Polyurethane/doxorubicin nanoparticles based on electrostatic interactions as pH‐sensitive drug delivery carriers

In order to obtain a pH‐sensitive delivery carrier for doxorubicin (DOX), DOX‐loaded polyurethane (PU·DOX) nanoparticles were readily prepared in water by electrostatic interactions between amphiphilic polyurethane with carboxyl pendent groups (PU‐COOH) and doxorubicin hydrochloride (DOX·HCl). The structures of the products obtained were characterized by Fourier transform infrared spectroscopy, ¹H NMR spectroscopy, gel permeation chromatography, UV–visible spectroscopy, dynamic light scattering and transmission electron microscopy. The average hydrodynamic size of the PU·DOX nanoparticles was around 182 nm with negative surface charge (?1.1 mV) and a spherical or rodlike shape. PU·DOX nanoparticles had a higher drug‐loading content of 14.1 wt%. The in vitro drug release properties of PU·DOX nanoparticles were investigated at pH 4.0, 5.0 and 7.4, respectively. PU·DOX nanoparticles exhibited a good pH‐sensitive drug release property, but there was almost no release of DOX from PU·DOX nanoparticles at pH 7.4. The in vitro cellular uptake assay and the Cell Counting Kit‐8 assay demonstrated that PU·DOX nanoparticles had a higher level of cellular internalization and higher inhibitory effects on the proliferation of human breast cancer (MCF‐7) cells than pure DOX. The enhancement of the inhibition effects resulted from increasing apoptosis‐inducing effects on MCF‐7 cells, which was related to the enhancement of Bax expression and the reduction of Bcl‐2 expression confirmed by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay, real‐time polymerase chain reaction (PCR) assay and western blot assay. © 2018 Society of Chemical Industry     

Core/shell pH‐sensitive micelles self‐assembled from cholesterol conjugated oligopeptides for anticancer drug delivery

A doxorubicin (DOX) delivery system of pH‐sensitive micelles self‐assembled from cholesterol conjugated His₅Arg₁₀ (HR15‐Chol) and His₁₀Arg₁₀ (HR20‐Chol) has been described in this article. The amphiphilic molecules have low critical micelle concentrations of 17.8 and 28.2 μg/mL for HR15‐Chol and HR20‐Chol, respectively, even at a low pH of 5.0. The pH‐sensitive histidine segment of the polypeptide block is insoluble at pH 7.4 but becomes positively charged and soluble via protonation at pH lower than 6.0. The size and zeta potential of DOX‐loaded micelles increases with the decrease in pH. Coarse‐grained simulations were performed to verify the structure of DOX‐loaded micelles and pH sensitivity of HR15/20‐Chol. The in vitro DOX release from the micelles is significantly accelerated by decreasing pH from 7.4 to 5.0. Furthermore, DOX release from the micelles is controlled by a Fickian diffusion mechanism. These micelles have great potential applications in delivering hydrophobic anticancer drugs for improved cancer therapy. © 2009 American Institute of Chemical Engineers AIChE J, 2010     

Synthesis and in vitro assessment of novel water‐soluble dextran‐docetaxel conjugates as potential pH sensitive system for tumor‐targeted delivery

Docetaxel is a potent taxane agent mostly used in breast, lung, and prostate cancers. Its low water solubility is the major drawback that leads to use of Tween 80 as surfactant and ethanol as solvent in market formulation. But, these excipients cause severe hypersensitivity reactions. In this study, docetaxel was conjugated to biocompatible polymer, dextran 70 kDa, via a pH sensitive linker to enhance solubility and diminish the need of surfactants. Folic acid was also conjugated to dextran to provide targeted delivery. Synthesized conjugates were examined for solubility, hemo‐compatibility, stability, and cytotoxicity on MCF‐7 and MDA‐MB‐231 cell lines. Results showed about 1200‐fold enhancement in water solubility by dextran and 280‐fold by dextran‐folate conjugation. Conjugates released the drug in a pH‐dependent manner and faster hydrolysis was observed in pH 5.4 than physiological pH 7.4. Docetaxel‐dextran conjugates showed proper hemo‐compatibility and presented greater cytotoxicity than docetaxel solution. Higher cytotoxicity was seen in folate conjugated samples and the final conjugates targeted by folate would be suitable novel substitutions for currently marketed formulation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45457.     

pH‐sensitive hydrogels based on bovine serum albumin for anticancer drug delivery

Protein conjugates consisting of hydroxyethyl methacrylate and acrylic acid monomers in the presence of bovine serum albumin (BSA) were prepared by gamma irradiation to examine the potential use of these hydrogels in the controlled drug release systems. The study parameter was the BSA content in the as‐prepared conjugates. Polymers were characterized with FTIR, scanning electron microscopy (SEM), and swelling studies. The polymerization reaction caused the rearrangement of the BSA carbonyl hydrogen bonding and finally led to the modification of the BSA secondary structure as proved by FTIR. SEM proved that the prepared conjugates matrices are porous, with a three‐dimensional interconnected microstructure. The swelling kinetics of the hydrogels and the release dynamics of an anticancer model drug (flutamide) have been studied. High equilibrium swelling values, up to 1550%, could be observed and were correlated with the increase in pH, temperature, and BSA content. The mechanism of swelling changed from Fickian to non‐Fickian by reducing the acidity of the medium. This study proved that there is a direct relationship between the protein content in the conjugates and both the loaded and the released drug. These pH responsive conjugates may be exploited for the delivery of flutamide. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

pH‐/temperature‐sensitive supramolecular micelles based on cyclodextrin polyrotaxane

BACKGROUND: Based on the assembly strategy induced by host‐guest recognition in weak selective solvent, a kind of supramolecular nano‐micelles has been self‐organized from a water‐soluble diblock copolymer, poly(ethylene oxide)‐block‐poly(acrylic acid) (PEO‐b‐PAA), selectively included by ‐cyclodextrins (‐CDs). RESULTS: The spontaneous aggregation of rod‐like ‐CD/PEO‐based pseudo‐polyrotaxanes (pseudo‐PRs) drove the formation of square‐piece in aqueous media and thereafter evolved to spherical assemblies with or without hollow structure as time prolonged, which were stabilized by uncovered hydrophilic PAA segments. Such morphological evolvement attributed to hydrogen bonding between ··CCOOH in PAA and ··COH in ‐CD. However, when alkaline media was used to inhibit hydrogen bonding by ionizing ··CCOOH, the assemblies were only uniform spheres of ca. 100 nm. Meanwhile, the order stacking of PR rods became the basic building units all the time. Herein, the supramolecular PRs contributed to temperature‐response character, namely the formation of assemblies is reversible stimulated with temperature changes. Additionally, the inhibition of deceasing pH to the ionization of free PAA segments made assemblies fuse as microspheres. CONCLUSION: Such pH‐ and temperature‐sensitivity as well as the biocompatibility of components and water as media make a great potential of such nano‐particles as the biomedical materials with controlled‐release function. Copyright © 2007 Society of Chemical Industry     

pH‐sensitive polymeric particles as smart carriers for rebar inhibitors delivery in alkaline condition

The waste problem of the rebar inhibitors is very serious due to that it is a long time before they can exert their best effect in the concrete and they are kept losing all the time. However, there is still no effective solution to alleviate such situation. Meanwhile, drug delivery control technology based on environmental sensitive polymers has been successfully applied in biomedical fields. Thus, poly(acrylic acid)–acrylamide was synthesized as smart carrier for controlling rebar inhibitors delivery in concrete. Dipotassium hydrogen phosphate as model drug was encapsulated inside the polymeric particles via a self‐assembly process. The pH‐responsive activities of the polymeric particles were estimated by monitoring their swelling performances in solutions of different pH values and the drug delivery control characteristics were studied in simulated concrete pore solutions. The results indicate the polymeric particles deserve network structures with high porosity and exhibit excellent pH‐responsive activities, which can perform as perfect intelligent carriers whereas the releasing of the inhibitors follows the first‐order kinetic law. The work suggests a new application field of drug delivery control technology. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45886.     

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     

PEGylated hollow pH‐responsive polymeric nanocapsules for controlled drug delivery

Novel pH‐responsive PEGylated hollow nanocapsules (HNCaps) were fabricated through a combination of distillation–precipitation copolymerization and surface thiol–ene ‘click’ grafting reaction. For this purpose, SiO₂ nanoparticles were synthesized using the Stöber approach, and then modified using 3‐(trimethoxysilyl)propyl methacrylate (MPS). Afterward, a mixture of triethyleneglycol dimethacrylate (as crosslinker), acrylic acid (AA; as pH‐responsive monomer) and MPS‐modified SiO₂ nanoparticles (as sacrificial template) was copolymerized using the distillation–precipitation approach to afford SiO₂@PAA core–shell nanoparticles. The SiO₂ core was etched from SiO₂@PAA using HF solution, and the obtained PAA HNCaps were grafted with a thiol‐end‐capped poly(ethylene glycol) (PEG) through a thiol–ene ‘click’ reaction to produce PAA‐g‐PEG HNCaps. The fabricated HNCaps were loaded with doxorubicin hydrochloride (DOX) as a model anticancer drug, and their drug loading and encapsulation efficiencies as well as pH‐dependent drug release behavior were investigated. The anticancer activity of the drug‐loaded HNCaps was extensively evaluated using MTT assay against human breast cancer cells (MCF7). The cytotoxicity assay results as well as superior physicochemical and biological features of the fabricated HNCaps mean that the developed DOX‐loaded HNCaps have excellent potential for cancer chemotherapy. © 2020 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     

Properties of pH‐dependent tertiary amine‐based gels as potential drug delivery matrices

The rheological and morphological properties and in vitro theophylline release of tertiary amine‐based microgels were evaluated. The testing of such a formulation through in vitro diffusion experiments revealed that the release of theophylline from the microgels was pH‐dependent and differs significantly with respect to a nonresponsive gel like scleroglucan (Scl). The microgels were obtained from 2‐(diethyl amino) ethylmethacrylate (DEA) in the presence of a bifunctional crosslinker at pH 8–9. As the resulting microgels are pH‐responsive and an increase in viscosity from high to low pH range is exhibited, the in vitro release of theophylline as model drug was studied at different pHs of both the matrix and the receptor medium. The release behaviors of PDEA‐based microgels were compared to nonresponsive natural gel Scl, studied previously. For microgels, diverse release patterns were found at different acidity conditions. This observation seems to be related to complex diffusion phenomena and the different gel structure obtained for samples prepared at dissimilar pH. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 4035–4040, 2007     

Deformation kinetics of pH‐sensitive hydrogels

Polymeric gels can undergo large deformation when subjected to external solutions of varying pH. It is imperative to understand the deformation process of pH‐sensitive hydrogels for the effective application of these attractive materials in the biomedical and microfluidic fields. In the modeling of these multi‐phase materials, finite element (FE) modeling is a useful tool for the development of future applications, and it allows developers to test a wide variety of material responses in a cost‐effective and efficient manner, reducing the need to conduct extensive laboratory experiments. Although a FE user‐defined material model is available for the equilibrium state, the transient response of pH‐sensitive gels has not been effectively modeled. Based on our recent work using the heat transfer analogy to tap into the readily available coupled temperature–displacement elements available in the commercial FE software ABAQUS for simulation of the transient swelling process of neutral hydrogels, the transient swelling process of a pH‐sensitive hydrogel is studied and a FE model is further developed to simulate the transient phenomena. Some benchmark examples are investigated to demonstrate the model's capabilities in the simulation of nonlinear deformation kinetics relevant to several applications of pH‐sensitive hydrogels. © 2013 Society of Chemical Industry     

Liver‐targeting doxorubicin‐conjugated polymeric prodrug with pH‐triggered drug release profile

The aim of the research presented was to develop a potential liver‐targeting prolonged‐circulation polymeric prodrug of doxorubicin (Dox) with a pH‐triggered drug release profile. In particular, linear dendritic block copolymers composed of polyamidoamine dendrimer (PAMAM) and poly(ethylene glycol) (PEG; number‐average molecular weight of 2000 g mol^?1) with or without galactose (Gal) were synthesized. Dox was coupled to the copolymers via an acid‐labile hydrazone linker. These prodrugs, designated Gal‐PEG‐b‐PAMAM‐Dox_n and mPEG‐b‐PAMAM‐Dox_m, showed accelerated Dox release as the pH decreased from 8.0 to 5.6. Cytotoxicity of the prodrugs was lower than that of free Dox due to the gradual drug release nature. Compared to mPEG‐b‐PAMAM‐Dox_m, Gal‐PEG‐b‐PAMAM‐Dox_n showed rather high cytotoxicity against Bel‐7402, suggestive of its galactose receptor‐mediated enhanced tumor uptake. This galactose receptor‐mediated liver‐targeted profile was further confirmed by the prolonged retention time in hepatoma tissue monitored using magnetic resonance imaging. Gal‐PEG‐b‐PAMAM‐Dox_n showed better in vivo antitumor efficacy than free Dox, suggesting its great potential as a polymeric antitumor prodrug. Copyright © 2010 Society of Chemical Industry     

Polyanion/gelatin complexes as pH‐sensitive gels for controlled protein release

Polyanion/gelatin complexes including poly(methacrylic acid) (PMAA)/gelatin, poly(acrylic acid) (PAA)/gelatin, and heparin/gelatin are investigated as pH‐sensitive gels for controlled protein release. Polyanions can interact with gelatin and form amorphous precipitates within a certain pH range, which is affected by the polyanion nature. The entrapment efficiency of model proteins (myoglobin, cytochrome c, and pepsin) into the complexes is rather high (>80%). By using a modified colloid titration that mixes a solution of gelatin and model proteins titrated with polyanion solution, myoglobin and cytochrome c are found to interact with polyanions by electrostatic forces at low pH, while pepsin either interacts with the polyanion when the pH is below its isoelectric point (IEP) or complexes with gelatin at a pH above IEP_pepsin. At pH 7.4 all the complexes dissociate and proteins are rapidly released within a few hours. The complexes are stable and the proteins are retained within a certain pH range, which is related to the polyanion type (e.g., 5.0–2.0 for PMAA, 4.6–1.2 for PAA, and <4.3 for heparin). The three processes of complex formation, dissociation, and protein release have a good correlation. In addition, the protein release transition takes place within a rather narrow pH range (ca. 0.5 units) and the protein nature has little effect on the protein release profile. The high protein entrapment efficiency and good pH sensitivity of the protein release can be mainly attributed to the electrostatic attractive interactions between proteins and polyanion or gelatin. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1416–1425, 2001     

pH‐sensitive alginate/soy protein microspheres as drug transporter

The complex microspheres based on alginate (AL) and soy protein isolate (SPI) were prepared by solution blending and then Ca²⁺ crosslinking, and their function as drug carrier was explored as well. The effects of composition on the structures of microspheres were studied, and the XRD results proved the miscibility between components. Meanwhile, FTIR results suggested that such miscibility was driven by strong hydrogen bonding. Especially, the complex microsphere with equal content of AL and SPI had the best miscibility by morphological analysis, shown as a smooth and uniform surface of SEM images. The controlled release function of the complex microspheres was verified using theophylline as a drug model, that is, the swelling and drug release were affected by pH conditions and showed obvious differences under given pH of stomach, intestine, and colon. Moreover, the intestine and colon may be optimal site for prompt release of drugs. Except for the attribution of AL component to pH sensitivity, the complex microspheres also inherited the bioactivity of SPI component, which may lower irritants of drug to the tissues in body. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

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     

Acid‐sensitive magnetic nanoparticles as potential drug depots

Superparamagnetic magnetic nanoparticles were successfully functionalized with poly(methacrylic acid) via atom transfer radical polymerization, followed by conjugation to doxorubicin (Dox). Because of pH‐sensitive hydrazone linkages, the rate and extent of Dox release from the particles was higher at a lower pH and/or a higher temperature than at physiological conditions. Appropriate changes to the pH and temperature can increase the drug release from the particles. Because of the released drug, the particles were found to be cytotoxic to human breast cancer cells in vitro. Such magnetic nanoparticles, with the potential to retain drug under physiological conditions and release the drug in conditions where the pH is lower or temperature is higher, may be useful in magnetic drug targeting by reducing the side effects of the drug caused to healthy tissues. In addition, they may serve as hyperthermia agents where the high temperatures used in hyperthermia can trigger further drug release. © 2010 American Institute of Chemical Engineers AIChE J, 2011     

Synthesis of dextran‐metaxalone conjugates and study on their control drug release behaviors

Metaxalone (Met), a drug for treatment of pain and stiffness due to muscle injuries, was covalently linked to dextran via a chloroacetyl chloride spacer. The average molecular weights of dextran are 20,000 (D₂₀₀₀₀) and 40,000 (D₄₀₀₀₀), respectively, and the procedure of chemical modification for dextrans was conducted by a two‐step protocol: (1) synthesis of N‐chloroacetyl‐metaxalone; (2) synthesis of D₂₀₀₀₀‐Met and D₄₀₀₀₀‐Met. The controlled drug release studies were performed in buffer solutions with pH values of 1.1, 7.4, and 10.0. The results demonstrate that, under the same condition, the rate of release for D₂₀₀₀₀‐Met is slower than that of D₄₀₀₀₀‐Met, and more amount of Met can be detected releasing from polymer‐drug conjugate at the presence of α‐chymotrypsin in a buffer solution with pH = 8.0. It was also found that these novel polymer‐drug conjugates can effectively improve the Met's pharmacokinetics, and can increase its half‐life period. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

6‐O‐dodecyl‐chitosan carbamate–based pH‐responsive polymeric micelles for gene delivery

pH‐responsiveness is highly desirable in the stimuli‐responsive controlled release because of the distinct advantages of the fast response of pH‐triggered release and the available pH‐difference between intra‐ and extra‐cells. The present work reported a kind of novel pH‐responsive polymeric micelles, which was derived from biopolymer of 6‐O‐dodecyl‐chitosan carbamate (DCC) and evaluated as gene‐controlled release vector. The amphiphilic and amino‐rich DDC was synthesized through a protection‐graft‐deprotection method. ¹³C CP/MAS NMR, FTIR, and elemental analysis identified that dodecyls were chemoselectively grafting at 6‐hydroxyls of chitosan via the pH‐responsive bonds of carbamate, and the substitute degree (SD) was 14%. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) showed that DCC self‐assembled into polymeric micelles in aqueous solutions. The DCC polymeric micelles formed complexes with pDNA, which was elucidated by Gel retardation, TEM, and DLS. Transfection and cytotoxicity assays in A549 cells showed that DCC polymeric micelles were suitable for gene delivery. The improved transfection was attributed to the pH‐responsiveness and the moderate pDNA‐binding affinity, which led to easier release of pDNA intra‐cells. The synthesized DCC polymeric micelles might be a promising and safe candidate as nonviral vectors for gene delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42469.     

pH‐sensitive uniform gel beads for DNA adsorption

Uniform gel beads 3 mm in diameter were obtained by the suspension polymerization of an amine functionalized monomer, N‐3‐(dimethyl amino)propylmethacrylamide (DMAPM). The polymerization of DMAPM in the form of uniform droplets could be achieved at room temperature in an aqueous dispersion medium by using Ca–alginate gel as the polymerization mold. In this preparation, potassium persulfate/tetramethyl ethylenediamine and sodium alginate/calcium chloride were used as the redox initiator and the stabilizer systems, respectively. The crosslinked DMAPM gel beads exhibited pH‐sensitive, reversible swelling–deswelling behavior. The uniform gel beads were also obtained by the copolymerization of DMAPM and acrylamide (AA) in the same polymerization system. Although copolymer gel beads with higher pH sensitivities were obtained with increasing feed concentration of DMAPM, the total monomer conversion decreased. Crosslinked DMAPM and DMAPM–AA copolymer gel beads were utilized as sorbents for DNA adsorption. The gel beads produced with higher DMAPM feed concentration exhibited higher equilibrium DNA adsorption capacity. The DNA equilibrium adsorption capacities up to 50 mg DNA/g dry gel could be achieved with the crosslinked DMAPM gel beads. This value was reasonably higher relative to the previously reported adsorption capacities of known sorbents. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 3154–3161, 2000     

Enzyme‐based hydrogels containing dextran as drug delivery carriers: Preparation,characterization, and protein release

Novel enzyme‐based hydrogels for drug delivery were prepared by combining dextran with 5,5′‐azodisalicylic acid using isophorone diisocyanate as the crosslinking agent. The structure of the resultant dextran/5,5′‐azodisalicylic acid hydrogels was determined by infrared spectra, and the properties of the hydrogels were characterized by swelling measurements and scanning electron microscopy analysis. It was found that changing the concentration of 5,5′‐azodisalicylic acid affected the crosslinking density of the hydrogels and resulted in significant differences in the water swelling property and degradability of the hydrogels. Compared with their degradability, the degradation of the hydrogels seemed to be more pronounced by azoreductase in cecum content medium than that by hydrolysis in phosphate buffer solution (PBS). Also, the release rate of the protein in cecum content medium was faster than that in PBS. Attributing to the results of the resultant hydrogels described earlier, it could be concluded that dextran/5,5′‐azodisalicylic acid hydrogels could be used as a potential enzyme‐based carrier for colon‐specific drug delivery. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009