Surface fabrication of hollow microspheres from N-methylated chitosan cross-linked with glutaraldehyde

We have successfully prepared biocompatible and biodegradable hollow microspheres with sizes between 2 and 5 mum using cyclohexane droplets as a template and the N-methylated chitosan (NMC) cross-linked with glutaraldehyde (GA) as the shell. The structure, morphology, and formation process of the hollow microspheres were characterized by FT-IR, (1)H and (13)C NMR, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results revealed that the microspheres exhibited a very smooth and hollow structure. This work confirmed that the hollow microspheres were accomplished by fabricating on the basis of chemical cross-linking on the surface of the emulsion droplets and by removing cyclohexane as core. The results from SEM and TEM indicated that the emulsion droplets covered with cross-linked NMC in the oil-in-water system aggregated together to form a precipitate of microspheres by coagulating with acetone. Moreover, the cross-linked NMC on the surface of the microspheres continuously cured to form the tight shell, whereas the inner area became a cavity with increase of the aging time, leading to the hollow microspheres. In addition, an anti-infective drug, ofloxacin (Floxin), encapsulated in the microspheres more rapidly released to reach 90 wt % at pH 7.4 within 8 h than at pH 1.2.     

One‐stage synthesis of narrowly dispersed polymeric core‐shell microspheres

A method of one‐stage soap‐free emulsion polymerization to synthesize narrowly dispersed core‐shell microspheres is proposed. Following this method, core‐shell microspheres of poly(styrene‐co‐4‐vinylpyridine), poly(styrene‐co‐methyl acrylic acid), and poly[styrene‐co‐2‐(acetoacetoxy)ethyl methacrylate‐co‐methyl acrylic acid] are synthesized by one‐stage soap‐free emulsion polymerization of a mixture of one or two hydrophobic monomers and a suitable hydrophilic monomer in water. The effect of the molar ratio of the hydrophobic monomer to the hydrophilic one on the size, the core thickness, and the shell thickness of the core‐shell microspheres is discussed. The molar ratio of the hydrophobic and hydrophilic monomers and the hydrophilicity of the resultant oligomers of the hydrophilic monomer are optimized to synthesize narrowly dispersed core‐shell microspheres. A possible mechanism of one‐stage soap‐free emulsion polymerization to synthesize core‐shell microspheres is suggested and coagglutination of the oligomers of the hydrophilic monomers on the hydrophobic core is considered to be the key to form core‐shell microspheres. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1192–1202, 2008     

Yolk‐Shell Porous Microspheres of Calcium Phosphate Prepared by Using Calcium L‐Lactate and Adenosine 5′‐Triphosphate Disodium Salt: Application in Protein/Drug Delivery

A facile and environmentally friendly approach has been developed to prepare yolk‐shell porous microspheres of calcium phosphate by using calcium L ‐lactate pentahydrate (CL) as the calcium source and adenosine 5′‐triphosphate disodium salt (ATP) as the phosphate source through the microwave‐assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk‐shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk‐shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as‐prepared yolk‐shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH‐responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk‐shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery.     

Chromatographic studies of mitomycin C degradation in albumin microspheres

Serum albumins and polylactic acid (PLA) have been used as bioerodable polymers in the preparation of drug-containing microspheres for parenteral drug delivery. The albumin microsphere may be prepared via either chemical cross-linking or heat denaturation of the protein. Heat-denatured albumin microspheres containing mitomycin C (MMC) have been used in pre-clinical and clinical investigations. Due to the high reactivity of MMC as a bifunctional alkylating agent, a study on the stability of MMC in the albumin and PLA microspheres has been carried out using a high-performance liquid chromatographic (HPLC) method. Human serum albumin (HSA) microspheres were prepared using an emulsion method via either heat denaturation at 120 or 170 degrees C or the use of 0.5 M biacetyl as a cross-linking agent. The PLA microspheres were prepared by an emulsion method at 55 degrees C. HPLC analysis of the HSA microspheres showed that about 37% of MMC was converted to 2,7-diaminomitosene derivatives in microspheres prepared by heat denaturation at 120 degrees C. The degradation increased to 82% when the microspheres were prepared with a denaturation temperature of 170 degrees C. The use of biacetyl as a cross-linking agent in the preparation of HSA microspheres resulted in a complete degradation of the incorporated MMC. Biacetyl was found to interact with MMC leading to the formation of 7-aminomitosene derivatives. In contrast to the albumin system, MMC may be incorporated into PLA microspheres without degradation.     

Simple coacervates of zein to encapsulate Gitoxin

This work reports the use of simple coacervates of the hydrophobic protein zein to encapsulate Gitoxin, a cardiotonic glycoside. The microspheres obtained using ethanol, methanol, iso-propyl alcohol were characterized using viscosity index, scanning electron microscopy (SEM) and laser light scattering particle analyzer. Scanning electron micrographs indicated that the zein film was made of microspheres with diameter in the 1-1.5 microm range, which could be controlled. Sizes of Gitoxin-loaded zein microspheres changed little before and after release of the drug because of conglutination among zein microspheres. Release of Gitoxin from zein microspheres, were performed in vitro to investigate the mechanism of model drug release. The results show that the zein microspheres obtained using ethanol are best suited for use as a sustained-release form of Gitoxin. The microspheres may also be useful in drug targeting system since the diameter of the microspheres is appropriate for phagocytosis by macrophages. Both zein film and Gitoxin-loaded zein microsphere film were effective in suppressing platelet adhesion.     

Reversible addition‐fragmentation chain transfer polymerization of a typical hydrophobic monomer of styrene within microreactor of shell‐corona hollow microspheres suspending in water

Reversible addition‐fragmentation chain transfer (RAFT) polymerization of a typical hydrophobic monomer of styrene within microreactor of shell‐corona hollow microspheres of poly(styrene‐co‐methacrylic acid) suspending in water is studied. The shell‐corona hollow microspheres contain a hydrophilic corona of poly(methacrylic acid) (PMAA) and a cross‐linked polystyrene shell, which can suspend in water because of the hydrophilic corona of PMAA. The size of the shell‐corona hollow microspheres is about 289 nm and the extent of the microcavity of the hollow microsphere is 154 nm. These shell‐corona hollow microspheres can act as microreactor, within which the typical hydrophobic monomer of styrene, the RAFT agent of S‐benzyl dithiobenzoate and the initiator of 2,2′‐azobisisobutyronitrile can be encapsulated and RAFT polymerization of styrene takes place in well controlled manner in water. It is found that the resultant polymer of polystyrene has a competitively low polydispersity index and its number‐average molecular weight linearly increases with monomer conversion. The method is believed to be a new strategy of RAFT polymerization of hydrophobic monomer in aqueous solution. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Effect of Hydrophilic Shells on the Formation of Colloidal Crystals by Monodisperse Core‐Shell Polymer Microspheres

We have found that a soft, hydrophilic shell is necessary in the formation of three‐dimensional colloidal crystals by polymeric microspheres prepared by surfactant‐free emulsion copolymerization. The core‐shell microspheres contain a hard, hydrophobic polystyrene core and a soft, hydrophilic shell made of polyacrylamide or poly(acrylic acid) (PAA). Dilution of the particles induced a red shift of the diffraction peak. We have found a pH switching effect for the formation of colloidal crystals by the microspheres with a PAA shell. When the carboxylic‐acid groups are protonated, the colloidal crystals lose their order. The same effect is observed when a poor solvent is added to the colloidal crystals formed by the microspheres with a polyacrylamide shell.

     

Size and charge characterization of polymeric drug delivery systems by Taylor dispersion analysis and capillary electrophoresis

In this work, Taylor dispersion analysis and capillary electrophoresis were used to characterize the size and charge of polymeric drug delivery nanogels based on polyglutamate chains grafted with hydrophobic groups of vitamin E. The hydrophobic vitamin E groups self-associate in water to form small hydrophobic nanodomains that can incorporate small drugs or therapeutic proteins. Taylor dispersion analysis is well suited to determine the weight average hydrodynamic radius of nanomaterials and to get information on the size polydispersity of polymeric samples. The effective charge was determined either from electrophoretic mobility and hydrodynamic radius using electrophoretic modeling (three different approaches were compared), or by indirect UV detection in capillary electrophoresis. The influence of vitamin E hydrophobicity on the polymer effective charge has been studied. The presence of vitamin E leads to a drastic decrease in polymer effective charge in comparison to non-modified polyglutamate. Finally, the electrophoretic behavior of polyglutamate backbone grafted with hydrophobic vitamin E (pGVE) nanogels according to the ionic strength was investigated using the recently proposed slope plot approach. It was deduced that the pGVE nanogels behave electrophoretically as polyelectrolytes which is in good agreement with the high water content of the nanogels.

具有核壳结构磁性复合微球的制备与表征

采用两步法制备了具有核壳结构的Fe3O4/P(MMA/DVB)(core)-P(St/GMA/DVB)(shell)磁性复合微球.首先,用改进的细乳液聚合制备了Fe3O4/P(MMA/DVB)微球;然后,加入总量不同的苯乙烯(St)、甲基丙烯酸缩水甘油酯(GMA)和二乙烯基苯(DVB),通过种子乳液聚合,制备了不同磁含量的核壳结构的磁性复合微球.分别用X-射线衍射(XRD)、高倍透射电镜(HR-TEM)、热重分析(TGA)、振动样品磁力计(VSM)等手段对磁性微球的性能进行了表征.实验结果表明,Fe3O4/P(MMA/DVB)微球的磁含量为84 wt%;通过改变加入壳层单体的量,核壳复合微球的磁含量可控在20 wt%~76 wt%之间.该微球具有超顺磁性,相应的饱和磁化强度为12~50Am2/kg.     

ZrO2中空微球的模板法制备及吸附性能研究

以油菜花粉为生物模板,通过温和易控的水浴-陈化法制备了纳/微米结构ZrO2中空微球.利用扫描电子显微镜(SEM)、红外光谱(FTIR)、X射线能谱(EDS)、X射线衍射(XRD)、比表面孔隙度分析、热分析等对所制备的产物和前驱体进行了表征,并对产物的吸附性能进行了初步的研究.结果表明,ZrO2中空微球的球壳由纳米粒子构筑并形成介孔结构.花粉模板前处理方式不同,其模板作用不同,可以获得两种不同球壳厚度、表面形貌和比表面积的ZrO2中空微球.其中"镂空"结构的ZrO2微球对铬黑T有良好的吸附性能.对ZrO2中空结构形成的机理进行了分析和讨论.     

Fabrication of polymeric-Laponite composite hollow microspheres via LBL assembly

Hollow structure microspheres with composite polymeric-Laponite shells were prepared by electrostatic self-assembly of Laponite on the polymeric hollow microspheres in this work. The multilayer hydrophilic core/hydrophobic shell polymer latex particles containing carboxyl groups inside were first synthesized via seeded emulsion polymerization, followed by alkali treatment, generating polymeric hollow microspheres. Then, polyethyleneimine (PEI) and Laponite were alternately electrostatic adsorbed on the prepared polymeric hollow microspheres to form polymeric-Laponite composite hollow microspheres. It was indicated that the morphology of alkali-treated microspheres could be tuned through simply altering the dosage of alkali used in the post-treatment process. Along with the increasing of the coating layers, the zeta potential of microspheres absorbed PEI or Laponite approximately tended to be constant respectively, and the thickness of Laponite layer around the hollow microspheres increased clearly, getting more uniform and homogenous. Furthermore, the corresponding polymeric-Laponite hollow microspheres showed high pressure resistance ability compared to the polymeric hollow microspheres.     

Preparation and surface modification of magnetic poly(methyl methacrylate) microspheres

~~Preparation and surface modification of magnetic poly(methyl methacrylate) microspheres~~     

Synthesis of a paraffin phase change material microencapsulated in a siloxane polymer

The coemulsification method suitable for the formulation of microcapsules of n-eicosane coated with a polysiloxane is developed. This method allows to synthesize core–shell microcapsules of paraffin which have the shape of spheres or distorted spheres and are designed for the use as phase change materials. The microcapsules are formed in aqueous phase by the precipitation of n-eicosane together with modified polyhydromethylsiloxane from a common solvent which is miscible with aqueous media. The polysiloxane is modified by the attachment of silylvinyl and alkoxy functions before coemulsification with the paraffin. It also contains the Pt(0) Karstedt catalyst. The microcapsules formed by coemulsification are stabilized by the in situ cross-linking of the polysiloxane shell. The shell is additionally modified by the in situ generation of silanol groups which provide colloidal stabilization of microspheres in aqueous phase. Microcapsules were studied by DSC, SEM, optical polarized microscope, and by thermooptical analysis (TOA).     

A new simple method to prepare hollow PES microspheres

A new simple method for the formation of hollow polyethersulfone (PES) microspheres was reported in this paper. Coaxial electrospraying equipment and nonsolvent precipitating bath were used to produce hollow microspheres in one step. The properties of the core solution affected the formation of hollow PES microspheres. To form hollow microspheres in one step, the core solution should be removed directly by a nonsolvent. Additionally, the core solution should also be used to occupy the internal space of microspheres and form a supporting layer at the interface between the core solution and the shell solution. The supporting layer formed by the micro-phase that was caused by the phase separation of the core or shell solution was the key factor for the formation of hollow PES microspheres. The performance of hollow microspheres produced by this method was excellent. This method provided a new simple way to form hollow polymer microspheres and can be extended to other polymers to prepare hollow microspheres in one step.     

PAm-g-PMAA亲水性聚合物微球的合成

利用链转移自由基聚合和端基置换反应法 ,合成了苯乙烯基单封端的聚甲基丙烯酸叔丁酯 (PBMA)大分子单体 .在N ,N′ 亚甲基二丙烯酰胺 (Bis A)存在的条件下 ,使PBMA大分子单体与亲水性单体丙烯酰胺(Am)在乙醇 水的混合介质中进行分散共聚反应 ,得到了表面为PBMA接枝的聚丙烯酰胺 (PAm g PBMA)聚合物微球 .将所得PAm g PBMA微球在酸性条件下水解 ,得到了整体亲水的聚甲基丙烯酸接枝的聚丙烯酰胺(PAm g PMAA)聚合物微球 .用激光光散射、透射电子显微镜和X射线光电子能谱仪等对聚合物微球的直径、形态及表面组成进行了表征 .研究结果表明 ,在共聚反应中PBMA大分子单体的分子量与浓度、Bis A浓度和介质的组成对微球的形成与颗粒直径的大小有明显影响 ;所形成的聚合物颗粒是以PBMA为壳、以交联PAm为核的核壳结构微球 .     

Self-assembled microspheres from f-block elements and nucleoamphiphiles

Hollow microspheres featuring a hybrid lipid-cation multilamellar shell are prepared by hydration of a nucleoside based amphiphile with an aqueous solution containing either actinide or lanthanide salts. The physico-chemical data collected clearly indicate that the formation of these microspheres is a consequence of the following concomitant stabilizing factors: (i) hydrophobic interactions, (ii) nucleobase dimer formation and (iii) phosphate/f-block element salt binding.     

Cross-linking-induced permanently perpendicular helix orientation in surface-grafted polyglutamate films

Using a chemical cross-linking procedure, surface-grafted polyglutamate films with a permanently perpendicular helix orientation were prepared. A surface-grafted alpha-helical polyglutamate film containing polymerizable side groups was synthesized by ring-opening terpolymerization of 50 molar% gamma-methyl-L-glutamate N-carboxyanhydride (NCA), 30% gamma-stearyl-L-glutamate NCA and 20% gamma-4-vinylbenzyl-L-glutamate NCA initiated from a silicon substrate functionalized with primary amino groups. The average tilt angle of the end-grafted helices in this film is approximately 66 degrees , indicating a nearly parallel helix orientation with respect to the substrate surface. After swelling of the grafted terpolyglutamate film in stearyl methacrylate and subsequent radical cross-linking, the average helix tilt angle decreases to about 11 degrees, indicating an almost perpendicular helix orientation. The film thickness increases accordingly from 151 A before to approximately 390 A after cross-linking. Extensive solvent treatment of the cross-linked film shows that the perpendicular helix orientation is permanent.     

Formation of zein spheres by evaporation-induced self-assembly

Zein is an amphiphilic protein capable of self-assembly into microspheres. Zein microspheres may form by evaporation-induced self-assembly (EISA) of zein solutions in ethanol/water. The formation of microspheres is of particular interest for the development of delivery systems. Zein solutions in ethanol/water 75?% (v/v) were slowly evaporated to promote self-assembly of microspheres. The ethanol content of the solvent decreased during EISA changing solvent polarity which induced self-assembly of zein particles. The growth of zein spheres was modeled from the hydrophobic and hydrophilic contributions to the interfacial free energy (R ²?=?0.92). The good fit indicated that during EISA zein microspheres increased in size due to hydrophobic interactions between zein molecules. The model may allow the prediction of evaporation time and thus control over microsphere size.     

Study on the morphological regulation mechanism of hollow silica microsphere prepared via emulsion droplet template

The morphology regulation of hollow silica microspheres is significant for their properties and applications. In this paper, hollow silica microspheres were formed through the hydrolysis and condensation reaction of tetraethyl orthosilicate (TEOS) at the interface of the emulsion droplet templates composed of liquid paraffin and TEOS, followed by dissolving paraffin with ethanol. The effects of various factors including the emulsifier structure and content, TEOS content, catalyst type, and the ethanol content in the continuous water phase on the particle size, shell thickness and morphology of the prepared hollow silica microspheres were studied in detail. The results show that the diffusion and contact of TEOS and water molecules as well as the hydrolysis condensation reaction of TEOS at the oil-water interface are two critical processes for the synthesis and morphological regulation of hollow silica microspheres. Cationic emulsifier with a hydrophobic chain of appropriate length is the prerequisite for the successful synthesis of hollow silica microspheres. The ethanol content in water phase is the dominant factor to determine the average diameter of hollow microspheres, which can vary from 96 nm to 660 nm with the increase of the volume ratio of alcohol-water from 0 to 0.7. The silica wall thickness varies with the content and the hydrophobic chain length of the emulsifier, TEOS content, and the activity of the catalyst. The component of the soft template will affect the morphology of the silica wall. When the liquid paraffin is replaced by cyclohexane, hollow microspheres with fibrous mesoporous silica wall are fabricated. This work not only enriches the basic theory of interfacial polymerization in the emulsion system, but also provides ideas and methods for expanding the morphology and application of hollow silica microspheres.     

Encapsulation and release of aqueous components from sonochemically produced protein microspheres

Aqueous solutions of salts or dyes have been contained in sonochemically produced lysozyme microspheres by encapsulating an inverse emulsion in tetradecane. Release can be triggered by chemically disrupting crosslinking in the protein shell or by mechanical disruption using high intensity ultrasound.