteria

Microspheres of conducting polymers poly N-methylaniline （PNMA） were successfully synthesized through oxidation of N-methylaniline without any template. The average diameter of the microspheres with a smooth surface was about 0.40 μm when 0.2 M N-methylanUine was oxidized with 0.2 M ammonium persulfate in 0.2 M of HClO4 solution. The size of microspheres can be controlled by changing reaction time and temperature. The acid concentration was critical for the formation of microspheres with smooth surfaces. The excellent antibacterial performance of PNMA in novolac epoxy coating to sulfate reducing bacteria was demonstrated. Moreover, in API media, PNMA inhibited growth of SRB and then reduced the corrosion rate of carbon steel remarkably.