Microgel particles containing methacrylic acid: pH-triggered swelling behaviour and potential for biomaterial application

pH-responsive microgels are crosslinked polymer particles that swell when the pH approaches the pK(a) of the ionic monomer incorporated within the particles. In recent work from our group it was demonstrated that the mechanical properties of degenerated intervertebral discs (IVDs) could be restored to normal values by injection of poly(EA/MAA/BDDA) (ethylacrylate, methacrylic acid and butanediol diacrylate) microgel dispersions [J.M. Saunders, T. Tong, C.L. Le Maitre, T.J. Freemont, B.R. Saunders, Soft Matter 3 (2007) 486]. In this work we report the pH dependent swelling and rheological properties of poly(MMA/MAA/EGDMA) (methylmethacrylate and ethyleneglycol dimethacrylate) microgel dispersions. This system was investigated because it contains monomers that are already used as biomaterials. The poly(MMA/MAA/EGDMA) particles exhibit pH-triggered volume swelling ratios of up to ca. 250. The swelling onset for these particles occurs at pH values greater than ca. 6.0. A pK(a) for these particles of ca. 6.7 is consistent with titration and swelling data. Fluid-to-gel phase diagrams for concentrated poly(MMA/MAA/EGDMA) dispersions were determined as a function of polymer volume fraction and pH using tube-inversion measurements. The rheological properties for the gelled microgel dispersions were investigated using dynamic rheology measurements. The elastic modulus data for the poly(MMA/MAA/EGDMA) gelled dispersions were compared to data for poly(EA/MAA/BDDA) microgels. A similar pH-dependence for the elastic modulus was apparent. The maximum elastic modulus was achieved at a pH of about 7.0. The elastic modulus is an exponentially increasing function of polymer volume fraction at pH 7.0. Preliminary cell challenge experimental data are reported that indicate that gelled poly(MMA/MAA/EGDMA) microgel dispersions are biocompatible with cells from human intervertebral discs. However, the duration over which these experiments could be performed was limited by gradual redispersion of the gelled microgel dispersions. Based on the results presented it is suggested that poly(MMA/MAA/EGDMA) microgel would be a good candidate as a biomaterial for structural support of soft connective tissues.     

pH-responsive microgels containing hydrophilic crosslinking co-monomers: shell-exploding microgels through design

pH-responsive microgels are crosslinked polymer colloids that swell when the pH approaches the pK _a of the particles. They have potential application for injectable gels for tissue repair and drug delivery systems. This study focuses on the pH-triggered gelation behaviour of a series of poly (EA/MAA/X) microgels. EA and MAA are ethylacrylate and methacrylic acid. Here, we investigate the effect of crosslinking monomer type (X) on microgel properties. The crosslinking monomers used were poly (ethyleneglycol) dimethacrylate (PEGD), ethyleneglycol dimethacrylate (EGD) and butanediol diacrylate (BDD). The microgel containing PEGD (m-PEGD) is a new system. The microgel containing BDD (m-BDD) was used as a control system. The concentrated microgel dispersions formed physical gels when the pH was increased to 5.3?C6.7, and the polymer volume fractions (? _p ) were above about 0.05. Evidence from photon correlation spectroscopy (PCS) and dynamic rheology was presented for abrupt pH-triggered increases, and then decreases of the hydrodynamic diameters for m-PEGD and the microgel prepared using EGD (m-EGD). This appears to be tuneable through crosslinker structure. An unexpected gelation behaviour, which may involve a new gel state for microgels, was found for m-PEGD dispersions. Uniquely, those dispersions formed gels at pH values less than the microgel's pK _a . This behaviour was linked to an outer-shell electrostatic repulsive interaction. The data point to a phenomenon, whereby the m-PEGD shells appear to explode at pH values above 7.0. The control microgel prepared, using BDD (m-BDD), did not show any evidence of shell fragmentation at any pH. That microgel has potential as a model pH-responsive microgel system in that the properties measured by PCS and rheology agreed well. To probe that system in more detail, the rheological data for m-BDD was analysed using scaling theory. The variation of the storage modulus (G') with ? _p gave a scaling exponent of 2.0.     

Study of pH-responsive microgels containing methacrylic acid: effects of particle composition and added calcium

pH-responsive microgel dispersions contain cross-linked polymer particles that swell when the pH approaches the pKa of the ionic monomer incorporated within the particles. In recent work from our group, it was demonstrated that the mechanical properties of degenerated intervertebral discs (IVDs) could be restored to normal values by injection of pH-responsive microgel dispersions (Saunders, J. M.; Tong, T.; LeMaitre, C.; Freemont, A. J.; Saunders, B. R. Soft Matter 2007, 3, 486). These dispersions change from a fluid to a gel with increasing pH. The present work investigates the pH-dependent properties of dispersions of microgel particles containing MAA (methacrylic acid) and also the effects of added Ca2+. Two microgels are discussed: microgel A is poly(EA/MAA/AM) (EA and AM are ethyl acrylate and allyl methacrylate), and microgel B is poly(EA/MAA/BDDA) (butanediol diacrylate). The pH-dependent particle properties investigated include hydrodynamic diameters and electrophoretic mobilities. The critical coagulation concentrations (CCC) of dilute dispersions and the elastic modulus (G') of concentrated, gelled microgel dispersions were also investigated. In the absence of added Ca2+, the particle swelling and G' were smallest and largest, respectively, for microgel A. The changes in hydrodynamic diameter and mobility with pH were explained in terms of a core-shell swelling mechanism. Added Ca2+ was found to significantly decrease the CCCs, extents of particle swelling, and magnitude of the electrophoretic mobility. This was attributed to the ionic cross-linking of neighboring RCOO- groups by Ca2+. It is suggested that the formation of ionic cross-links is inefficient within the microgel particles because of the presence of covalent cross-links that oppose the large-scale conformational rearrangement of neighboring RCOO- groups. The effect of Ca2+ on the properties of the gelled dispersions is important from the viewpoint of potential application in vivo. Rheological studies of the gelled microgel dispersions showed that added Ca2+ did not have a specific influence on G'. The differences observed in the presence of Ca2+ were attributed to ionic strength effects (screening). The key parameter that controls G' of the gelled microgel dispersions is pH. The results from this work suggest that the elasticity of the gels would be slightly reduced in vivo as a consequence of the high ionic strength present.     

A study of poly(butadiene/methacrylic acid) dispersions: from pH-responsive behaviour to the effects of added Ca2+

This study investigates the effects of added Ca(2+) on the properties of poly(Bd/MAA) dispersions (1,3-butadiene and methacrylic acid) and considers the effect of particle composition on the pK(a). Four latex dispersions are considered in detail. These include poly(Bd/6MAA) and poly(Bd/20MAA) which contain, 6 and 20 wt% MAA, respectively, based on the total monomer mass used for dispersion preparation. Two model systems are also used for comparison. These are poly(Bd) and poly(EA/33MAA/BDDA) (EA and BDDA are ethyl acrylate and butanediol diacrylate). The latter is a well-studied model pH-responsive microgel. The apparent pK(a) of the poly(Bd/MAA) dispersions was determined from potentiometric titrations and found to increase with Bd content. The pH-dependence of the particle size was studied using photon correlation spectroscopy. Electrophoretic mobility measurements were also used. The hydrodynamic diameters and mobilities exhibited major changes as the pH approached the pK(a) for the particles. The critical coagulation concentrations were also measured. The results indicate that Ca(2+) caused pronounced dispersion instability at low pH. Moreover, Ca(2+) prevents swelling of the poly(Bd/MAA) particles at high pH. It was found that efficient ionic binding of all of the RCOO(-) groups within the poly(Bd/20MAA) particles occurred when the mole ratio of RCOO(-) to Ca(2+) was less than or equal to 2.0. Consideration of all the data leads to the suggestion that poly(Bd/MAA) particles have a core-shell structure. It is suggested that the particle core contains mostly poly(Bd) and that the shell is comprised of lightly crosslinked poly(Bd-co-MAA) copolymer.     

Functionalised Microgels for Acrylic Coatings

Summary: Aqueous acrylic dispersions of hydroxy-functionalised copolymer microgel particles crosslinked with allyl methacrylate were synthesized by emulsion polymerization. The microgels were investigated as reactive polymer fillers in mixtures with a water-borne film-forming dispersion. Properties of coatings cast from mixtures of aqueous dispersion of hard microgel particles and film-forming water-borne dispersion were investigated. The swelling behaviour of microgels in selected solvents (aliphatic ketones) as a function of microgel composition is discussed as well. It was found that the swelling ability of microgels decreased with growing degree of crosslinking. Microgels comprising copolymerised butyl methacrylate swelled less in aliphatic ketones than microgels without this comonomer. This work was focused mainly on the influence of microgels incorporated in the commercial solvent-borne acrylic binders on the properties of coatings. It was shown that the application of 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 the final hardness of coatings.     

On the structure of poly(N-isopropylacrylamide) microgel particles

This investigation presents a study of the internal structure of poly(NIPAM/xBA) microgel particles (NIPAM and BA are N-isopropylacrylamide and N,N'-methylene bisacrylamide, respectively). In this study, x is the wt % of BA used during microgel synthesis. Two values of x were used to prepare the microgels, 1 and 10. The microgel dispersions were investigated using photon correlation spectroscopy (PCS) and small-angle neutron scattering (SANS). These measurements were made as a function of temperature in the range 30-50 degrees C. Scattering maxima were observed for the microgels when the dispersion temperatures were less than their volume phase transition temperatures. The SANS data were fitted using a model which consisted of Porod and Ornstein-Zernike form factors. The analysis showed that the macroscopic hydrodynamic diameter of the microgel particles and the submicroscopic mesh size of the network are linearly related. This is the first study to demonstrate affine swelling for poly(NIPAM/xBA) microgels. Furthermore, the mesh size does not appear to be strongly affected by x. The data suggest that the swollen particles have a mostly homogeneous structure, although evidence for a thin, low segment density shell is presented. The study confirms that poly(NIPAM/xBA) microgel particles have a core-shell structure. The shell has an average thickness of approximately 20 nm for poly(NIPAM/1BA) particles which appears to be independent of temperature over the range studied. The analysis suggests that the particles contained approximately 50 vol % water at 50 degrees C. The molar mass of the poly(NIPAM/1BA) microgel particles was estimated as 6 x 10(9) g mol(-1).     

pH响应性P(MMA-co-MAA-co-HEMA)微凝胶的制备及其性能

利用预乳化乳液法制备了不同单体配比的聚(甲基丙烯酸甲酯-co-甲基丙烯酸-co-甲基丙烯酸羟乙酯)(P(MMA-co-MAA-co-HEMA))微凝胶分散液;采用透射电子显微镜、动态光散射仪研究了微凝胶的微观形态、粒径大小及其溶胀率;利用试管倒转法对微凝胶分散液的凝胶化相转变行为进行了研究,借助椎板流变仪考察了所形成胶态凝胶的储能模量与单体配比、微凝胶分散液浓度和温度的关系.结果表明,所制备的微凝胶的数均粒径为90 nm左右,当MMA与MAA的投料质量不变时,随着HEMA含量的增加,分散液凝胶化所需的临界最小浓度增大,临界最大pH值减小,胶态凝胶的储能模量增加.当保持单体MMA与HEMA的投料质量不变时,随着单体MAA投料质量的增多,微凝胶的数均粒径和溶胀率增大,胶态凝胶的储能模量先升高后降低;当MAA占单体总摩尔数的25%时,浓度为15 wt%的微凝胶分散液在扫描频率为100 rad/s时,胶态凝胶的储能模量最高可达2×104Pa.这类微凝胶分散液在组织工程支架材料方面有潜在的应用价值.     

Poly(N-vinylcaprolactam-co-glycidyl methacrylate) aqueous microgels labeled with fluorescent LaF3:Eu nanoparticles

We describe the synthesis and properties of functional microgel particles based on poly(N-vinylcaprolactam-co-glycidyl methacrylate) (PVCL/PGMA) copolymer. A series of colloidally stable microgel particles with a range of glycidyl methacrylate content were prepared by surfactant-free heterophase polymerization in water. The microgel particles obtained had hydrodynamic radii between 250 and 350 nm and were fairly monodisperse in size; however, a broadening of the particle size distribution was observed for samples with a low GMA content. The PVCL/PGMA microgel particles exhibit thermally responsive reversible changes in diameter in water, and the swelling degree increased with the PVCL fraction in the copolymer structure. These microgels were then modified with photoluminescent europium-doped lanthanum fluoride nanoparticles (LaF3:Eu-AEP) through reaction of the 2-aminoethyl phosphate surface ligands with epoxy groups present in the microgel. These hybrid microgels were colloidally stable and thermally responsive in aqueous solution.     

pH响应型P(HEMA/MAA)纳米微凝胶分散液的凝胶化行为和流变性能

制备了在修复受损组织方面有应用潜能的纳米级聚(甲基丙烯酸羟乙酯/甲基丙烯酸) (P(HEMA/MAA))微凝胶; 采用试管倒转法对不同pH值和浓度的P(HEMA/MAA)微凝胶分散液的凝胶化相转变行为进行了研究; 借助椎板流变仪考察了低浓度和高浓度微凝胶分散液的流变性能, 并对pH触发物理凝胶化相转变机理进行了推测. 结果表明: 在生理pH值环境下, 一定浓度的P(HEMA/MAA)微凝胶分散液可以发生凝胶化相转变形成凝胶态, pH=7时, HEMA/MAA进料摩尔比为8/2的微凝胶分散液凝胶化后得到的凝胶力学性能最佳, 最大弹性模量(G')可达7.58×10³ Pa; P(HEMA/MAA)微凝胶颗粒在不同条件下具有不同的溶胀效果, 导致低浓度分散液的表观粘度发生相应的变化, 并由此推测出微凝胶颗粒的溶胀过程由外及内, 分为三个阶段; 高浓度微凝胶分散液发生凝胶化相转变主要是由颗粒间或颗粒与分散介质间形成的空间静电稳定作用和氢键共同作用引起的.     

Thermodynamic considerations of microgel swelling behavior

A simple but novel thermodynamic model is presented, based upon van't Hoff analysis, for the reversible swelling behavior of colloidal microgels. The swelling, as a function of temperature, of poly(N-isopropylacrylamide/N,N'-methylenebisacrylamide) as well as poly(N-isopropylacrylamide/vinylpyridine/N,N'-methylenebisacrylamide) and poly(N-isopropylacrylamide/acrylic acid/N,N'-methylenebisacrylamide) microgel dispersions in H2O and D2O has been studied by photon correlation spectroscopy (PCS). PCS data was used to obtain the hydrodynamic diameter and hence the volume of the microgels (before and after reconstitution following freeze-drying) as a function of temperature. The choice of standard reference states, for analyzing the data attained, is discussed, and the one selected is that of the volume of the microgels at 333 K in H2O. For all microgels examined the volume, at this temperature, is shown to be independent of solvent (H2O, D2O). The derived data has allowed the exploration of a novel thermodynamic approach to the study of the swelling behavior of the microgels. The constant volume, at 333 K, for each of the polymer systems constituting the microgels is suggested to be an intrinsic property of the polymers themselves.     

Connection of poly(methyl methacrylate) microgel particles dispersed in poly(vinyl alcohol) matrix by seed polymerization

Poly(methyl methacrylate) microgels covered with poly(hydroxyethyl methacrylate) thin layer was dispersed in poly(vinyl alcohol) matrix. Homogeneous and regular arrangement of the microgel particles was suggested by Bragg diffraction for the films prepared by varying the PVA/microgel ratio (from 6/4 to 3/7 (w/w)). It was proved that the regular arrangement and connection of the microgels by seeded polymerization in poly(vinyl alcohol) were possible. © 1996 John Wiley & Sons, Inc.     

Thermosensitive phase behavior and drug release of in situ gelable poly(N-isopropylacrylamide-co-acrylamide) microgels

In situ gelable poly(N-isopropylacrylamide-co-acrylamide) microgels were prepared by precipitation polymerization in the presence of various amounts of N,N′-methlenebisacrylamide as a crosslinker. The diameters of microgels were in the range of 200–300 nm with narrow distributions as determined by photo correlation spectroscopy. The equilibrium swelling ratio and thermosensitive properties of the microgels increased with decreasing crosslinker content. The volume phase transition of microgels dispersions at high concentrations were investigated by phase diagrams. The microgels dispersions experienced four phases when the temperature was increased: semitranslucent swollen gel, clear flowable suspension, cloud flowable suspension, and white shrunken gel. The related phase transition temperatures were influenced by crosslinker content and the concentration of the microgel dispersions. Herein, the gelation temperature was changed by more than 20 °C, shrinking temperatures were slightly changed by about 3 °C, and cloud point temperatures showed almost no change. The three phase transition temperatures of microgels dispersed in phosphate-buffered saline solutions were lower than that in water. As drug carriers, the release rates of bleomycin from bleomycin-loaded microgel dispersions exhibited diffusion control at human body temperature.     

Swelling behavior of PMMA-g-PEO microgel particles by organic solvents

Aqueous dispersions of cross-linked poly(methylmethacrylate)-g-poly(ethylene oxide) [PMMA-g-PEO] microgel particles have been prepared from mixtures of methylmethacrylate [MMA] and MMA-PEO macromonomer, with ethylene glycol dimethacrylate [EGDM] as the cross-linking monomer (0.2-0.5% wt%). The hydrodynamic radius of these (unswollen) microgel particles ranged from 73 to 85 nm, and the particles were essentially monodisperse with regard to their size distribution. Their swelling behavior has been investigated in the presence of both water-miscible and water-immiscible organic solvents. In general, with the addition of a water-miscible solvent, deswelling behavior was observed. However, the microgel particles were swollen on addition of 1,4-dioxan, which is a good solvent for PMMA. With water-immiscible organic solvents, the extent of swelling depended on the solvency properties of the organic liquid for PMMA. In the presence of benzene, the somewhat large increases in particle size have been attributed to weak flocculation. This has been assumed from an estimate of the van der Waals attraction energy between the swollen microgel particles.     

Study on soap‐free P(MMA‐EA‐AA or MAA) latex particles with narrow size distribution

Soap‐free poly(methyl methacrylate‐ethyl acrylate‐acrylic acid or methacrylic acid) [P(MMA‐EA‐AA or MAA)] particles with narrow size distribution were synthesized by seeded emulsion polymerization of methyl methacrylate (MMA), ethyl acrylate (EA) and acrylic acid (AA) or methacrylic acid (MAA), and the influences of the mass ratio of core/shell monomers used in the two stages of polymerization ([C/S]_w) and initiator amount on polymerization, particle size and its distribution were investigated by using different monomer addition modes. Results showed that when the batch swelling method was used, the monomer conversion was more than 96.0% and particle size distribution was narrow, and the particle size increased first and then remained almost unchanged at around 600 nm with the [C/S]_w decreased. When the drop‐wise addition method was used, the monomer conversion decreased slightly with [C/S]_w decreased, and large particles more than 750 nm in diameter can be obtained; with the initiator amount increased, the particle size decreased and the monomer conversion had a trend to increase; the particle size distribution was broader and the number of new particles was more in the AA system than in the MAA system; but the AA system was more stable than the MAA system at both low and high initiator amount. Copyright © 2006 John Wiley & Sons, Ltd.     

Polar Gradient Latex Particles with Hydrophilic Core and Hydrophobic Shell Prepared via Multistep Emulsion Polymerization

Monodisperse polar gradient particles were synthesized via a three‐step emulsion polymerization using poly(butyl acrylate‐methyl methacrylate‐methacrylic acid‐ethylene glycol dimethacrylate) (P(BA‐MMA‐MAA‐EGDMA)) as core, poly(methyl methacrylate‐methacrylic acid‐styrene) (P(St‐MMA‐MAA)) as interlayer and polystyrene (PSt) as shell. The particle growth and encapsulation in each emulsion polymerization step were followed by transmission electron microscopy (TEM), dynamic light scattering (DLS) and conductometric titration. Results indicated that the feeding mode and the interlayer were essential to prepare the polar gradient latex particles with hydrophilic core and hydrophobic shell. The morphologies of the two‐layer core/interlayer and three‐layer core/interlayer/shell particles were observed in TEM micrographs, and the sequential encapsulations of the carboxyl‐containing core and the core/interlayer particles were confirmed by an increase in the particle size as well as an increase in the buried carboxyl percentage.     

Synthesis and aqueous solution properties of sterically stabilized pH-responsive polyampholyte microgels

Emulsion copolymerization of poly(methacrylic acid) and poly(2-(diethylamino)ethyl methacrylate) (PMAA/PDEA) yielded pH-responsive polyampholyte microgels of 200-300 nm in diameter. These microgels showed enhanced hydrophilic behavior in aqueous medium at low and high pH, but formed large aggregates of approximately 2500 nm at intermediate pH. To achieve colloidal stability at intermediate pH, a second batch of microgels of identical monomer composition were synthesized, where monomethoxy-capped poly(ethylene glycol)methacrylate (PEGMA) was grafted onto the surface of these particles. Dynamic light-scattering measurements showed that the hydrodynamic radius, Rh, of sterically stabilized microgels was approximately 100 nm at intermediate pH and increased to 120 and 200 nm at pH 2 and 10, respectively. Between pH 4 and 6, these microgels possessed mobility close to zero and a negative second virial coefficient, A2, due to overall charge neutralization near the isoelectric pH. From the Rh, mobility, and A2, cross-linked MAA-DEA microgels with and without PEGMA retained their polyampholytic properties in solution. By varying the composition of MAA and DEA in the microgel, it is possible to vary the isoelectric point of the colloidal particles. These new microgels are being explored for use in the delivery of DNA and proteins.     

A new family of water-swellable microgel particles

In this study a new family of microgel particles is investigated which contain methylmethacrylate (MMA), ethylacrylate (EA), acrylic acid (AA), glycerol propoxytriacrylate (GPTA), and Emulsogen (Em). GPTA is a trifunctional crosslinking monomer, whereas Em is a polymerisable alcohol ethoxylate surfactant. TEM and PCS data reveal that the extent of microgel swelling originates from a pH-independent contribution (due to Em) as well as a pH-dependent contribution (due to AA). The major contribution to swelling comes from pH-independent swelling. Consideration of the equations governing particle swelling allows the effective pK(a) of the incorporated AA groups to be estimated. There is evidence of a shift of the pK(a) for the AA groups from 4.5 to ca. 9.5 when the microgel particles containing AA also contain Em. This suggests intraparticle hydrogen bonding between AA and ethylene oxide segments at low pH.     

交联剂对无皂P(MMA-EA-MAA)种子聚合乳胶粒成孔的影响

采用完全无皂种子乳液聚合技术合成了粒径窄分布的P(MMA-EA-MAA)乳胶粒,通过对上述胶乳进行碱处理,制备出了具有空腔结构和多孔结构的聚合物乳胶粒,研究了交联剂的种类和用量对聚合过程、胶粒特性及胶粒结构形态的影响.结果表明,体系中加入交联剂后,单体转化率都有不同程度的提高;随交联剂用量的增加,乳胶粒粒径略有减小,交联剂用量较高时,乳胶粒粒径分布加宽;二乙烯基苯(DVB)的交联效率稍高于双甲基丙烯酸乙二醇酯(EGDMA);不加入交联剂及EGDMA用量低于0.5%时,处理后乳胶粒呈空腔结构,加入DVB及EGDMA用量高于1.0%时,处理后乳胶粒呈多孔结构,并且乳胶粒体积增量随交联剂用量的增加而减小.     

Synthesis and characterization of novel pH-responsive microgels based on tertiary amine methacrylates

Emulsion polymerization of 2-(diethylamino)ethyl methacrylate (DEA) in the presence of a bifunctional cross-linker at pH 8-9 afforded novel pH-responsive microgels of 250-700 nm diameter. Both batch and semicontinuous syntheses were explored using thermal and redox initiators. Various strategies were evaluated for achieving colloidal stability, including charge stabilization, surfactant stabilization, and steric stabilization. The latter proved to be the most convenient and effective, and three types of well-defined reactive macromonomers were examined, namely, monomethoxy-capped poly(ethylene glycol) methacrylate (PEGMA), styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (PDMA50-St), and partially quaternized styrene-capped poly[2-(dimethylamino)ethyl methacrylate] (10qPDMA50-St). The resulting microgels were pH-responsive, as expected. Dynamic light scattering and 1H NMR studies confirmed that reversible swelling occurred at low pH due to protonation of the tertiary amine groups on the DEA residues. The critical pH for this latex-to-microgel transition was around pH 6.5-7.0, which corresponds approximately to the known pKa of 7.0-7.3 for linear PDEA homopolymer. The microgel particles were further characterized by electron microscopy and aqueous electrophoresis studies. Their swelling and deswelling kinetics were investigated by turbidimetry. The PDEA-based microgels were compared to poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) microgels prepared with identical macromonomer stabilizers. These PDPA-based microgels had a lower critical swelling pH of around pH 5.0-5.5, which correlates with the lower pKa of PDPA homopolymer. In addition, the kinetics of swelling for the PDPA microgels was somewhat slower than that observed for PDEA microgels; presumably this is related to the greater hydrophobic character of the former particles.     

Synthesis and characteristics of poly(methyl methacrylate‐co‐methacrylic acid)/poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive semi‐hollow latex particles and their application to drug carriers

In this work, the poly(methyl methacrylate‐co‐methacrylic acid)/poly(methacrylic acid‐co‐N‐isopropylacrylamide) thermosensitive composite semi‐hollow latex particles was synthesized by three processes. The first process was to synthesize the poly(methyl methacrylate‐co‐methacrylic acid) (poly (MMA‐MAA)) copolymer latex particles by the method of soapless emulsion polymerization. The second process was to polymerize methacrylic acid (MAA), N‐isopropylacrylamide (NIPAAm), and crosslinking agent, N,N′‐methylenebisacrylamide, in the presence of poly(MMA‐MAA) latex particles to form the linear poly(methyl methacrylate‐co‐methacrylic acid)/crosslinking poly(methacrylic acid‐co‐N‐isopropylacrylamide) (poly(MMA‐MAA)/poly(MAA‐NIPAAm)) core–shell latex particles with solid structure. In the third process, part of the linear poly(MMA‐MAA) core of core–shell latex particles was dissolved by ammonia to form the poly(MMA‐MAA)/poly(MAA‐NIPAAm) thermosensitive semi‐hollow latex particles. The morphologies of the semi‐hollow latex particles show that there is a hollow zone between the linear poly(MMA‐MAA) core and the crosslinked poly(MAA‐NIPAAm) shell. The crosslinking agent and shell composition significantly influenced the lower critical solution temperature of poly(MMA‐MAA)/poly(MAA‐NIPAAm) semi‐hollow latex particles. Besides, the poly(MMA‐MAA)/poly(MAA‐NIPAAm) thermosensitive semi‐hollow latex particles were used as carriers to load with the model drug, caffeine. The processes of caffeine loaded into the semi‐hollow latex particles appeared four situations, which was different from that of solid latex particles. In addition, the phenomenon of caffeine released from the semi‐hollow latex particles was obviously different from that of solid latex particles. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3441–3451