Characterization of microgels by Brookfield viscometry with cylindrical,T‐bar,and flags impeller spindles

Neutralized 0.5% microgels of the crosslinked copolymer of methyl vinyl ether and maleic anhydride were characterized by the penetrating ball test and by Brookfield viscometry with the # 7 cylindrical, T‐E, and flag‐impeller spindles. Apparent wall slip between the microgel and the #7 cylindrical spindle is a surface phenomenon that is more pronounced for “hard” microgels than for “soft” microgels and depends strongly on the interaction between the surface of the spindle and the microgel. Apparent wall slip can be enhanced by coating the #7 spindle with hydrophobic polymers and polymers with carboxyl groups and suppressed by coating the spindle with vinylpyrrolidone‐based polymers. Similar apparent wall slip was also noticed for the cross‐linked polyacrylic acid microgel. Apparent wall slip was not noticed when the T‐E spindle and the flag‐impeller spindle were used in viscosity measurement. The viscosity of microgels measured with a #7 spindle coated with polyvinylpyrrolidone, a T‐E spindle, and a flag‐impeller spindle correlate well with each other, indicating that the apparent wall slip is suppressed equally well by these three spindles. A simple penetrating ball test was used to differentiate hard microgels from soft microgels. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 67–74, 1999     

Ethylcellulose microparticles containing chitosan and gelatin: pH-dependent release caused by complex coacervation

Ethylcellulose microparticles containing chitosan and gelatin were prepared by spray drying water-in-oil (W/O) emulsion. Water phase was chitosan:gelatin solution in distilled water, and oil phase was ethylcellulose solution in dichloromethane. FITC-dextran was included in water phase as a fluorescence dye. The maximum coacervation was observed at pH 6.0 when the ratio of chitosan to gelatin was 1:15. Microparticles containing chitosan and gelatin in the ratio showed a higher release under acidic condition (e.g. pH 4.0) and neutral condition (e.g. pH 7.0), but a lower release at pH 5.0 and pH 6.0. The complex coacervate composed of chitosan and gelatin was efficiently formed at those pHs, and the formation of coacervate would be responsible for the lower release.     

Thermo‐ and pH‐responsive microgels for controlled release of insulin

Microgel particles were prepared, made of hydroxypropylcellulose‐graft‐(acrylic acid) (HPC‐g‐AA) and acrylic acid(AA). The particles undergo reversible volume phase transitions in response to both pH and temperature changes while keeping the inherent properties of PAA and HPC‐g‐AA. Dynamic light scattering measurements reveal that the average hydrodynamic radius and hydrodynamic radius distributions of the microgel particles depend on temperature and pH. The microgels exhibit excellent pH sensitivity and a higher swelling ratio at higher pH in aqueous solution. In vitro release study shows that the amount of insulin released from the microgels is less at pH = 1.2 than at pH = 6.8. The results indicate that the resultant microgels seem to be of great potential for intelligent oral drug delivery. Copyright © 2012 Society of Chemical Industry     

多重响应壳聚糖微凝胶的制备及溶胀性

采用无皂乳液聚合法制备聚(N-异丙基丙烯酰胺)/壳聚糖微凝胶(PNIPAM/CS),透射电镜和动态光散射研究了微凝胶外貌形态及刺激响应性。结果显示,微凝胶颗粒呈球形,具有核、壳结构形态。加入壳聚糖对PNIPAM的体积相转变温度(VPTT)有影响,微凝胶VPTT随壳聚糖用量的增加向高温迁移,此结果与示差量热法(DSC)测定一致。不同pH条件下微凝胶粒径变化表明,颗粒直径随pH增大逐渐减小,至碱性又增大,显示明显的pH敏感性;相应颗粒Zeta电位逐渐减小,接近中性达到等电点,至碱性反转为负值,这一变化能对微凝胶pH敏感性进行合理解释。     

Silver nanoparticles containing hybrid polymer microgels with tunable surface plasmon resonance and catalytic activity

Multi-responsive poly(N-isoprpylacrlamide-methacrylic acid-acrylamide) [P(NIPAM-MAA-AAm)] copolymer microgel was prepared by free radical emulsion polymerization. Silver nanoparticles were fabricated inside the microgel network by in-situ reduction of silver nitrate. Swelling and deswelling behavior of the pure microgels was studied under various conditions of pH and temperature using dynamic light scattering. A red shift was observed in surface plasmon resonance wavelength of Ag nanoparticles with pH induced swelling of hybrid microgel. The catalytic activity of the hybrid system was investigated by monitoring the reduction of p-nitrophenol under different conditions of temperature and amount of catalysts. For this catalytic reaction a time delay of 8 to 10min was observed at room temperature, which was reduced to 2 min at high temperature due to swelling of microgels, which facilitated diffusion of reactants to catalyst surface and increased rate of reaction.     

Multi‐responsive microgel of a water‐soluble monomer via emulsion polymerization

Microgel of a water‐soluble monomer [2‐(N‐morpholino)ethyl methacrylate (MEMA)] was successfully prepared in aqueous media via emulsion polymerization by using a novel water‐soluble block copolymer as stabilizer. Characterization studies confirmed monodisperse spherical morphologies of microgels with a diameter of 280 nm at neutral pH. These microgels exhibited multi‐responsive behavior by responding solution pH, temperature, ionic strength, type of dispersing media, and magnetic particles. It swells well at low pH (<6.0) and at low temperature, but shrinks above pH 6.0, or even more shrinks with salt addition at neutral and basic conditions. In addition, the hydrodynamic diameter of PMEMA microgel was decreased gradually at basic and neutral pH when solution temperature was increased up to the lower critical solution temperature of PMEMA (LCST, 35°C), but microgel diameter did not change much above LCST. Multi‐responsive behavior of PMEMA microgel was investigated by using dynamic light scattering, UV‐Vis spectrophotometer and zeta potentiometer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42072.     

Preparation and characterization of pH-sensitive hydrogel microparticles as a biological on–off switch

The pH-responsive swelling and release behaviors of anionic P(MAA-co-EGMA) hydrogel microparticles having various MAA and EG contents were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. When DC was used as a dispersion stabilizer, well-dispersed hydrogel microparticles having an average diameter of approximately 4 μm were obtained. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-co-EGMA) hydrogels at a pH of around 5, which is the pK _a of PMAA. When the MAA content in the hydrogel increased, the swelling ratio increased at a pH above 5 due to the more electrostatic repulsion between the charged groups of MAA. The P(MAA-co-EGMA) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) small amounts of Rh-B were released while at high pH (pH 6.0) relatively large amounts of Rh-B were released from the hydrogels. The difference in the released amount of Rh-B from the hydrogels between pH 4.0 and 6.0 decreased when the MAA content in the hydrogels decreased, which means that the pH-responsive release behavior of the P(MAA-co-EGMA) hydrogel microparticles is closely related to the pH-responsive swelling property of the hydrogel.     

pH值对N-异丙基丙烯酰胺与甲基丙烯酸共聚形成微凝胶的影响

在pH值为4．0和7．0的水介质中分别采用乳液聚合法使N-异丙基丙烯酰胺（NIPAM）和甲基丙烯酸（MAA）共聚,合成了具有温度／pH双重刺激响应性的P（NIPAM—CO—MAA）共聚微凝胶。傅立叶红外变换光谱、元素分析和电位滴定分析结果表明,在pH为4．0条件下合成的微凝胶中MAA单元含量偏高,微凝胶的粒径随着MAA用量的增加而增大,而pH为7．0时合成的微凝胶的粒径随着单体MAA用量的增加而减小。通过动态激光光散射测试P（NIPAM—CO—MAA）微凝胶的动力学直径随介质温度或pH值的变化关系发现,pH为4．0条件下合成的微凝胶具有更明显的pH刺激响应性,其温度刺激响应性受介质pH值的影响较大,表明MAA单元有可能更均匀地分布于微凝胶聚合物网络中。     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Fabrication and characterization of microgel-impregnated, thermosensitive PNIPAAm hydrogels

Poly(N-isopropylacrylamide)/poly(ethylene glycol) diacrylate (PNIPAAm/PEG-DA) microgels were used as an additive during the polymerization and/or crosslinking of PNIPAAm hydrogels to improve their thermosensitive properties. The influence of this additive on the property of resulting PNIPAAm hydrogels was investigated and characterized. The interior morphology by scanning electron microscopy (SEM) revealed that microgel impregnated PNIPAAm hydrogels have tighter and constrained porous network structures, although large cavities of 30-40 μm in diameter, occupied by the microgels were sporadically distributed in this constrained network. Differential scanning calorimetry (DSC) studies did not show apparent difference in lower critical solution temperature (LCST) between normal and microgel-impregnated PNIPAAm hydrogels. The incorporating of PNIPAAm/PEG-DA microgels, however, significantly improved mechanical properties of modified hydrogels when comparing with a normal PNIPAAm hydrogel, although the tendency was not strictly proportional to the microgel amount. Based on the temperature-induced swelling ratio data as well as response kinetics, microgel-impregnated hydrogels exhibited improved thermosensitive characteristics in terms of higher equilibrium swelling ratio as well as faster response rates and the level of improvement depended on the amount of microgel impregnated.     

Swelling of acrylic microgels in aliphatic ketones

The paper deals with the swelling behaviour of hydroxyl-functionalised microgels in the presence of aliphatic ketones. The copolymer microgels with different cross-linking densities were synthesized by the semi-batch emulsion copolymerisation of methyl methacrylate, butyl methacrylate, 2-hydroxyethyl methacrylate and allyl methacrylate. The extent of microgel particles swelling was evaluated using the dynamic light scattering, the potentiometric titration of accessible hydroxyl groups and the solvent-uptake measurements. It was found that the swelling ability of microgels decreased with growing degree of cross-linking. Microgels comprising copolymerised butyl methacrylate swelled less in utilised aliphatic ketones than microgels without this comonomer. Among all the investigated solvents, acetone was found to be the strongest solvent, while 5-methyl-2-hexanone (methyl isopentyl ketone) was shown to be the weakest one. Further, the microgels were investigated as reactive network precursors in a commercial thermosetting solvent-borne acrylic binder. It was shown that the application of functionalised microgels that were redispersed in acetone did not affect the surface appearance and transparency of coatings. Moreover, the presence of microgel network precursors accelerated film curing at ambient temperature and improved final hardness of coatings.     

Application of syndiotacticity‐rich PVA hydrogels prepared at a low temperature to thermo‐ and pH‐responsive release devices

Three kinds of physically cross‐linked syndiotacticity‐rich poly(vinyl alcohol) (s‐PVA) hydrogels were prepared at 0°C with use of the buffer solutions (BS) of pHs 4.0, 7.4, and 9.0. Three gels swelled at first and then began to shrink after 12 h when they were dipped in the same BS for preparation at higher temperature than 0°C. The release of Brilliant Blue (3 mg/1 mL) from the cylindrical gels prepared using BS of pH 7.4 was studied at 27, 37, and 47°C. Brilliant Blue has been released spending 4–12 h almost completely. The rate of release from the gel at temperatures of 27, 37, and 47°C became large with increasing temperature. The main factor on release of Brilliant Blue is not the contraction of gel, but swelling, because the degree of swelling (DS) became large with increasing temperatures for 27, 37, and 47°C. The rate of release from the gel (pH 4.0) was larger than that (pH 7.4) due to the increased DS of the hydrogel in early step at pH of 4.0. The apparent diffusion exponents of these releases at pH 7.4 evaluated from first 60% of the fractional release were lower than 0.45 due to the swelling during release. The exponent at pH 4.0 was 0.45 due to immediate swelling. The on‐off of shrinking behavior of atactic PVA (a‐PVA) hydrogel was observed under several temperature changes. The rate of release of Brilliant Blue at 5°C was lower than that at 27°C and no change was observed at 5°C after one on‐off cycle. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 41–46, 2000     

γ‐Irradiation preparation of poly(acrylic acid)–chitosan hydrogels for in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a γ‐irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid (AAc) content increased. The equilibrium swelling studies of hydrogels prepared under various conditions were carried out in an aqueous solution, and the pH sensitivity in a range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30 kGy dose of radiation. In addition, an increase of the degree of swelling with an increase in the pH was noticed and it had the highest value at pH 12. The drug 5‐fluorouracil was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at intestinal pH and the rest of the drug was released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3270–3277, 2003     

Preparation of poly(acrylic acid)–chitosan hydrogels by gamma irradiation and in vitro drug release

Biocompatible and biodegradable pH‐responsive hydrogels based on poly(acrylic acid) (AAc) and chitosan were prepared for controlled drug delivery. These interpolymeric hydrogels were synthesized by a gamma irradiation polymerization technique. The degree of gelation was over 96% and increased as the chitosan or acrylic acid content increased. The equilibrium swelling studies of hydrogels prepared in various conditions were carried out in an aqueous solution, and the pH sensitivity in the range of pH 1–12 was investigated. The AAc/chitosan hydrogels showed the highest water content when the 30 vol % AAc and 0.1 wt % chitosan were irradiated with a 30‐kGy radiation dose. Also, an increase of swelling degree with an increase in the pH was noticed and showed the highest value at pH 12. The drug, 5‐fluorouracil, was loaded into these hydrogels and the release studies were carried out in simulated gastric and intestinal fluids. The in vitro release profiles of the drugs showed that more than 90% of the loaded drugs were released in the first 1 h at the intestinal pH and the rest of the drug had been released slowly. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3660–3667, 2003     

Thermo-sensitive poly(N-vinylcaprolactam-co-acetoacetoxyethyl methacrylate) microgels. 3. Incorporation of polypyrrole by selective microgel swelling in ethanol-water mixtures

Behaviour of temperature-sensitive core-shell VCL/AAEM microgels has been studied in binary alcohol/water mixtures. Amount of alcohol in binary mixture influences strongly the swelling and thermo-sensitive properties of microgels. Alcohol induces swelling of VCL-rich microgel shell leading to larger dimensions of microgel particles and larger surface area. Under these conditions pyrrole polymerization was carried out, and the influence of pyrrole concentration, oxidant nature and temperature on morphology and properties of composite particles was investigated. Contrary to the polymerization in water medium, this selective swelling method gives possibility to increase three times loaded polypyrrole amount and maintain the stability of the colloidal system. It was found that in case when persulfate was applied as oxidant it is possible to vary effectively the particle size of composite microgels by changing the ethanol concentration in water. Contrary, when FeCl₃ was used as oxidant formation of secondary particles was detected leading to dispersions with bimodal particle size distribution. The conductivity of the composite particles was much higher if polypyrrole synthesis was carried out in pure water.     

pH‐sensitive swelling and release behaviors of anionic hydrogels for intelligent drug delivery system

The pH‐sensitive swelling and release behaviors of the anionic P(MAA‐co‐EGMA) hydrogels were investigated as a biological on–off switch for the design of an intelligent drug delivery system triggered by external pH changes. There was a drastic change of the equilibrium weight swelling ratio of P(MAA‐co‐EGMA) hydrogels at a pH of around 5, which is the pK_a of poly (methacrylic acid) (PMAA). At a pH below 5, the hydrogels were in a relatively collapsed state but at a pH higher than 5, the hydrogels swelled to a high degree. When the molecular weight of the pendent poly(ethylene glycol) (PEG) of the P(MAA‐co‐EGMA) increased, the swelling ratio decreased at a pH higher than 5. The pK_a values of the P(MAA‐co‐EGMA) hydrogels moved to a higher pH range as the pendent PEG molecular weight increased. When the feed concentration of the crosslinker of the hydrogel increased the swelling ratio of the P(MAA‐co‐EGMA) hydrogels decreased at a pH higher than 5. In release experiments using Rhodamine B (Rh‐B) as a model solute, the P(MAA‐co‐EGMA) hydrogels showed a pH‐sensitive release behavior. At low pH (pH 4.0) a small amount of Rh‐B was released while at high pH (pH 6.0) a relatively large amount of Rh‐B was released from the hydrogels. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

pH sensitive interpenetrating network microgels of sodium alginate‐acrylic acid for the controlled release of ibuprofen

pH‐Sensitive interpenetrating network (IPN) microgels (MGs) of sodium alginate (NaAlg) and acrylic acid have been prepared by using water‐in‐oil (W/O) emulsion technique. The MGs were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X‐ray diffractometer (X‐RD). The release of ibuprofen (IB), an anti‐inflammatory drug, from these MGs was studied in pH 1.2 and 7.4 media. MG network consists of NaAlg, which disintegrates in the intestinal fluid, while poly(acrylic acid) provides pH‐sensitivity to the microgel network. The system developed in this study showed a pH‐sensitivity for the release of IB, which was attributed to the diffusion controlled release of the drug through the surfaces of MGs that undergo disintegration after swelling, depending upon the chemical composition of MGs and pH of the medium. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006     

Responsive Hybrid Polymeric/Metallic Nanoparticles for Catalytic Applications

The aims of the current study were to synthesize new responsive polymeric microgels with embedded silver nanoparticles and then to employ these particles as catalyst for reduction reactions. To these ends, stimuli‐responsive microgels from PNIPAAm and the chitosan derivative were firstly synthesized by free radical precipitation polymerization. Then, silver nanoparticles were synthesized inside these microgel networks by in situ reduction of AgNO₃. These microgels were temperature/pH sensitive with a phase transition temperature of 32–35 °C in water at pH = 3 and 8, respectively. The catalytic activity of the Ag nanoparticles for the reduction of 4‐nitrophenol can be tuned through the swelling or collapse of the responsive microgel network hosting the active nanoparticles.

     

Synthesis and characterization of pH-sensitive and biodegradable hydrogels prepared by γ irradiation using microbial poly(γ-glutamic acid) and poly(ϵ-lysine)

Poly(γ-glutamic acid) (PGA) and poly(?-lysine) (PL) solutions were used as components to prepare mixed hydrogels by γ irradiation. A PGA and PL mixed solution was crosslinked to form a hydrogel with specific water content (weight of absorbed water/weight of dry gel) of 10–100 when the 5 wt % solution of mixed polymer was exposed to γ radiation of 87 kGy dosage under N₂ atmosphere. The specific water content increased with increasing PGA content of the PGA/PL mixed gel. The influence of pH and salt concentration on equilibrium swelling was studied. A characteristic pH-sensitive swelling behavior was obtained using compositional changes of PGA and PL in the gel. PGA/PL 50/50 wt % mixed gel swelling in acid (pH < 4.0) and alkaline (pH > 6.0) conditions and was deswelled between pH 4.0 and 6.0 due to the ionic composition changes of the gel network. With an increase in the ratio of PGA to PL, the hydrogels showed increasing sensitivity to salt solutions (NaCl, Na₂SO₄, and CaCl₂). In addition, degradation of PGA/PL gel by protease produced from Aspergillus oryzae was investigated at 40°C and pH 7.0. PL gel was degraded completely within 2 days. An increase in the ratio of PAG in the PGA/PL mixed gel led to a decrease in the degree of degradation as expected. Some subtle degradation changes were found in the 50/50 and 80/20 wt % (PGA/PL) gels that were degraded by only 3.5 and 3.8% by protease, respectively. © 1995 John Wiley & Sons, Inc.     

Swelling behavior of pectin/chitosan complex films

The swelling behavior of the complex film formed from pectin and chitosan was studied. The swelling degree increased sharply in the case of pH less than 2 and larger than 7. The swelling mechanisms of the complex film in acidic and alkaline medium are discussed, respectively. Moreover, the swelling degree could be modulated by means of the weight ratio of pectin to chitosan and the original weight concentration of pectin aqueous solution. © 1996 John Wiley & Sons, Inc.