A novel temperature and pH dual‐responsive hybrid hydrogel with polyhedral oligomeric silsesquioxane as crosslinker: synthesis,characterization and drug release properties

Octavinyl polyhedral oligomeric silsesquioxane (OVPS) is used as the crosslinker instead of N,N′‐methylenebisacrylamide (BIS) to copolymerize with 2‐(dimethylamino)ethyl methacrylate (DMAEMA) or DMAEMA and N‐isopropylacrylamide (NIPAM) to prepare hybrid hydrogels: P(OVPS‐co‐DMAEMA) and P(OVPS‐co‐DMAEMA‐co‐NIPAM). The prepared hydrogels are transparent and show dual response to temperature and pH. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X‐ray diffraction, differential scanning calorimetry, thermogravimetric analysis, dynamic mechanical analysis and tensile tests. Their mechanical properties, swelling ratio, deswelling and reswelling behaviors as well as drug release properties were investigated. The results indicate that OVPS can be incorporated into polymer networks in proportion to feed ratios. The P(OVPS‐co‐DMAEMA) hydrogel exhibits more homogeneous interior structure, higher swelling ratio and faster response than the conventional hydrogel prepared with BIS. Moreover, the incorporation of OVPS enhances the compression and tensile properties of the hydrogels. The feed ratios of OVPS and NIPAM have a great effect on volume phase transition temperature, thermal sensitivity, swelling behavior, mechanical properties and drug release properties of the hybrid hydrogels. The prepared dual‐responsive OVPS‐containing hydrogels are expected to be used as biomedical materials in drug release and tissue engineering. © 2014 Society of Chemical Industry     

Synthesis and characterization of poly{N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid} hydrogels for drug delivery

A novel pH‐sensitive hydrogel system composed of itaconic acid (IA) and N‐[3‐(dimethylamino) propyl] methacrylamide was designed. This system was prepared by aqueous copolymerization with N,N‐methylene bisacrylamide as a chemical crosslinker. The chemical structure of the hydrogels was characterized by Fourier transform infrared (FTIR) spectroscopy. The microstructure and morphology of the hydrogels were evaluated by X‐ray diffraction (XRD) and scanning electron microscopy (SEM). The SEM study of hydrogels on higher magnification revealed a highly porous morphology with uniformly arranged pores ranging from 40 to 200 μm in size. XRD analysis revealed the amorphous nature of the hydrogels, and it was found that an increase in the IA content in the monomer feed greatly reduced the crystallinity of the hydrogels. Swelling experiments were carried out in buffer solutions at different pH values (1.2–10) at 37°C ± 1°C to investigate their pH‐dependent swelling behavior and dimensional stability. An increase in the acid part (IA) increased the swelling ratio of the hydrogels. Temperature‐sensitive swelling of the hydrogels was investigated at 20–70°C in simulated intestinal fluid. The hydrogels swelled at higher temperatures and shrank at lower temperatures. 5‐Aminosalicylic acid (5‐ASA) was selected as a model drug, and release experiments were carried out under simulated intestinal and gastric conditions. 5‐ASA release from the poly N‐[3‐(dimethylamino) propyl] methacrylamide‐co‐itaconic acid‐80 (PDMAPMAIA‐80) hydrogel was found to follow non‐Fickian diffusion mechanism under gastric conditions, and a super case II transport mechanism was found under intestinal conditions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Gelatin based pH‐sensitive hydrogels for colon‐specific oral drug delivery: Synthesis,characterization, and in vitro release study

Based on gelatin (Gltn) and acrylic acid (AAc), biodegradable pH‐sensitive hydrogel was prepared using gamma radiation as super clean source for polymerization and crosslinking. Incorporation of PAAc in the prepared hydrogel was confirmed by Fourier transform infrared spectroscopy (FTIR). The effect of PAAc content on the morphological structure of the prepared hydrogel swollen at pH 1, 5, and 7 was examined using scanning electron microscopy (SEM). The results showed the dependence of the porous structure of the prepared hydrogels on AAc content and the pH of the swelling medium. Swelling properties of gelatin/acrylic acid copolymer hydrogels with different AAc contents were investigated at different pH values. Swelling data showed that the prepared hydrogels possessed pronounced pH sensitivity. In vitro release studies were performed to evaluate the hydrogel potential as drug carrier using ketoprofen as a model drug. Experimental data showed that the release profile depends on both hydrogel composition and pH of the releasing medium. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and characterization of novel cationic copolymer hydrogels with pH sensitivity and thermosensitivity

Cationic hydrogels were synthesized through the copolymerization of N‐isopropylacrylamide and dimethylaminoethylmethacrylate. N,N′‐Methylenebisacrylamide was used as a crosslinking agent, and sodium bisulfite/ammonium persulfate was used as an initiator. The equilibrium and dynamic swelling properties were investigated to reveal the pH sensitivity and thermosensitivity of the hydrogels. The conclusion was drawn that the prepared cationic hydrogels demonstrated critical sensitivity at 37°C and pH 7.0–8.0 and that the stronger the acidity was of the buffered solution, the shorter the equilibrium swelling time was of the hydrogels. Drug‐release experiments in vitro were carried out at 37°C (close to body temperature), at pH 1.4 (close to the pH of the stomach), and at pH 7.4 (close to the pH of the intestine). The release results indicated that the drug (chloramphenicol) was released more rapidly from the prepared hydrogel in a pH 1.4 buffered solution than in a pH 7.4 one, and this was consistent with the results predicted from the experiments of the swelling kinetics. Moreover, the drug‐release process was confirmed by scanning electron micrographs of the hydrogels embedded with chloramphenicol. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3602–3608, 2006     

β‐cyclodextrin/poly(vinyl alcohol) hydrogels containing phenylpropionic acid and naphthylamine: dual pH‐sensitive release

Hydrogel composed of β‐cyclodextrin (β‐CD) and poly(vinyl alcohol) was prepared in a strong alkaline condition using epichlorohydrin as a crosslinker. Phenylpropionic acid (PPA) and naphthylamine (NA) were loaded in the cavities of β‐CD residues to endow the hydrogel with a dual pH‐sensitive characteristic. In release experiments using fluorescein isothiocyanate‐dextran (FITC‐dextran) as a dye, PPA/NA‐loaded hydrogel exhibited an extensive release not only in acidic conditions (e.g. pH 3.0) but also in alkaline conditions (e.g. pH 9.0). PPA and NA will be highly ionized at the alkaline and the acidic pH and they could promote swelling of the hydrogel, causing an extensive release at those pH values. However, the release was suppressed at mid pH values (e.g. pH 5.0 and pH 7.4), possibly due to the formation of salt bridges between PPA^? and NA⁺. In fact, the degree of swelling at mid pH was lower than that observed at strong acidic pH and alkaline pH. According to SEM images, the pore size and the texture compactness of hydrogels which had been subjected to swelling at different pH values could also account for the dual pH‐sensitive releases. The hydrogels exhibited dual pH sensitivities in terms of FITC‐dextran release and swelling. These hydrogels might be used as a pH‐sensitive vehicle for water‐soluble drugs. © 2013 Society of Chemical Industry     

Synthesis,Characterization, and drug release study of acrylamide‐co‐itaconic acid based smart hydrogel

A new kind of pH and temperature responsive poly(acrylamide‐co‐itaconic acid) hydrogel was prepared by free radical polymerization using ammonium persulfate as initiator and different comonomer ratios. The hydrogels were characterized in terms of chemical composition, swelling‐deswelling behavior, morphology, crystallographic behavior, and drug release properties. All the hydrogels showed high swelling ability in aqueous solutions, the maximum being at pH 7. Swelling decreased on either side of pH 7 (i.e., both in acidic and alkaline region) and increased with increase in temperature. The hydrogel with 10 mol% itaconic acid (IA) absorbed maximum water among the copolymer gels. The cellular structures of the hydrogels were clearly revealed by microscopic analysis and SEM pictures. Swelling of the gels in water followed non‐Fickian type of diffusion principle. The hydrogel was proved to be a controlled release vehicle, for example in drug delivery by using its smart properties. The hydrogel with 10 mol% IA also absorbed maximum amount of drug (ascorbic acid) under study. Incorporation of drug in hydrogel matrix was established from XRD peak analysis. POLYM. ENG. SCI., 55:113–122, 2015. © 2014 Society of Plastics Engineers     

Synthesis and properties of degradable hydrogels of konjac glucomannan grafted acrylic acid for colon-specific drug delivery

In this paper, we reported the synthesis and properties of novel hydrogel systems designed for colon targeted drug delivery. The gels were composed of konjac glucomannan (KGM), copolymerized with acrylic acid (AA) and cross-linked by N,N-methylene-bis-(acrylamide) (MBAAm). The influence of various parameters on the equilibrium swelling ratios of the hydrogels was investigated. The swelling ratio was inversely proportional to the content of MBAAm. It was possible to modulate the degree of swelling of the gels by changing cross-linking density of the polymer. The gels' swelling ratio has sensitive respondence to the environmental pH value variation. The results of degradation test show that the hydrogels retain the enzymatic degradation character of KGM and they can be degraded for 52.5% in 5 days by Cellulase E0240. In vitro release of model drug 5-aminosalicylic acid (5-ASA) was studied in the presence of Cellulase E0240 in pH 7.4 phosphate buffer at 37 °C. The accumulative release percent of 5-ASA reached 95.19% after 36 h and the drug release was controlled by the swelling and degradation of the hydrogels.     

Carboxymethyl sago pulp/carboxymethyl sago starch hydrogel: Effect of polymer mixing ratio and study of controlled drug release

Carboxymethyl sag o pulp (CMSP)/carboxymethyl sago starch (CMSS) hydrogel was synthesized by electron beam irradiation. In the series of hydrogels prepared, 40%/20% CMSP/CMSS hydrogel had the highest gel fraction. The swelling capacity of CMSP/CMSS hydrogel was found to be highest in distilled water, followed by pH 11, pH 7.4, and pH 1.2. Scanning Electron Microscope photographs revealed that the drug‐loaded hydrogel had a smoother surface than unloaded hydrogel. Fourier Transform Infrared and Differential Scanning Calorimetry analysis showed the absence of interaction between the hydrogels and the drug. All drug‐loaded hydrogels had drug encapsulation efficiency between 63% and 69%. CMSP/CMSS hydrogel swelled and allowed the release of drug at pH 7.4. These properties qualify the hydrogel as a potential candidate for controlled drug release at the ocular and colonic regions. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43652.     

Influence of chain length of diol on the swelling behavior of citric acid based pH sensitive polymeric hydrogels: A green approach

Synthesis of pH‐sensitive hydrogels of citric acid with varying diol units viz., 1,2 Ethane diol, 1,4 butane diol, and 1,6 hexane diol along with methacrylic acid towards the solventless green approach. The formations of the hydrogels were identified using FTIR spectroscopy. Thermal characterization (thermo gravimetric analysis, differential thermal analysis (DTA), and differential scanning calorimetry) and morphology of the synthesized hydrogels have been investigated. Swelling studies of hydrogels in various pH ranging from 4.0 to 10.0 have been investigated. The results of the swelling studies implied that percentage of swelling comparatively higher at neutral pH (7.4) than at acidic and alkaline pH. The inverse relationship was noticed, where ascending the diol units of hydrogel in swelling equilibrium. The hydrogels with the increasing chain length show a noticeable pH sensitivity and which could be considered as smart hydrogel. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41403.     

Self‐healing hydrogel of poly(vinyl alcohol)/graphite oxide with pH‐sensitive and enhanced thermal properties

Supramolecular hydrogel is a fascinating polymeric material composed of three‐dimensional noncovalent networks with many outstanding properties, especially reversible relevant performances. A self‐healing supramolecular hydrogel of poly(vinyl alcohol)/graphite oxide, with reversible pH responsiveness and good thermal stability, was prepared. The morphology, functional group changes, swelling performance, thermal stability, rheological performance, and self‐healing property of the PVA/GO hydrogel were investigated. A probable mechanism between the components and potential applications were also examined in our study. The experimental results show that the PVA/GO hydrogel was not only self‐healable without external stimulus or addition of any healing agents, but also pH sensitive and with good thermal stability. Green ingredients (PVA and GO) and a simple synthesis method (a freezing/thawing treatment) may pose little threat to the environment and also promote the production of such hydrogels. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46143.     

Preparation and application in drug controlled delivery of pH‐sensitive P(CE‐co‐DMAEMA‐co‐MEG) hydrogel

A pH‐sensitive hydrogel [P(CE‐co‐DMAEMA‐co‐MEG)] was synthesized by the free‐radical crosslinking polymerization of N,N‐dimethylaminoethyl methacrylate (DMAEMA), poly(ethylene glycol) methyl ether methacrylate(MPEG‐Mac) and methoxyl poly(ethylene glycol)‐poly(caprolactone)‐methacryloyl methchloride (PCE‐Mac). The effects of pH and monomer content on swelling property, swelling and deswelling kinetics of the hydrogels were examined and hydrogel microstructures were investigated by SEM. Sodium salicylate was chosen as a model drug and the controlled‐release properties of hydrogels were pilot studied. The results indicated that the swelling ratios of the gels in stimulated gastric fluids (SGF, pH = 1.4) were higher than those in stimulated intestinal fluids (SIF, pH = 7.4), and followed a non‐Fickian and a Fickian diffusion mechanism, respectively. In vitro release studies showed that its release rate depends on different swelling of the network as a function of the environmental pH and DMAEMA content. SEM micrographs showed homogenous pore structure of the hydrogel with open pores at pH 1.4. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40737.     

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‐ and temperature‐responsive IPN hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate)

pH‐ and temperature‐responsive interpenetrating polymer network (IPN) hydrogels based on soy protein and poly(N‐isopropylacrylamide‐co‐sodium acrylate) were successfully prepared. The structure and properties of the hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry, and thermogravimetric analyzer. The equilibrium and dynamic swelling/deswelling behaviors and the drug release properties of the hydrogels responding to pH and/or temperature were also studied in detail. The hydrogels have the porous honeycomb structures, good miscibility and thermal stability, and good pH‐ and temperature‐responsivity. The volume phase transition temperature of the hydrogels is ca. 40°C. Changing the soy protein or crosslinker content could be used to control the swelling behavior and water retention, and the hydrogels have the fastest deswelling rate in pH 1.2 buffer solutions at 45°C. Bovine serum albumin release from the hydrogels has the good pH and temperature dependence. The results show that the proposed IPN hydrogels may have potential applications in the field of biomedical materials such as in drug delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39781.     

Dual‐responsive semi‐interpenetrating network beads based on calcium alginate/poly(N‐isopropylacrylamide)/poly(sodium acrylate) for sustained drug release

To improve the mechanical strength of natural hydrogels and to obtain a sustained drug‐delivery device, temperature‐/pH‐sensitive hydrogel beads composed of calcium alginate (Ca‐alginate) and poly(N‐isopropylacrylamide) (PNIPAAm) were prepared in the presence of poly(sodium acrylate) (PAANa) with ultrahigh molecular weight (M_η ≥ 1.0 × 10⁷) as a strengthening agent. The influence of PAANa content on the properties, including the beads stability, swelling, and drug‐release behaviors, of the hydrogels was evaluated. Scanning electron microscopy and oscillation experiments were used to analyze the structure and mechanical stability of the hydrogel beads, respectively. The results show that stability of the obtained Ca‐alginate/PNIPAAm hydrogel beads strengthened by PAANa the alginate/poly(N‐isopropyl acrylamide) hydrogel bead (SANBs) was significantly improved compared to that of the beads without PAANa (NANBs) at pH 7.4. The swelling behavior and drug‐release capability of the SANBs were markedly dependent on the PAANa content and on the environmental temperature and pH. The bead sample with a higher percentage of PAANa exhibited a lower swelling rate and slower drug release. The drug release profiles from SANBs were further studied in simulated intestinal fluid, and the results demonstrated here suggest that SANBs could serve as a potential candidate for controlled drug delivery in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Synthesis and characterization of novel pH‐sensitive chitosan‐poly(acrylamide‐co‐itaconic acid) hydrogels

Novel pH‐sensitive chitosan‐poly(acrylamide‐co‐itaconic acid) hydrogels were prepared by free radical copolymerization of acrylamide and itaconic acid (IA) in chitosan solution. The hydrogels were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, differential scanning calorimetry and the swelling ratios of the hydrogels in water (pH 6.8) and pH 1.2. The influence of composition on the thermal properties of the hydrogels was assessed. The glass transition temperatures of the samples increased with IA content, ranging from 110 to 136 °C. Swelling of the hydrogels was found to obey second‐order kinetics with respect to the remnant swelling, indicating that diffusion is controlled by the relaxation of chains. The equilibrium swelling degree was strongly dependent on pH and composition. At both pH values the highest water uptake was obtained for the IA‐free sample M1. From the equilibrium swelling results the average molar mass between crosslinks, M_c, and the crosslink density of the chitosan‐poly(acrylamide‐co‐itaconic acid) samples were calculated. The results evidenced the reinforcing effect of IA on the hydrogel structure. It is concluded that these highly swellable pH‐sensitive hydrogels can be useful for applications in biomedicine and pharmacy. © 2013 Society of Chemical Industry     

Sustained release of potassium diclofenac from a pH‐responsive hydrogel based on gum arabic conjugates into simulated intestinal fluid

This work describes the preparation, the swelling properties and the potassium diclofenac (KDF) release profile of hydrogels of gum arabic (GA), N′,N′‐dimethylacrylamide, and methacrylic acid. In order to convert GA into a hydrogel, the polysaccharide was vinyl‐modified with glycidyl methacrylate. The hydrogels showed pH‐responsive swelling changes, which were more expressive in the basic environment. Release data of KDF were adjusted to a diffusion‐based kinetic model that provides an important insight on affinity of the drug for hydrogel and solvent, which may be the leading parameter for release of guest molecules from polymers. The KDF release from the hydrogels into simulated intestinal fluid decreases when the amount of modified GA increases. This was demonstrated to be due to the higher affinity of KDF for GA‐richer hydrogel, which makes the anti‐inflammatory release less favorable. The analysis of released drug half‐time (t_1/2 = 16.10 and 21.51 h) indicated sustained release characteristics. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43319.     

Chitosan/poly(vinyl alcohol) hydrogels for amoxicillin release

Chitosan and poly(vinyl alcohol)-based hydrogel films were synthesized using tartaric acid as a crosslinking agent. The films denoted as CVT were then characterized using Fourier transform infrared, Nuclear magnetic resonance, X-ray diffraction, and scanning electron microscopy analysis. TG/DTG and DSC analysis were also carried out for the determination of thermal properties of hydrogel films. Swelling properties of these hydrogel films were investigated at two different pHs and temperatures. The swelling behaviors of all samples were increased in acidic medium, while decreased in alkaline medium. The enzymatic degradation of the hydrogels was studied using lysozyme, and degradation rates were found to be parallel with the swelling ratio for CVT hydrogel. The hydrogels were also used for the amoxicillin release in KCl/HCl and PBS buffer solutions. The release behaviors of CVT hydrogel films were slower and can be controlled as compared with commercial drug release systems. CVT hydrogel films may be more appropriate for controlled release of amoxicillin.     

Thermoreversible hydrogels X: Synthesis and swelling behavior of the (N‐isopropylacrylamide‐co‐sodium 2‐acrylamido‐2‐methylpropyl sulfonate) copolymeric hydrogels

A series of thermosensitive hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm) and sodium‐2‐acrylamido‐2‐methylpropyl sulfonate (NaAMPS). Factors such as temperature and initial total monomer concentration and different pH solutions were investigated. Results indicated that the more the NaAMPS content in hydrogel system, the higher the swelling ratio and the gel transition temperature; the higher the initial monomer concentration, the lower the swelling ratio. The result also indicated that the NIPAAm/NaAMPS copolymeric hydrogels had different swelling ratios in various pH environments. The present gels showed a pH‐reversible property between pH 3 and pH 10 and thermoreversibility. The swelling ratios of copolymeric gels were lower in a strong alkaline environment because the gels were screened by counterions. Finally, the drug release behavior of these gels was also investigated in this article. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1760–1768, 2000     

Dual pH‐ and temperature‐responsive hydrogels with extraordinary swelling/deswelling behavior and enhanced mechanical performances

pH‐ and temperature‐responsive semi‐interpenetrating nanocomposite hydrogels (NC hydrogels) were prepared with surface‐functionalized graphene oxide (GO) as the crosslinker, N‐isopropylacrylamide (NIPAM) as the monomer, and chitosan (CS) as an additive. The effects of 3‐(trimethoxysilyl)propylmethacrylate‐modified GO sheets and CS content on various physical properties were investigated. Results show that PNIPAM/CS/GO hydrogels undergo a large volumetric change in response to temperature. Swelling ratios of PNIPAM/CS/GO hydrogels are much larger than those of the conventional organically crosslinked PNIPAM hydrogels. The deswelling test indicates that the deswelling rate was greatly enhanced by incorporating CS into the hydrogel network and using the surface‐functionalized GO as the crosslinker. The pH‐sensitivity of PNIPAM/CS/GO hydrogels is evident below their volume phase transition temperature. Moreover, the PNIPAM/CS/GO hydrogels have a much better mechanical property compared with traditional hydrogels even in a high water content of 90%. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41530.     

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.