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     

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     

Preparation and characterization of pH‐sensitive hydrogels based on chitosan,itaconic acid and methacrylic acid

Novel pH‐sensitive hydrogels based on chitosan, itaconic acid and methacrylic acid were prepared in two steps. Chitosan was first ionically crosslinked with itaconic acid, after which a free radical polymerization and crosslinking of the chitosan/itaconic acid network was performed by adding methacrylic acid and a crosslinker in order to achieve better mechanical properties and tunable swelling. The samples were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, X‐ray diffraction, dynamic mechanical analysis and the swelling ratios of the hydrogels at various pH values (2.0–8.0). The hydrogel composition is found to have a great impact on the hydrogel structure, mechanical and thermal properties, morphology and swelling kinetics. The highly porous morphology of the gels is probably connected with the bulky chitosan/itaconic acid network which reduces the degree of crosslinking in the second step of the synthesis due to steric hindrances. The gels demonstrate substantial change in buffer absorbency with change of pH, low for acid buffers and the higher for pH values above 6 where the swelling is considerably slow, thus suggesting their strong candidature for use as oral drug‐delivery systems in the lower parts of the gastrointestinal tract and for drugs that require longer release times. Copyright © 2010 Society of Chemical Industry     

Controlled release of aminophylline from poly (N‐isopropylacrylamide‐co‐itaconic acid) hydrogels

N‐Isopropylacrylamide (NIPA) has been copolymerized with itaconic acid (IA) in the presence of N,N‐methylenebisacrylamide (BIS) as crosslinker. The swelling capacity and the release rate of aminophylline at 37 °C are reported. Maximum equilibrium swelling increases as the itaconic acid content in the hydrogel increases. The experimental data suggest clearly that the swelling process obeys second‐order kinetics. According to this, the kinetic constant, k, and the maximum equilibrium swelling, W_∞, have been calculated. Drug release from fully swollen hydrogels follows Fick's law closely, but deviates from it for xerogels. © 2001 Society of Chemical Industry     

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     

Swelling behaviors of ionic poly(N,N‐dimethylacrylamide‐co‐acrylamide) hydrogels in various media

Polyelectrolyte hydrogels were synthesized from N,N‐dimethylacrylamide, acrylamide, and itaconic acid with ammonium persulfate as a free‐radical initiator in the presence of methylene(bis)acrylamide as a crosslinker. The swelling behavior of the ionic poly(N,N‐dimethylacrylamide‐co‐acrylamide) hydrogels was investigated in pure water, in KSCN solutions with pHs 4 and 9, and in water–acetone mixtures according to the itaconic acid content in the hydrogel. The pulsatile swelling behavior of these hydrogels was studied both in water–acetone and in pH 2–9 buffer solutions. Although the equilibrium swelling ratio of the hydrogels with low concentrations of itaconic acid was almost not affected by changes in the temperature, the equilibrium swelling ratio of the hydrogels with high concentrations of itaconic acid increased in the temperature range of 20–50°C. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 2140–2145, 2007     

Determination of swelling behavior and morphological properties of poly(acrylamide‐co‐itaconic acid) and poly(acrylic acid‐co‐itaconic acid) copolymeric hydrogels

Poly(acrylamide‐co‐itaconic acid) (PAAmIA) and poly(acrylic acid‐co‐itaconic acid) (PAAIA) copolymeric hydrogels were prepared with different compositions via free‐radical polymerization. Ethylene glycol dimethacrylate (EGDMA) was used as an original crosslinker for these monomers. Gelation percentages of the monomers were studied in detail and it was found that addition of IA into the monomer mixture decreased the gelation percentage. The variation in swelling values (%) with time, temperature, and pH was determined for all hydrogels. PAA, which is the most swollen hydrogel, has the swelling percentage value of 2000% at pH = 7.4, 37°C. Swelling behaviors were explained with detailed SEM micrographs, which show the morphologic differences between dry and swollen hydrogels. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 5994–5999, 2006     

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     

Dynamic and equilibrium swelling studies: crosslinked pH sensitive methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels

In the present work crosslinked methyl methacrylate-co-itaconic acid (MMA-co-IA) hydrogels were prepared by free radical copolymerization of methyl methacrylate (MMA) with itaconic acid (IA) using ethylene glycol dimethacrylate (EGDMA) and N, N methylene bisacrylamide (MBAAm) as crosslinkers and benzoyl peroxide as initiator. Prepared hydrogels were investigated for dynamic and equilibrium swelling studies. For swelling behaviour, effect of pH, monomeric compositions, degree of crosslinking and type of crosslinking agent were investigated. Swelling studies were performed in the USP phosphate buffer solutions of varying pH 1.2, 4.5, 5.5, 6.5 and 7.0. Results showed that swelling increased by increasing IA content in hydrogels structure. This may be due to the presence of more carboxylic groups available for ionization. Swelling was decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Hydrogels were characterized by Fourier transform infrared (FTIR), and scanning electron microscope (SEM). Polymer-solvent interaction parameters (χ) of hydrogels were determined by using Flory–Rehner theory of equilibrium swelling values. The analysis of diffusion mechanism from gels using Peppas model showed that all monomeric compositions and degrees of crosslinking followed Fickian diffusion.     

Environmentally sensitive hydrogels: N‐isopropyl acrylamide/Acrylamide/ Mono‐, Di‐, Tricarboxylic acid crosslinked polymers

Environmentally sensitive hydrogels responsive to various stimuli such as temperature, pH, ionic strength of the medium and the solvent were prepared by using N‐isopropyl acrylamide (NIPAM), acrylamide (AAm) and monomers that have various number of carboxylic acid (XA) functionality using N,N′‐methylene bisacrylamide (Bis) as crosslinker. Hydrogels were prepared via free radical polymerization reaction in aqueous solution. P(NIPAAm‐co‐AAm) and p(NIPAAm‐co‐AAm)/XA hydrogels that contain monoprotic crotonic acid (CA) exhibit a lover critical solution temperature (LCST) at 28°C, whereas p(NIPAAm‐co‐AAm)/IA (IA:itaconic acid), and P(NIPAAm‐co‐AAm)/ACA (ACA:acotonic acid) hydrogels exhibit a lover critical solution temperature at 30.7°C and 34.4°C, respectively. Spectroscopic and thermal analyses were performed for the structural and thermal characterizations of the prepared hydrogel. The swelling experiments as equilibrium swelling percentages by gravimetrically were carried out in different solvents, at different solutions temperature, pH, and ionic strengths to determine their effects on swelling characteristic of hydrogels. POLYM. ENG. SCI., 55:843–851, 2015. © 2014 Society of Plastics Engineers     

Swelling and drug release profile of poly(2‐ethyl‐2‐oxazoline)‐based hydrogels prepared by gamma radiation‐induced copolymerization

Poly(2‐ethyl‐2‐oxazoline) and acrylic acid were copolymerized in different compositions using γ‐rays‐induced polymerization and cross‐linking to obtain a series of pH‐sensitive hydrogels. The preparation parameters that may affect the copolymerization process such as the feed solution composition and irradiation dose were optimized. Swelling characteristics of the obtained polymeric hydrogels were evaluated. The results show the significant effects of the hydrogel composition, soaking time, and pH on the swelling equilibrium. The diffusion parameters obtained at pH 1 and 7 show the possibility of using the prepared hydrogels in the field of colon‐specific drug delivery systems. Ibuprofen as a model drug was loaded into (poly(2‐ethyl‐2‐oxazoline)/acrylic acid) copolymer hydrogel to investigate their drug release behavior at different pH values. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Kinetic degradation and controlled drug delivery system studies for sensitive hydrogels prepared by gamma irradiation

Ternary mixtures of N‐vinyl‐2‐pyrrolidone/itaconic acid and gelatin were irradiated by gamma rays at 30 kGy/s and at ambient temperature to prepared poly (NVP/IA and G) hydrogels. Poly (NVP/IA) hydrogels were prepared in different compositions (NVP/IA) mole ratio, (100/0), (98/1.5), (96.5/3.5), and (93/7.0) at 30 kGy. Then adding gelatin at different content (5, 10, 15, 20) mg to the best composition (NVP/IA/H₂O) (93/7)% for the characterization of network structure of these hydrogels, kinetic swelling drug release behavior and Scan Electron Microscope was studied. The equilibrium degree of swelling for P(NVP/IA) and P(NVP/IA/G) copolymer and the swelling‐degradation kinetics were also studies. According to dynamic swelling studies, both the diffusion exponent and the diffusion coefficient increase with increasing content of (IA), whereas, the addition of gelatin to (NVP/IA) composition by different content did not lead to any significant change in swelling percent. Also, the swelling behavior of copolymer hydrogels in response to pH value of the external media was studied, it is noted that the highest swelling values were at pH 4. The in vitro drug release behavior of these hydrogels was examined by quantification analysis with a UV/VIS spectrophotometers. Chlorpromazine hydrochloride was loaded into dried hydrogels to investigate the stimuli‐sensitive property at the specific pH and the drug release profile of these pH‐sensitive hydrogels in vitro. The release studies show that the highest value of release was at pH 4 which can be used for drug delivery system. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

类氨基酸基载药水凝胶敷料的制备与性能

为制备一种具有良好生物相容性、可控缓释的物理交联的水凝胶敷料,选用类氨基酸单体N-丙烯酰基甘氨酰胺（NAGA）与生物发酵产物衣康酸（IA）为单体,在紫外光条件下,通过自由基聚合,在不需要外加任何交联剂条件下即可形成水凝胶聚（N-丙烯酰基甘氨酰胺-衣康酸）（P(NAGA-IA)）。所得水凝胶具有溶胶-凝胶转变温度（UCST）、较高的水溶胀率（40倍）及力学性能（压缩模量最高540 kPa）、较优的药物负载性和缓释性,这是因为NAGA单元提供分子间多重氢键作用,进而赋予了水凝胶较优的综合性能;而IA单元赋予了聚合物的pH刺激响应性,从而可诱导药物的释放。因此,所得P (NAGA-IA)水凝胶可作敷料用于创伤治疗。     

Preparation,characterization, and drug‐release properties of poly(N‐isopropylacrylamide) microspheres having poly(itaconic acid) graft chains

An inverse suspension polymerization method for the preparation of thermoresponsive hydrogel microspheres based on N‐isopropylacrylamide was described in this article. The polymerization reaction was carried out at 200 rpm stirring rate and the microspheres obtained were in the size range of 71–500 μm in the swollen states. The particles were sieved by using ASTM sieves. The selected fraction (180–250 μm) of poly(N‐isopropylacrylamide) (PNIPAAm) microspheres was used for radiation‐induced modification with itaconic acid (IA) to obtain PNIPAAm/poly(itaconic acid) graft copolymer. Viagra and lidocaine were used as model drugs for the investigation of controlled‐release behavior of the microspheres. Incorporation of IA graft chains onto microspheres enhanced significantly the uptake of both drugs and further controlled release at specific pH values. The release studies showed that some of the basic parameters affecting the drug‐loading and ‐release behavior of the microspheres were pH, temperature, particle size, and chemical nature of drug. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1115–1124, 2005     

Colon‐specific oral delivery of vitamin B2 from poly(acrylamide‐co‐maleic acid) hydrogels: An in vitro study

Hydrogels, composed of poly(acrylamide‐co‐maleic acid) were synthesized and the release of vitamin B₂ from these gels was studied as a function of the pH of the external media, the initial amount of the drug loaded, and the crosslinking ratio in the polymer matrix. The gels containing 3.8 mg of the drug per gram gel exhibit almost zero‐order release behavior in the external media of pH 7.4 over the time interval of more than their half‐life period (t_1/2). The amount of the drug loaded into the hydrogel also affected the dynamic release of the encapsulated drug. As expected, the gels showed a complete swelling‐dependent mechanism, which was further supported by the similar morphology of the swelling and release profiles of the drug‐loaded sample. The hydrophilic nature of the drug riboflavin does not contribute toward the zero‐order release dynamics of the hydrogel system. On the other hand, the swelling osmotic pressure developed between the gels and the external phase, due to loading of the drug by equilibration of the gels in the alkaline drug solution, plays an effective role in governing the swelling and release profiles. Finally, the minimum release of the drug in the swelling media of pH 2.0 and the maximum release with zero‐order kinetics in the medium of pH 7.4 suggest that the proposed drug‐delivery devices have a significant potential to be used as an oral drug‐delivery system for colon‐specific delivery along the gastrointestinal (GI) tract. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 1133–1145, 2002; DOI 10.1002/app.10402     

Hydrogels for oral drug delivery of peptides: Synthesis and characterization

In this study hydrogels were synthesized by the copolymerization of acrylamide and itaconic acid in the presence of poly(N‐vinyl‐2‐pyrrolidone) in an aqueous medium. The incorporation of a small amount of itaconic acid resulted in the transition of the swelling behavior from Fickian to non‐Fickian. The hydrogels showed good response to the valency of the counterions and pH of the swelling media. The equilibrium water uptake increased with the pH of the external solution, thus attaining a maximum value at pH 7–8. The gels exhibited a number of deswelling–swelling cycles while maintaining mechanical strength and shape stability. The amount of itaconic acid present in the system affected the swelling behavior of the hydrogels in a rather unusual way. At pH 2.0 the equilibrium water uptake increased with the amount of acid monomer up to 15 mM, remained almost constant for a very small range of concentrations (i.e., up to 22 mM), and then finally decreased with the further increase of the acid content. However, a continuous increase was observed at the pH 7.0 of the swelling media. The hydrogels showed very poor temperature dependency and the activation energies for the samples with and without itaconic acid were 29.09 and 19.92 kJ mol^?1, respectively. Finally, the swelling and deswelling processes were explained on the basis of two different mechanisms that were followed by the gels. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1717–1729, 2002     

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     

Swelling behaviour and paracetamol release from poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide-itaconic acid) hydrogels

Copolymer hydrogels of N-isopropylacrylamide and itaconic acid (IA), crosslinked with N,N′-methylenebisacrylamide, were prepared by radical copolymerization. These hydrogels were investigated with regard to their composition to find materials with satisfactory swelling and drug release properties. A paracetamol is used as a model drug to investigate drug release profile of the hydrogels. It was found that the investigated hydrogels exhibited pH- and temperature-dependent swelling behaviour with restricted swelling and lower equilibrium degree of swelling at lower pH values and temperatures above the LCST value of PNIPAM (around 34 °C). The diffusion exponent for paracetamol release indicate that the mechanism of paracetamol release are governed by Fickian diffusion, while in all release media initial diffusion coefficient was lower than late time diffusion coefficient. Furthermore, the paracetamol release rate depends on the hydrogel degree of swelling and it increased in the first stage of diffusion process, whereas was no significant difference thereafter. The presence of the IA moieties incorporated into the network weakened the shear resistance of the hydrogels. In order to calculate the pore size the characteristic ratio for PNIPAM, C _n  = 11.7, was calculated. Based on the pore size, the investigated hydrogels can be regarded as microporous. According to the obtained results swelling behaviour, mechanical properties, drug-loading capacity and the drug release rate could be controlled by hydrogel composition and crosslinking density, which is important for application of the investigated hydrogels as drug delivery systems.     

External Stimuli‐Responsive Characteristics of Ionic Poly[(N,N‐diethylaminoethyl methacrylate)‐co‐(N‐vinyl‐2‐pyrrolidone)] Hydrogels

Summary: Polyelectrolyte hydrogels containing diprotic acid moieties sensitive to ionic strength changes of the swelling medium were synthesized from N,N‐diethylaminoethyl methacrylate (DEAEMA), N‐vinyl‐2‐pyrrolidone (VP) and itaconic acid (IA) by using ammonium persulfate (APS) as a free radical initiator in the presence of the cross‐linker, methylenebisacrylamide (MBAAm). The swelling behavior of the ionic poly[(N,N‐diethylaminoethyl methacrylate)‐co‐(N‐vinyl‐2‐pyrrolidone)] [P(DEAEMA/VP)] hydrogels were investigated in pure water; in NaCI solutions with pH 4 and 9; and in water‐acetone mixtures depending on the IA content in the hydrogel. The average molecular mass between cross‐links ( ) and polymer‐solvent interaction parameter (χ) of the hydrogels were determined from equilibrium swelling values. The pulsatile swelling behavior was also observed in response to solvent changes between the solution in water and in acetone. The equilibrium swelling ratio of these hydrogels was basically unaffected with change in temperature. The swelling variations were explained according to the swelling theory based on the hydrogel chemical structure.

Pulsatile swelling behavior of ionic P(DEAEMA/VP) hydrogels in response to solvent changes between water and acetone at 25 °C.     

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