Preparation and in vitro evaluation of new pH‐sensitive hydrogel beads for oral delivery of protein drugs

New biodegradable pH‐responsive hydrogel beads based on chemically modified chitosan and sodium alginate were prepared and characterized for the controlled release study of protein drugs in the small intestine. The ionotropic gelation reaction was carried out under mild aqueous conditions, which should be appropriate for the retention of the biological activity of an uploaded protein drug. The equilibrium swelling studies were carried out for the hydrogel beads at 37°C in simulated gastric (SGF) and simulated intestinal (SIF) fluids. Bovine serum albumin (BSA), a model for protein drugs was entrapped in the hydrogels and the in vitro drug release profiles were established at 37°C in SGF and SIF. The preliminary investigation of the hydrogel beads prepared in this study showed high entrapment efficiency (up to 97%) and promising release profiles of BSA. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Poly(methacrylamide‐co‐acrylic acid) hydrogels for gastrointestinal delivery of theophylline. I. Swelling characterization

pH sensitive copolymeric hydrogels have been synthesized by free‐radical polymerization of methacrylamide and acrylic acid in aqueous medium. The gels were characterized by FTIR spectroscopy, thermogravimetric analysis, and swelling measurements. To determine the suitability of theses hydrogels for gastrointestinal oral delivery of model drug theophylline, their swelling behavior was investigated as a function of pH and various structural parameters such as the average molecular weight between crosslinks, crosslink density, and mesh size were calculated. Likewise initial, average and late time diffusion coefficients were also evaluated in simulating intestinal fluid of pH 6.8 at 37°C. The gel underwent sharp volume phase transition in the vicinity of pH 5.8. The mesh sizes of the hydrogel were between 8.4 and 9.2 Å in the collapsed state (pH range 1–2; SGF) and between 514 and 524 Å in the swollen state (pH range 7–8; SIF). The experimental data was found to fit well to Beren‐Hopfenberg equation thus suggesting that later part of swelling was chain relaxation controlled. The activation energy, as determined from Arrhenius equation was found to be 13.71 kJ mol^?1. Likewise, enthalpy of mixing was also evaluated using Gibbs‐Helmholtz equation. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 2995–3008, 2006     

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响应性P(AA-co-C8PhEO10Mac) 水凝胶的制备及其对L-抗坏血酸的控释性能

采用自由基交联共聚法合成了具有pH敏感性的水凝胶聚丙烯酸-co-甲基丙烯酸辛基酚聚氧乙烯醚酯〔P(AA-co-C8PhEO10Mac)〕,考察了不同单体配比的水凝胶在不同pH的缓冲溶液中的溶胀性、溶胀动力学和退溶胀动力学。通过浸泡法在水凝胶中载入L-抗坏血酸,初步研究了模拟胃肠液中,凝胶对L-抗坏血酸的释放行为。结果表明,凝胶兼具快速的溶胀和退溶胀速率,良好的pH敏感性等特征;载药凝胶在模拟肠液(SIF,pH=7.4)中对药物的累计释放率明显大于在模拟胃液(SGF,pH=1.4)中的累计释放率,增大丙烯酸的用量使累计释放率先升高后降低。采用滤纸片法研究了甲基丙烯酸辛基酚聚氧乙烯醚酯(C8PhEO10Mac)对大肠杆菌、酿酒酵母的抑制作用,结果显示,在10～50 mmol/L的测试浓度水平,C8PhEO10Mac对二者均无明显的抑制作用。     

Synthesis of copolymeric acrylamide/potassium acrylate hydrogels blended with poly(vinyl alcohol): Effect of crosslinking and the amount of poly(vinyl alcohol) on swelling behavior

A novel series of copolymeric acrylamide/potassium acrylate superabsorbents, blended with poly(vinyl alcohol), have been synthesized by using N, N′‐methylenebisacrylamide as a crosslinker and potassium persulphate (K₂S₂O₈) as an initiator. Swelling behavior of these hydrogels in water was investigated; and on the basis of swelling properties, the diffusional behavior of water into these hydrogel systems was analyzed. It was observed that with the increase of amount of poly(vinyl alcohol) or crosslinking, the swelling of the hydrogels decreased. The hydrogel synthesized by addition of 5% poly(vinyl alcohol) and 0.25% crosslinking showed maximum swelling of 54445%. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1927–1931, 2005     

Preparation of novel pH‐sensitive nanocomposites based on ionic‐liquid modified montmorillonite for colon specific drug delivery system

An ionic liquid monomer, 3‐methyl‐1‐[2‐(2‐methyl‐acryloxy)‐ethyl]‐imidazolium chloride, was synthesized through the quaternization of N‐methylimidazole and 2‐chloroethyl methacrylate. This ionic liquid monomer intercalated into the montmorillonite layers and subsequently copolymerized with methacrylic acid. The organic–inorganic composite was characterized by FTIR, XRD, SEM, and EDX to study their structure and properties. Naproxen as a model drug was entrapped in these pH‐sensitive positively charged nano carriers and the in vitro release profiles were established separately in both enzyme‐free simulated gastric and intestinal fluids (SGF, pH 1) and (SIF, pH 7.4) respectively. It was observed that the drug release percentages in SIF were higher; hence the prepared nanocomposite could be considered as a suitable carrier for colon specific drug delivery. POLYM. COMPOS., 182–187, 2016. © 2014 Society of Plastics Engineers     

pH‐thermoreversible hydrogels. I. Synthesis and swelling behaviors of the (N‐isopropylacrylamide‐co‐acrylamide‐co‐2‐hydroxyethyl methacrylate) copolymeric hydrogels

A series of pH‐thermoreversible hydrogels that exhibited volume phase transition was synthesized by various molar ratios of N‐isopropylacrylamide (NIPAAm), acrylamide (AAm), and 2‐hydroxyethyl methacrylate (HEMA). The influence of environmental conditions such as temperature and pH value on the swelling behavior of these copolymeric gels was investigated. Results showed that the hydrogels exhibited different equilibrium swelling ratios in different pH solutions. Amide groups could be hydrolyzed to form negatively charged carboxylate ion groups in their hydrophilic polymeric network in response to an external pH variation. The pH sensitivities of these gels also depended on the AAm content in the copolymeric gels; thus the greater the AAm content, the higher the pH sensitivity. These hydrogels, based on a temperature‐sensitive hydrogel, demonstrated a significant change of equilibrium swelling in aqueous media between a highly solvated, swollen gel state and a dehydrated network response to small variations of temperature. pH‐thermoreversible hydrogels were used for a study of the release of a model drug, caffeine, with changes in temperature. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 221–231, 1999     

Thermoreversible hydrogel. XVII. Investigation of the drug release behavior for [N‐isopropylacrylamide‐co‐trimethyl acrylamidopropyl ammonium iodide‐co‐3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate] copolymeric hydrogels

A series of copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm), trimethyl acrylamidopropyl ammonium iodide (TMAAI), and 3‐dimethyl (methacryloyloxyethyl) ammonium propane sulfonate (DMAPS). Results showed that the swelling ratios of these copolymeric hydrogels increased with an increase of TMAAI content. The drug release behavior of the ionic thermosensitive hydrogels related to their ionicity and drug types. Results indicated that the release ratio of caffeine in the hydrogels was not affected by the ionicity of hydrogels, but increased with increasing of the swelling ratio. The anionic solute (phenol red) strongly interacted with cationic hydrogel (very large K_d), so the phenol red release ratio in cationic gels was very low. On the other hand, CV was adsorbed only on the skin layer of the cationic hydrogel because of the charge repulsion, and released rapidly. Therefore the release ratio was highest for cationic hydrogel to cationic drug. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1592–1598, 2002     

Synthesis and Characterization of Polymer/Silica Composite for Colon-Specific Drug Delivery

The free-radical graft polymerization of hydrophobic glycomonomer onto surface-activated perlite particles was studied experimentally. The grafting procedure consisted of surface activation with 3-(trimethoxysilyl) propyl methacrylate (TSPA), followed by free-radical graft polymerization of glucose acrylate (GA), using persulfate as an initiator. pH-Sensitive hydrogel synthesis was carried out by carboxymethylation mixing composite with sodium monochloroacetate (SMCA). Insulin was entrapped in these gels and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4).     

Synthesis and swelling behavior of thermosensitive IPN hydrogels based on sodium acrylate and N‐isopropyl acrylamide by a two‐step method

A series of interpenetrating polymer network (IPN) hydrogels having higher swelling ratio (SR) and thermosensitivity were synthesized from sodium acrylate (SA) and N‐isopropyl acrylamide (NIPAAm) by a two‐step method. A series of the porous poly(sodium acrylate ‐co‐1‐vinyl–2‐pyrrolidone) [poly(SA‐co‐VP)], (SV), hydrogels were prepared from acrylic acid having 90% degree of neutralization and VP monomer in the first step. The second step is to immerse the SV dried gels into the NIPAAm solution containing initiator, accelerator, and crosslinker to absorb NIPAAm solution and then polymerized to form the poly(SA‐co‐VP)/poly(NIPAAm) IPN hydrogels (SVN). The effect of the different molar ratios of SA/VP and the content of NIPAAm on the swelling behavior and physical properties of the SVN hydrogels was investigated. Results showed that the SVN hydrogels displayed an obviously thermoreversible behavior when the temperature turns across the critical gel transition temperature (CGTT) of poly(NIPAAm) hydrogel. The pore diameter distributions inside the hydrogel also indicated that the pore sizes inside the SVN hydrogels were smaller than those inside the SV hydrogels. At the same time, the more proportion of SA was added into the hydrogel, the larger pore diameter of the SV hydrogel was formed. The results also showed that the SR decreased with an increase of the VP content in the SV hydrogel and more obviously decreased in the SVN hydrogels. The SVN networks also showed stronger shear moduli than SV hydrogels. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

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     

Modulating properties of chemically crosslinked PEG hydrogels via physical entrapment of silk fibroin

A variety of polymers of synthetic origins (e.g., poly(ethylene glycol) or PEG) and macromolecules derived from natural resources (e.g., silk fibroin or SF) have been explored as the backbone materials for hydrogel crosslinking. Purely synthetic PEG‐based hydrogels are often chemically crosslinked to possess limited degradability, unless labile motifs are designed and integrated into the otherwise non‐degradable macromers. On the other hand, SF produced by Bombyx mori silkworm can be easily formulated into physical hydrogels. These physical gels, however, are less stable than the chemically crosslinked gels. Here, we present a simple strategy to prepare hybrid PEG‐SF hydrogels with chemically crosslinked PEG network and physically entrapped SF. Visible light irradiation initiated rapid thiol‐acrylate gelation to produce a network composed of non‐degradable poly(acrylate‐co‐NVP) chains, hydrolytically labile thioether ester bonds, and interpenetrating SF fibrils. We evaluated the effect of SF entrapment on the crosslinking efficiency and hydrolytic degradation of thiol‐acrylate PEG hydrogels. We further examined the effect of adding soluble SF or sonicated SF (S‐SF) on physical gelation of the hybrid materials. The impacts of SF or S‐SF inclusion on the properties of chemically crosslinked hybrid hydrogels were also studied, including gel points, gel fraction, equilibrium swelling ratio, and mesh size. We also quantified the fraction of SF retention in PEG hydrogels, as well as the influence of remaining SF on moduli and degradation of chemically crosslinked thiol‐acrylate PEG hydrogels. This simple hybrid hydrogel fabrication strategy should be highly useful in future drug delivery and tissue engineering applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43075.     

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     

Thermoreversible hydrogels. XIX. Synthesis and swelling behavior and drug release behavior for the N‐isopropylacrylamide/poly(ethylene glycol) methylether acrylate copolymeric hydrogels

A series of thermosensitive copolymeric hydrogels were prepared from various molar ratios of N‐isopropylacrylamide (NIPAAm) and poly(ethylene glycol) methylether acrylate (PEGMEA_n), which was synthesized from acryloyl chloride and poly(ethylene glycol) mono methylether with three oxyethylene chain lengths. Investigation of the effect of the chain length of oxyethylene in PEGMEA_n, and the amount of the PEGMEA_n in the NIPAAm/PEGMEA_n copolymeric gels, on swelling behavior in deionized water was the main purpose of this study. Results showed that the swelling ratio for the present copolymeric gels increased with increasing chain length of oxyethylene in PEGMEA_n and also increased with increase in the amount of PEGMEA_n in the copolymeric gels. However, the gel strength and effective crosslinking density of these gels decreased with increase in swelling ratio. Some kinetic parameters were also evaluated in this study. Finally, the drug release and drug delivery behavior for these gels were also assessed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1683–1691, 2003     

Adsorption of surfactant by hydrophobically modified poly[2‐(diethylamino)ethylmethacrylate‐co‐N‐vinyl‐2‐pyrrolidone/octadecyl acrylate)] hydrogels and effect of surfactant adsorption on the volume phase transition

Hydrophobically modified poly[2‐(diethylamino)ethylmethacrylate‐co‐N‐vinyl‐2‐pyrrolidone/octadecyl acrylate) [P(DEAEMA‐co‐NVP/OA)] hydrogels were synthesized by free‐radical crosslinking copolymerization of 2‐(diethylamino)ethylmethacrylate (DEAEMA), N‐vinyl‐2‐pyrrolidone (NVP) with different amounts of hydrophobic comonomer octadecyl acrylate (OA) in tert‐butanol with ethylene glycole dimethacrylate (EGDMA) as a crosslinker. The swelling equilibrium of the hydrogels was investigated as a function of temperature and hydrophobic comonomer content in aqueous solutions of the anionic surfactant sodium dodecyl sulfate (SDS) and the cationic surfactant dodecyltrimethylammonium bromide (DTAB). The results indicated that the swelling behavior and temperature sensitivity of the hydrogels were affected by the type and concentration of surfactant solutions. Additionally, the amount of the adsorbed SDS and DTAB molecules onto the hydrogels was determined by fluorescence measurements. An increase of OA content in the hydrogel caused an increase in the amount of adsorbed surfactant molecules in both media. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3771–3775, 2007     

Synthesis and swelling properties of 2‐hydroxyethyl methacrylate‐co‐1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine hydrogels

A series of 2‐hydroxyethyl methacrylate/1‐vinyl‐3‐(3‐sulfopropyl)imidazolium betaine (HEMA/VSIB) copolymeric gels were prepared from various molar ratios of HEMA and the zwitterionic monomer VSIB. The influence of the amount of VSIB in copolymeric gels on their swelling behavior in water and various saline solutions at different temperatures and the drug‐release behavior, compression strength, and crosslinking density were investigated. Experimental results indicated that the PHEMA hydrogel and the lower VSIB content (3%) in the HEMA/VSIB gel exhibited an overshooting phenomenon in their dynamic swelling behavior, and the overshooting ratio decreased with increase of the temperature. In the equilibrium water content, the value increased with increase of the VSIB content in HEMA/VSIB hydrogels. In the saline solution, the water content for these gels was not affected by the ion concentration when the salt concentration was lower than the minimum salt concentration (MSC) of poly(VSIB). When the salt concentration was higher than the MSC of poly(VSIB), the deswelling behavior of the copolymeric gel was more effectively suppressed as more VSIB was added to the copolymeric gels. However, the swelling behavior of gels in KI, KBr, NaClO₄, and NaNO₃ solutions at a higher concentration would cause an antipolyelectrolyte phenomenon. Besides, the anion effects were larger than were the cation effects in the presence of a common anion (Cl^?) with different cations and a common cation (K⁺) with different anions for the hydrogel. In drug‐release behavior, the addition of VSIB increased the drug‐release ratio and the release rate. Finally, the addition of VSIB in the hydrogel improved the gel strength and crosslinking density of the gel. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 2888–2900, 2001     

Chitosan‐based interpolymeric pH‐responsive hydrogels for in vitro drug release

Two series of pH‐responsive biodegradable interpolymeric (IPN) hydrogels based on chitosan (Ch) and poly(vinyl alcohol) (PVA) were prepared for controlled drug release investigations. The first series was chemically crosslinked with different concentrations of glutaraldehyde and the second was crosslinked upon γ‐irradiation by different doses. The equilibrium swelling characteristics were investigated for the gels at 37°C in buffer solutions of pH 2.1 and 7.4 as simulated gastric and intestinal fluids, respectively. 5‐Fluorouracil (FU) was entrapped in the hydrogels, as a model therapeutic agent, and the in vitro release profiles of the drug were established at 37°C in pH 2.1 and 7.4. FTIR, SEM, and X‐ray diffraction analyses were used to characterize and investigate the structural changes of the gels with the variation of the blend composition and crosslinker content before and after the drug loading. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2864–2874, 2007     

Preparation and characterization of dual responsive sodium alginate‐g‐poly(vinyl alcohol) hydrogel

Poly(vinyl alcohol) (PVA) was chosen as a controllable gelator to prepare sodium alginate (SA)‐based physically cross‐linked dual‐responsive hydrogel by three steps. First, polyvinyl acetate (PVAc) was grafted onto SA via radical copolymerization. Then, the copolymer was subsequently converted into SA‐g‐poly(vinyl alcohol) (SAPVA) by alcoholysis reaction. PVA content of SAPVA was tailored by controlling the graft percentage of PVAc, i.e. through varying the amount of vinyl acetate during copolymerization. Finally, SAPVA hydrogels were formed by freezing‐thawing cycles. The structure of the graft copolymers was verified with FTIR spectroscopy. X‐ray diffraction analysis results revealed that the crystallinity of SAPVA hydrogels depended on the PVA content of SAPVA. The swelling test showed that SAPVA hydrogels were pH‐responsive, and the swelling was reversible. SAPVA hydrogels also behaved electric‐responsive. In addition, the pH‐sensitivity of SAPVA hydrogels was able to be controlled with the composition of the hydrogels. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Thermoreversible hydrogels. IX. Swelling behaviors of thermosensitive hydrogels copolymerized by N‐isopropylacrylamide with 1‐vinyl‐3‐(3‐sulfopropyl) imidazolium betaine

A series of thermosensitive hydrogels were prepared from the various molar ratios of N‐isopropylacrylamide, 1‐vinyl‐3‐(3‐sulfopropyl) imidazolium betaine (VSIB), and N,N′‐methylene‐bis‐acrylamide. The influence of the amount of VSIB in the copolymeric gels on the swelling behaviors in water, in various saline solutions, and at various temperatures was investigated. The results indicated that the higher the VSIB content in the hydrogel system, the higher the swelling ratio and the gel transition temperature. In the saline solution the results showed that when the concentration of salt is higher than the minimum salt concentration (MSC) of poly(VSIB), the deswelling behavior of the copolymeric gel was more effectively suppressed as more VSIB was added to the copolymeric gels. In addition, only the sample containing 12 mol % VSIB (V4) exhibited an antipolyelectrolyte's swelling behavior when the concentration of salt was higher than the MSC of poly(VSIB). This means that the swelling ratio of the hydrogel can be improved with a higher concentration salt solution. In addition, the anion effects were larger than the cation effects in the presence of a common anion (Cl⁻) with different cations and a common cation (K⁺) with different anions for the hydrogel. Finally, the more VSIB in the hydrogel, the higher the diffusion coefficient in dynamic swelling. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 14–23, 2000     

Thermoreversible hydrogels. XV. Swelling behaviors and drug release for thermoreversible hydrogels containing silane monomers

Three series of thermosensitive copolymeric hydrogels were prepared from [3‐(methacryloyloxy)propyl]trimethoxysilane (MPTMOS), [2‐(methacryloyloxy)ethoxy]trimethylsilane (METMS), and (methacryloyloxy)trimethylsilane (MTMS), referred to as the silane monomer, and N‐isopropylacrylamide (NIPAAm) by solution polymerization. The influence of the structures and amounts of silane monomers on the swelling and drug‐released behaviors were studied. The results showed that, because of the hydrophobicity of the silyl group, the more silane monomers in the copolymeric hydrogels the lower was the swelling ratio of the gels. The hydrophobicity of the silyl group affected the swelling mechanism, which resulted from the non‐Fickian diffusion for the gels. The copolymeric gels clearly exhibited gel transition temperatures. The copolymeric hydrogels could be applied to a drug‐release and drug‐delivery system. The delivery amount would approach a steady state after three cycle operations of delivery. The gels also showed an on–off switch behavior on drug release depending on the temperature, and the gels released more CV with the gels in a swollen state. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 2523–2532, 2002