Effects of reaction temperature and reaction time on positive thermosensitivity of microspheres with poly(acrylamide)/poly(acrylic acid) IPN shells

We have successfully prepared monodispersed positively thermoresponsive core-shell hydrogel microspheres with poly(acrylamide-co-styrene) [P(AAM-co-St)] cores and IPN(interpenetrating polymer network)-based shells composed of poly(acrylamide)/poly(acrylic acid). The submicron-sized monodispersed P(AAM-co-St) core seeds were prepared by using a surfactant-free emulsion polymerization method, and the IPN-based shell layers were fabricated onto the core seeds by using a method of sequential IPN synthesis. Effects of reaction time and reaction temperature during preparation of IPN on the particle size, monodispersity, and thermoresponsive characteristics of microspheres were investigated. The results show that the sizes of particles with IPN shell layer are smaller than that of seeds, and the change of monodispersity among them is not obvious and the monodispersity of particles prepared under higher reaction temperature is higher than that of seeds and those particles prepared under lower reaction temperature. With increasing reaction time, thermoresponsive characteristics of microspheres increases. While thermoresponsive characteristics of microspheres decreases sharply with increasing reaction temperature. The results display preparation of IPN-structured microspheres is so careful to need longer reaction time and lower reaction temperature.     

Study of SPG membrane emulsification processes for the preparation of monodisperse core-shell microcapsules

Experimental investigations on the Shirasu-porous-glass (SPG)-membrane emulsification processes for preparing monodisperse core-shell microcapsules with porous membranes were carried out systematically. The results showed that, to get monodisperse oil-in-water (O/W) emulsions by SPG membrane emulsification, it was more important to choose an anionic surfactant than to consider hydrophile-lipophile balance (HLB) matching. Increasing the viscosity of either the disperse phase or the continuous phase or decreasing the solubility of the disperse phase in the continuous phase could improve both the monodispersity and the stability of emulsions. With increasing monomer concentration inside the disperse phase, the monodispersity of emulsions became slightly worse and the mean diameter of emulsions gradually became smaller. Monodisperse monomer-containing emulsions were obtained when the SPG membrane pore size was larger than 1.0 micro m, and from these emulsions satisfactory monodisperse core-shell microcapsules with a porous membrane were prepared. On the other hand, when the SPG membrane pore size was smaller than 1.0 mciro m, no monodisperse emulsions were obtained because of the formation and chokage of solid monomer crystals in the pores or at the end of the pores of the SPG membrane. This was due to the remarkable solvation and diffusion of the solvent in water. With increasing the emulsification time the average emulsion diameter generally decreased, and the monodispersity of the emulsions gradually became worse.     

Adsorption of poly(N-isopropylacrylamide-co-4-vinylpyridine) onto core-shell poly(styrene-co-methylacrylic acid) microspheres

Adsorption of the thermoresponsive copolymer of poly(N-isopropylacrylamide-co-4-vinylpyridine) (PNIPAM-co-P4VP) onto the core-shell microspheres of poly(styrene-co-methylacrylic acid) (PS-co-PMAA) is studied. The core-shell PS-co-PMAA microspheres are synthesized by one-stage soap-free polymerization in water. The copolymer of PNIPAM-co-P4VP is synthesized by free radical polymerization of N-isopropylacrylamide and 4-vinylpyridine in the mixture of DMF and water using K₂S₂O₈ as initiator. Adsorption of PNIPAM-co-P4VP onto the core-shell PS-co-PMAA microspheres results in formation of the composite microspheres of PS/PMAA-P4VP/PNIPAM. The driven force to adsorb the copolymer of P4VP-co-PNIPAM onto the core-shell PS-co-PMAA microspheres is ascribed to hydrogen-bonding and electrostatic affinity between the P4VP and PMAA segments. The resultant composite microspheres of PS/PMAA-P4VP/PNIPAM with surface chains of PNIPAM are thermoresponsive in water and show a cloud-point temperature at about 33 °C.     

Preparation of thermoresponsive core–shell polymeric microspheres and hollow PNIPAM microgels

A reliable and efficient route for preparing thermoresponsive hollow microgels based on cross-linked poly(N-isopropyl acrylamide) (PNIPAM) was developed. Firstly, monodisperse thermoresponsive core–shell microspheres composed of a P(styrene (St)-co-NIPAM) core and a cross-linked PNIPAM shell were prepared by seeded emulsion polymerization using P(St-co-NIPAM) particles as seeds. The size of the P(St-co-NIPAM) core can be conveniently tuned by different dosages of sodium dodecyl sulfate. The thickness of the cross-linked PNIPAM shell can be controlled by varying the dosage of NIPAM in the preparation of PNIAPM shell. Then, hollow PNIPAM microgels were obtained by simply dissolving the P(St-co-NIPAM) core with tetrahydrofuran. The core–shell microspheres and the hollow microgels were characterized by transmission electron microscopy, dynamic light scattering, atomic force microscopy, and Fourier-transform infrared spectroscopy.     

原位聚合法制备具有温敏PNIPAM壳的核-壳结构聚合物纳米微球的研究

结合大分子自组装和原位自由基聚合方法,采用油溶性引发剂偶氮二异丁腈(AIBN),在聚(ε-已内酯)(PCL)纳米粒子表面引发聚合单体N-异丙基丙烯酰胺(NIPAM)和交联剂亚甲基双(丙烯酰胺)(MBA),制备得到了核-壳结构的PCL/PNIPAM聚合物纳米微球.系统研究了单体和交联剂用量、壳层目标交联度、初始PCL/DMF溶液的浓度及引发剂AIBN含量4个反应参数对核-壳结构PCL/PNIPAM纳米微球的PNIPAM壳层得率、微球尺寸、温敏性能及电镜形貌的影响.结果表明,在制备核-壳结构PCL/PNIPAM纳米微球的反应过程中,PCL粒子表面的聚合和水中的聚合二者之间相互竞争.适当增加引发剂AIBN的添加量,有利于制备得到核/壳比例可控的PCL/PNIPAM纳米微球;交联剂MBA较高的反应活性导致形成了非均匀交联的PNIPAM壳层.     

Correlative studies on the fabrication of poly(styrene-methyl-methacrylate-acrylic acid) colloidal crystal films

This research describes a one-step procedure for monodispersed poly(styrene-methyl-methacrylate-acrylic acid colloidal spheres [P(St-MMA-AA)] via soap-seeded emulsion polymerization. The effects ofreaction conditions such as temperature, stirring speed, initiation concentration, e.t.c. were examined. The results obtained showed that the spheres average particle diameter decreased with increase in initiator concentration, the reaction temperature and stirring speed and increased with an increase in monomer concentrations. The particles show stable mechanical properties within the transition and heating temperatures of 111.9?°C and 388?°C respectively. Zeta-potential values ranging from ?31.8?mV to ?36.5?mV which is indicative of stable dispersion of colloidal particles were obtained for all the prepared latexes. The assembled colloidal latex had periodic structures with mainly hexagonal three-dimensional structures with multi-facet arrangements. The latex also shows spherical shape of monodispersed core-shell particles.     

Preparation of Monodisperse Cationic Microspheres by Dispersion Polymerization of Styrene and a Cation-Charged Monomer in the Absence of a Stabilizer

Cationic polystyrene (PS) microspheres with monodispersity were prepared by dispersion polymerization of styrene and [2-(methacyrloyloxy) ethyl] trimethylammonium chloride (METMAC) in methanol/water system. The effects of METMAC, styrene, and initiator concentration as well as solvent composition on the diameters and size distribution of PS microspheres were systematically investigated. The results indicated that monodisperse cationic PS microspheres could be generated at METMAC concentration less than 2 mol% relative to styrene amount, and too high or low styrene amount was unfavorable to produce cationic PS microspheres. Moreover, it was found that with initiator concentration increasing, the average diameter and the size distribution of cationic PS microspheres also markedly increased. Solvent composition played a significantly important role in the preparation of cationic PS microspheres by dispersion polymerization of styrene and METMAC. Finally, the possible growth and stabilization mechanism of cationic PS microspheres was proposed. The electrostatic repulsion derived from positive charge on the surface of PS microspheres was responsible for the stabilization during dispersion polymerization in the absence of a stabilizer.     

明胶微球粒径控制的研究

采用乳化-凝聚法,在油包水(w/o)的体系中对明胶微球(GMs)粒径、微球的形态和分散性等进行了研究.扫描电子显微镜(SEM)和粒径分布曲线的结果表明在乳化体系中,提高明胶溶液的浓度或水油比例,明胶微球的粒径增大;增加乳化剂的用量,微球的粒径减小;选择合适的乳化时间和搅拌速率,可以改善微球的分散性和表面光滑程度.同时,通过调控实验条件,在明胶溶液浓度0.100 g/mL,水油比1/5,乳化剂浓度0.05g/mL时研制出了平均粒径为3.58μm的表面光滑、分散性好的明胶微球.     

具有广谱紫外屏蔽性能的三元共聚物微球的制备

以醋酸乙烯酯(VA)、 马来酸酐(MA)和商品化的紫外吸收剂2-{2-羟基-5-[2-(甲基丙烯酰氧)乙基]苯基}-2H-苯并三唑(NB)为单体, 偶氮二异丁腈(AIBN)为引发剂, 通过自稳定沉淀聚合法(2SP)制备了具有广谱紫外屏蔽性能的单分散三元共聚物微球(PVMN); 研究了溶剂、 单体配比、 引发剂用量、 单体浓度、 反应温度和反应时间对共聚物微球形态和性能的影响. 研究结果表明, 体积比为7∶3的苯甲酸乙酯/正庚烷混合溶剂是2SP法合成单分散PVMN微球的理想溶剂. 随着单体配比中紫外吸收单体NB比例的增加, 引发剂用量、 单体浓度、 反应温度的提高和反应时间的延长, 微球的粒径随之增大, 进而改变了微球的紫外屏蔽性能. 本文制备的微球的粒径范围为(249±19)~(1434±213) nm, 优化得到的PVMN微球可屏蔽约90%的紫外光. 该策略还可扩展到其它可用作紫外吸收剂的乙烯基单体, 是一种制备稳定高分子紫外屏蔽剂的通用方法.     

P(St-AM)核壳聚合物微球的制备及其光子晶体膜

采用一步乳液聚合法,调节引发剂用量,制备了不同粒径的具有核壳结构的功能性聚(苯乙烯-丙烯酰胺)乳胶微球.用透射电子显微镜表征了乳胶微球的核壳结构和粒径,所制微球的粒径分别为195,217,234和255 nm.用红外光谱对微球的化学成分进行了表征,证实聚丙烯酰胺已包覆在聚苯乙烯外层.通过竖直沉积自组装法制备了聚合物微球的光子晶体薄膜.扫描电子显微镜表征了所制光子晶体膜的表面形貌,反射和透射光谱表征了光子禁带.结果表明,聚合物微球以面心立方紧密堆积,其(111)面与基底平行;微球粒径不同,光子晶体的光子禁带不同.制备了不同光子禁带的光子晶体,禁带分别位于473,515,574和630 nm,相应的薄膜分别呈蓝色、绿色、黄色和红色,对于光子晶体的拓展和应用具有重要的意义.     

交联剂加入方式对聚苯乙烯微球形貌和分散性能的影响

以醇水混合液为分散介质,偶氮二异丁腈为引发剂,聚乙烯吡咯烷酮为稳定剂,二乙烯基苯为交联剂,采用分散聚合法一步制备了粒径约为1μm的单分散交联聚苯乙烯微球;采用扫描电镜和激光粒度仪等分析微球表面形貌及粒径分布,研究了滴加交联剂开始时间、交联剂浓度、引发剂浓度等对微球形貌和分散性能的影响.结果表明,在实验进行4h时加入交联剂,且交联剂滴加持续时间为2h的条件下,可制得平均粒径为1μm左右的交联聚苯乙烯微球,其具有较好的单分散性和球形度,且表面光滑.     

The influence of chitosan on in vitro properties of Eudragit RS microspheres

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.     

聚二乙烯基苯微球的合成及其表征研究

采用分散聚合方法制备了聚二乙烯基苯微球 ,研究了引发剂、稳定剂、单体 溶剂比例和溶剂种类对微球粒径及其分布的影响 ,在适当的条件下可以得到平均粒径较大、粒径分布较窄的微球 .用红外光谱法研究了聚合物微球内稳定剂、悬挂双键以及对位和间位二乙烯基苯含量随聚合过程的进行发生的变化 .测得的微球TG曲线表明 ,聚合物微球具有良好的热稳定性 .     

Thermoresponsive submicron-sized core–shell hydrogel particles with encapsulated olive oil

Thermoresponsive submicron-sized core–shell hydrogel particles with incorporated olive oil were synthesised and studied. The microspheres having poly(N-isopropylacrylamide-co-methyl methacrylate) core and poly(N-isopropylacrylamide) shell were synthesised by emulsifier-free seed polymerisation method. The morphology, particle size and distribution characteristics of the core microspheres were studied with different amount of initiator, monomer–solvent ratio and polymerisation time using scanning electron microscopy and dynamic light scattering particle size analysis. The prepared core and core–shell microspheres were regularly spherical with average size of around 190.0 and 320.0 nm respectively and nearly monodispersed size distribution. Transmission electron microscopy study revealed the core–shell structure of the microspheres. The thermoresponsive transition temperature (T _t) of the core–shell microspheres was determined as 33 °C by optical absorbance measurement, dynamic light scattering particle size analysis and differential scanning calorimetry. The release rate of olive oil from core–shell microspheres was accelerated by squeezing out the entrapped olive oil as the temperature was increased above T _t. Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy study indicated the formation of copolymer.     

Studies on the particle size control of gelatin microspheres

A series of gelatin microspheres (GMs) were prepared through emulsification-coacervation method in water-in-oil (w/o) emulsions. The influence of preparation parameters on particle size, surface morphology, and dispersion of GMs was examined. The studied preparation parameters include concentration of gelatin solutions, concentration of the emulsifier, w/o ratio, emulsifying time, stirring speed, and so on. The surface morphology, dispersion, and particle sizes of GMs were determined by the scanning electron microscopy (SEM), SemAfore 4 Demo software, and particle size distribution graphic charts. The experimental results indicated that increasing the concentration of gelatin solution would increase the particle size of GMs. When the solution concentration increased from 0.050 to 0.200 g/mL gradually, the particle size increased correspondingly. The relationship between the two quantities was linear. On the contrary, increasing the concentration of the emulsifier would decrease the particle size of GMs. Furthermore, the particle size reduced quickly at initial time and slowed down latterly. With the increase of emulsifier concentration from 0 to 0.020 g/mL, themean diameters ofGMsdecreased from 17.32 to 5.38 μm. However, the particle size dwindled slowly when emulsifier concentration was higher than 0.020 g/mL. The excellent result was obtained with the condition of 0.050 g/mL of emulsifier concentration, 0.100 g/mL of gelatin solution concentration, 1/5 of w/o ratio, 10 min of emulsifying time, and 900 r/min of the stirring speed. The GMs prepared at this condition had the smallest sizes, the narrowest size distribution, the best spherical shape, and fluidity. The w/o ratio has the same influence on particle size of GMs as that of gelatin solution concentration. With the increase of w/o ratio, the average particle sizes increased linearly, and the surface of microspheres become smoother as well. It is supposed that w/o ratio can be used to change the diameters and surface morphologies of GMs. The emulsifying time has little influence on the mean diameters of GMs, but it affects the dispersion of GMs apparently. When the emulsifying time was shorter than 5 min, the GMs had bad dispersion. After increasing the emulsifying time to 13 min, the dispersion of GMs changed greatly, whereas the dispersion of GMs became bad again when the emulsifying time was longer than 13 min. According to the experimental results, 13 min was considered to be the best emulsifying time. The stirring speed has the similar influence on GMs’ morphologies as that of emulsifying time. Slow stirring rate made large size distribution and bad spherical shape of GMs; excessive stirring speed results in aggregation among GMs likewise. The smaller size distribution and better spherical shape of GMs were observed under the stirring rate between 500 and 1500 r/min by SEM. In conclusion, increasing the concentration of gelatin solution or w/o ratio would increase the particle sizes of GMs, increasing the concentration of the emulsifier would decrease the sizes of GMs at proper emulsifying time, and stirring speed would get the best spherical shape of GMs. These are the basic laws governing the design and manufacture of the GMs. __________ Translated from Acta Polymerica Sinica, 2008, 8 (in Chinese)     

Preparation of monodispersed polystyrene microspheres uniformly coated by magnetite via heterogeneous polymerization

Composite microspheres of core-shell type were prepared by a seeded polymerization using monodispersed polystyrene seed latex (Ps) combined with an in situ dispersion of magnetite (Fe₃O₄) fine particles. The heterogeneous polymerization was carried out in aqueous dispersions of the Fe₃O₄ particles modified with sodium oleate. All the synthetic processes were carried out in a wet state to avoid serious agglomeration. The morphology of the composite particle and the size distribution were examined to discuss the effects on the polymerization parameters, such as monomer concentration, type and concentration of an initiator, magnetite particle concentration and the method of surface modification of Fe₃O₄.     

pH-Responsive hollow polymeric microspheres and concentric hollow silica microspheres from silica-polymer core-shell microspheres

Nearly monodispersed silica-poly(methacrylic acid) (SiO 2-PMAA) core-shell microspheres were synthesized by distillation-precipitation polymerization from 3-(trimethoxysilyl)propylmethacrylate-silica (SiO 2-MPS) particle templates. SiO 2-PMAA-SiO 2 trilayer hybrid microspheres were subsequently prepared by coating of an outer layer of SiO 2 on the SiO 2-PMAA core-shell microspheres in a sol-gel process. pH-Responsive PMAA hollow microspheres with flexible (deformable) shells were obtained after selective removal of the inorganic SiO 2 core from the SiO 2-PMAA core-shell microspheres by HF etching. The pH-responsive properties of the PMAA hollow microspheres were investigated by dynamic laser scattering (DLS). On the other hand, concentric and rigid hollow silica microspheres were prepared by selective removal of the PMAA interlayer from the SiO 2-PMAA-SiO 2 trilayer hybrid microspheres during calcination. The hybrid composite microspheres, pH-sensitive hollow microspheres, and concentric hollow silica microspheres were characterized by field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray (EDX) analysis.     

Surface plasmon spectroscopy of gold-poly-N-isopropylacrylamide core-shell particles

Highly uniform, core-shell microgels consisting of single gold nanoparticle cores and cross-linked poly-N-isopropylacrylamide (PNIPAM) shells were prepared by a novel, versatile protocol. The synthetic pathway allows control over the polymer shell thickness and its swelling behavior. The core-shell structure was investigated by electron microscopy and atomic force microscopy, whereas the swelling behavior of the shell was studied by means of dynamic light scattering and UV-vis spectroscopy. Furthermore, the latter method was used to investigate the optical properties of the hybrid particles. By modeling the scattering contribution from the PNIPAM shells, the absorption spectra of the gold nanoparticle cores could be recovered. This allows the particle concentration to be determined, and this in turn permits the calculation of the molar mass of the hybrid particles as well as the refractive index of the shells.     

蒸馏沉淀聚合法制备窄分散聚二乙烯基苯-co-丙烯腈功能聚合物微球

采用蒸馏沉淀聚合法,利用过氧化苯甲酰(BPO)为引发剂,在不加任何稳定剂和不搅拌的情况下,丙烯腈(AN)和二乙烯基苯(DVB)为共聚单体制备了不同交联度的微米和亚微米窄分散聚合物微球,考查了共聚单体对球体的影响,并用扫描电镜(SEM)和红外光谱对微球进行了表征.