Horseradish peroxidase‐mediated in situ forming hydrogels from degradable tyramine‐based poly(amido amine)s

Horseradish peroxidase (HRP)‐mediated crosslinking of poly(amido amine) (PAA) copolymers was successfully applied in the preparation of in situ forming degradable hydrogels under physiological conditions. PAA copolymers containing different amounts of tyramine residues (termed as pAEEOL/TA) could be synthesized through Michael‐type addition between methylenebisacryamide and amine mixture of 2‐(2‐aminoethoxy) ethanol and tyramine (TA). Depending on the amount of TA residue, the HRP, and H₂O₂ concentration, the gelation times could be varied from about 50 to 350 s. The swelling and degradation experiments indicated under physiological conditions the pAEEOL/TA‐based hydrogels are completely degradable within 6–8 days. Rheological analysis revealed that storage modulus of the hydrogels increased from 2500 to 4100 Pa when increasing HRP concentrations. Importantly, pAEEOL/TA copolymers have low cytotoxicity. Moreover, NIH 3T3 (mouse embryonic fibroblast) cells exposed in the degradation products of pAEEOL/TA‐based hydrogels retained high cell viability, implying that the hydrogels are cyto‐biocompatible. In vitro release of methylene blue and IgG protein from pAEEOL/TA‐based hydrogels could be effectively sustained by encapsulation of the drug in the hydrogels. The results indicate that HRP‐crosslinked, degradable pAEEOL/TA‐based hydrogels are promising for biomedical applications. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

In situ injectable poly(γ‐glutamic acid) based biohydrogel formed by enzymatic crosslinking

Enzymatic crosslinking was developed to prepare in situ forming poly(γ‐glutamic acid) (γ‐PGA) based hydrogel in this study. First, the precursor of poly(γ‐glutamic acid)–tyramine (γ‐PGA–Ty) was synthesized through the reaction of carboxyl groups from a γ‐PGA backbone with tyramine. The structure of the grafted precursor was confirmed by ¹H‐NMR and Fourier transform infrared spectroscopy. After that, the crosslinking of the phenol‐containing γ‐PGA–Ty precursor was triggered by horseradish peroxidase in the presence of H₂O₂; this resulted in the formation of the γ‐PGA–Ty hydrogels. The equilibrium water content, morphology, enzymatic degradation rate, and mechanical properties of the hydrogels were characterized in detail. The data revealed that the well‐interconnected hydrogels had tunable water contents, mechanical properties, and degradability through adjustments of the composition. Furthermore, cell experiments proved the biocompatibility of the hydrogels by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. These characteristics provide an opportunity for the in situ formation of injectable biohydrogels as potential candidates in cell encapsulation and drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42301.     

Sustained delivery of hydrocortisone acetate by CS/N‐vinyl‐2‐pyrrolidone/CaCO3 microparticle hybrid hydrogels

The goal of this research is to develop a composite hydrogel system for sustained release of therapeutic agents. The hybrid hydrogels were prepared by radiation crosslinking on aqueous solution of Chitosan (CS)/N‐vinyl‐2‐pyrrolidone (NVP) with different loads of CaCO₃ in the presence of hydrocortisone acetate (HCA), an anti‐inflammatory drugs. Physical characteristics of CS/NVP/CaCO₃ were studied using X‐ray diffraction (XRD) and infrared spectrophotometery (IR). The porous structure of resulted hydrogel was confirmed by SEM micrographs. The effect of doses and calcium carbonate amount on the swelling of the hydrogels was investigated. The ability of the prepared CS/NVP/CaCO₃‐based hybrid hydrogels to be used as drug carriers for anti‐inflammatory‐specific drug delivery system was estimated using HCA as a model drug. POLYM. COMPOS., 35:1176–1183, 2014. © 2013 Society of Plastics Engineers     

Release of vitamin B12 from poly(N‐vinyl‐2‐pyrrolidone)‐crosslinked polyacrylamide hydrogels: A kinetic study

Hydrogels, composed of poly(N‐vinyl‐2‐pyrrolidone) and crosslinked polyacrylamide, were synthesized and the release of vitamin B₁₂ from these hydrogels was studied as a function of the degree of crosslinking and pH of the external swelling media. The three drug‐loaded hydrogel samples synthesized with different crosslinking ratios of 0.3, 0.7, and 1.2 (in mol %) follow different drug‐release mechanisms, that is, chain relaxation with zero‐order, non‐Fickian and Fickian, or diffusion‐controlled mechanisms. To establish a correlation between their swelling behavior and drug‐release mechanism, the former was studied by the weight‐gain method and, at the same time, the concentration of the drug released was studied colorimetrically. Various swelling parameters such as the swelling exponent n, gel‐characteristic constant k, penetration velocity v, and diffusion coefficient D were evaluated to reflect the quantitative aspect of the swelling behavior of these hydrogels. Finally, the drug‐release behavior of the hydrogels was explained by proposing the swelling‐dependent mechanism. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 1706–1714, 2000     

Thermosensitive PCL‐PEG‐PCL hydrogels: Synthesis,characterization, and delivery of proteins

In this work, a biodegradable and injectable in situ gel‐forming controlled drug delivery system based on thermosensitive poly(ε‐caprolactone)‐poly(ethylene glycol)‐poly(ε‐caprolactone) (PCL‐PEG‐PCL) hydrogels was studied. A series of PCL‐PEG‐PCL triblock copolymers were synthesized and characterized by ¹H‐NMR and gel permeation chromatography (GPC). Thermosensitivity of the PCL‐PEG‐PCL triblock copolymers was tested using the tube inversion method. The in vitro release behaviors of two model proteins, including bovine serum albumin (BSA) and horseradish peroxidase (HRP), from PCL‐PEG‐PCL hydrogels were studied in detail. The in vivo gel formation and degradation of the PCL‐PEG‐PCL triblock copolymers were also investigated in this study. The results showed that aqueous solutions of the synthesized PCL‐PEG‐PCL copolymers can form in situ gel rapidly after injection under physiological conditions. The PCL‐PEG‐PCL hydrogels showed the ability to control the release of incorporated BSA and HRP. The released HRP was confirmed to conserve its biological activity by specific enzymatic activity assay. The in vivo gel formation and degradation studies indicated that PCL‐PEG‐PCL copolymers hydrogels can sustain at least 45 days by subcutaneous injection. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PCL‐PEG‐PCL copolymers hydrogels show promise as an in situ gel‐forming controlled drug delivery system for therapeutic proteins. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Preparation and property of starch nanoparticles reinforced aldehyde–hydrazide covalently crosslinked PNIPAM hydrogels

Injectable, de‐crosslinkable, and thermosensitive hydrogels are obtained by hydrazide‐functionalized poly(N‐isopropylacrylamide) and aldehyde‐functionalized dextrin through in situ crosslinked method. Natural based and degradable starch nanoparticles (SNPs) are used as fillers in order to improve mechanical property of hydrogels. Internal morphology, dynamic modulus, thermosensitivity property, de‐crosslinking performance, drug release, and in vitro cytotoxicity of hydrogels are investigated. Results show that SNPs disperse well throughout hydrogel and have no significant influence on gelation time and de‐crosslinking performance. Elasticity property of composite hydrogel prepared from 9.0 wt % precursors with 1.5 wt % fillers is improved significantly by SNPs and maximum storage modulus reaches 399.2 kPa, but 89.6 kPa of unreinforced hydrogels. Hydrogels exhibit good thermosensitive performance at alternating cyclic temperature of 25 and 37 °C. Doxorubicin hydrochloride‐loaded hydrogels can release more than 25 days. No significant cytotoxicity to L929 fibroblast cells is observed through a CCK‐8 assay for hydrogels, precursors, and SNPs. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45761.     

p(AAm/TA)‐based IPN hydrogel films with antimicrobial and antioxidant properties for biomedical applications

Interpenetrating polymer networks (IPN), either semi‐IPN (s‐IPN) or full IPN, based on a natural polymer tannic acid (TA) and synthetic poly(acrylamide) (p(AAm)) were prepared by incorporation of TA during p(AAm) hydrogel film preparation with and without crosslinking of TA simultaneously. The synthesis of p(AAm/TA) s‐IPN and IPN hydrogels with different amounts of TA were prepared by concurrent use of redox polymerization and epoxy crosslinking. The p(AAm)‐based hydrogels were completely degraded at 37.5°C within 9 and 2 days at pHs 7.4 and 9, respectively. Biocompatibility of p(AAm), s‐IPN, and IPN were tested with WST assay and double staining, they had 75% cell viability up to almost 20 μg mL^?1 concentration against L929 fibroblast cell. Antioxidant properties of IPN and s‐IPN hydrogels were investigated with FC and ABTS^? methods. Antimicrobial properties of TA‐containing s‐IPN, and IPN hydrogels were determined against three common bacterial strains, Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, and Bacillus subtilis ATCC 6633, and it was found that p(AAm/TA)‐based s‐IPN and IPN hydrogels are effective antimicrobial and antioxidant materials. Moreover, almost up to day‐long linear TA release profiles were obtained from IPN and s‐IPN hydrogels in phosphate buffer solution at pH 7.4 at 37.5°C. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41876.     

Dual pH‐ and thermal‐responsive nanocomposite hydrogels for controllable delivery of hydrophobic drug baicalein

Hydrogels have been widely used as mild biomaterials due to their bio‐affinity, high drug loading capability and controllable release profiles. However, hydrogel‐based carriers are greatly limited for the delivery of hydrophobic payloads due to the lack of hydrophobic binding sites. Herein, nano‐liposome micelles were embedded in semi‐interpenetrating poly[(N‐isopropylacrylamide)‐co‐chitosan] (PNIPAAm‐co‐CS) and poly[(N‐isopropylacrylamide)‐co‐(sodium alginate)] (PNIPAAm‐co‐SA) hydrogels which were responsive to both temperature and pH, thereby establishing tunable nanocomposite hydrogel delivery systems. Nano‐micelles formed via the self‐assembly of phospholipid could serve as the link between hydrophobic drug and hydrophilic hydrogel due to their special amphiphilic structure. The results of transmission and scanning electron microscopies and infrared spectroscopy showed that the porous hydrogels were successfully fabricated and the liposomes encapsulated with baicalein could be well contained in the network. In addition, the experimental results of response release in vitro revealed that the smart hydrogels showed different degree of sensitiveness under different pH and temperature stimuli. The results of the study demonstrate that combining PNIPAAm‐co‐SA and PNIPAAm‐co‐CS hydrogels with liposomes encapsulated with hydrophobic drugs is a feasible method for hydrophobic drug delivery and have potential application prospects in the medical field. © 2018 Society of Chemical Industry     

Temperature‐responsive characteristics of poly(N‐isopropylacrylamide) hydrogels with macroporous structure

Macroporous poly(N‐isopropylacrylamide) (PNIPA) hydrogels were synthesized by free‐radical crosslinking polymerization in aqueous solution from N‐isopropylacrylamide monomer and N,N‐methylenebis (acrylamide) crosslinker using poly(ethylene glycol) (PEG) with three different number‐average molecular weights of 300, 600 and 1000 g mol^?1 as the pore‐forming agent. The influence of the molecular weight and amount of PEG pore‐forming agent on the swelling ratio and network parameters such as polymer–solvent interaction parameter (χ) and crosslinking density (ν_E) of the hydrogels is reported and discussed. Scanning electron micrographs reveal that the macroporous network structure of the hydrogels can be adjusted by applying different molecular weights and compositions of PEG during polymerization. At a temperature below the volume phase transition temperature, the macroporous hydrogels absorbed larger amounts of water compared to that of conventional PNIPA hydrogels, and showed higher equilibrated swelling ratios in aqueous medium. Particularly, the unique macroporous structure provides numerous water channels for water diffusion in or out of the matrix and, therefore, an improved response rate to external temperature changes during the swelling and deswelling process. These macroporous PNIPA hydrogels may be useful for potential applications in controlled release of macromolecular active agents. Copyright © 2006 Society of Chemical Industry     

In situ incorporation of monodisperse drug nanoparticles into hydrogel scaffolds for hydrophobic drug release

The effective and locally sustained delivery of hydrophobic drug with hydrogels as carriers is still a challenge owing to the inherent incompatibility of hydrophilic hydrogel network and hydrophobic drug. One promising approach is to use porous hydrogels to encapsulate and deliver hydrophobic drug in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated hydrophobic drug nanoparticles into the hydrogels because of the severe nanoparticle aggregation during the loading process. In this article, we firstly designed and fabricated efficient drug nanoparticles embedded hydrogels for hydrophobic drug delivery by incorporating monodisperse silybin (hydrophobic drug for liver protection) nanoparticles into acrylated hyaluronic acid (HA‐AC) based hydrogels through in situ cross‐linking. The silybin nanoparticles embedded hydrogel scaffolds proved to be a good sustained release system with a long period of 36 h. The drug release from this hybrid hydrogels could be modulated by tuning HA‐AC concentration, cross‐linking ratio, chain length of cross‐linker and drug loading amount. The different kinetic models were applied, and it was observed that the release profile of silybin best followed the Hixson‐Crowell model for the release of drug from the hydrogels embedding silybin nanoparticles. It could be envisioned that this process would significantly advance the potential applications of hydrogel scaffolds mediated hydrophobic drug delivery in clinical therapies. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43111.     

Dual release kinetics of antimalarials from soy protein isolate‐carbopol‐polyacrylamide based hydrogels

The currently used antimalarials suffer from drug resistance which is hampering the global management of malaria infection. To overcome drug resistance, they are administered as combination therapies which involve combination of two or more antimalarials. In this study, chloroquine diphosphate and curcumin were encapsulated onto prepared soy protein isolate‐carbopol‐polyacrylamide based hydrogels. The hydrogels were pH sensitive and exhibited enhanced swelling capability at pH 7.4. The hydrogels were biodegradable which was observed by their SEM images after drug release. The release mechanisms of both drugs were influenced by the degree of crosslinking of the soy protein isolate in the hydrogel network and the presence of the other drug in the network. The release mechanisms of both drugs from the hydrogel networks followed super case transport II. These results suggested that the hydrogels were potential dual drug delivery systems for antimalarials whereby both drugs could work over different period of time and hence, have the potential to overcome drug resistance that is common with the presently used antimalarials. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43918.     

Rheological properties and drug release characteristics of pH‐responsive hydrogels

Rheological properties, blend compatibility, and gel‐forming capacity of carbopol 940 (CP‐940), sodium alginate (NaAlg), and guar gum (GG) have been studied. These matrices have been used in delivery of timolol maleate for ophthalmic applications. Aqueous solutions of CP‐940, NaAlg, and GG in concentrations between 0.1 and 1% (wt/vol) and their blends have been prepared. In situ gel forming polymeric solutions have shown an increase in viscosity upon exposure to specific pH, ions, and temperature of the eyeball. Blend miscibility was studied by calculating polymer–polymer interaction parameters using viscosity data. Rheological properties viz., torque, viscosity, shear stress, and shear rate were obtained using a Brookfield rheometer. Viscosities of polymer solutions were obtained by a Schott Gerate viscometer. Rheological data were analyzed using Bingham, Casson Standard, and Casson Chocolate equations. The hydrogels were subjected to ex vivo release studies on timolol maleate through the excised bovine cornea using a modified Franz diffusion cell. Results were compared with the conventional drug solution. The release could be extended when the drug is incorporated into hydrogel‐forming solution. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2057–2064, 2004     

Thermal and pH dual‐responsive hydrogels based on semi‐interpenetrating network of poly(N‐isopropylacrylamide) and collagen nanofibrils

Hydrogels with environment‐sensitive properties have great potential applications in the controlled drug release field. In this paper, hybrid hydrogels with semi‐interpenetrating polymer networks (semi‐IPNs), composed of poly(N‐isopropylacrylamide) (PNIPAM) as the thermo‐sensitive component by in situ polymerization and self‐assembled collagen nanofibrils as the pH‐sensitive framework, were prepared for controlled release of methyl violet as a model drug. From Fourier transform infrared spectroscopy and scanning electron microscopy, it was indicated that the crosslinking of PNIPAM in the presence of collagen nanofibrils led to the formation of semi‐IPNs with homogeneous porous structure, and the semi‐IPNs showed improved thermal stability and elastic properties compared with the native collagen as determined using differential scanning calorimetry and rheologic measurements. Furthermore, the semi‐IPNs possessed swelling behaviors quite different from those of neat collagen or PNIPAM hydrogel under various pH values and temperatures. Correspondingly, as expected, the drug release behavior in vitro for semi‐IPNs performed variously compared with that for single‐component semi‐IPNs, which revealed the tunable performance of semi‐IPNs for release ability. Finally the thermo‐ and pH‐responsive mechanism of the semi‐IPNs was illuminated to provide guidance for the application of the thermo‐ and pH‐sensitive collagen‐based hybrid hydrogels in controlled drug delivery systems. © 2019 Society of Chemical Industry     

Near‐Infrared Light‐Triggered Dual Drug Release Using Gold Nanorod‐Embedded Thermosensitive Nanogel‐Crosslinked Hydrogels

Gold nanorod (AuNR)‐embedded poly(N‐isopropylacrylamide) (PNIPAM) hydrogels offer the possibility of achieving near‐infrared (NIR) light‐triggered drug release. In addition, using nanoparticles as a crosslinker can enhance the mechanical properties of PNIPAM hydrogels, and nanoparticle‐crosslinked hydrogels provide an important approach for dual drug release. Here, NIR light‐triggered dual drug release using AuNR‐embedded thermosensitive nanogel‐crosslinked hydrogels is reported for the first time. Two kinds of drugs are encapsulated, one in the nanogel and the other in the hydrogel. The volume phase transition of the PNIPAM hydrogels is induced by NIR light by utilizing the photothermal effect of AuNRs. By changing the number of embedded AuNRs and the intensity of NIR light, the release rate and drug quantity can be adjusted for on‐demand release. Because of its NIR light‐triggering and nanoparticle‐crosslinking capabilities, AuNR‐embedded thermosensitive nanogel‐crosslinked hydrogels may expand the application scope of hydrogels and provide enhanced properties in their applications.     

Chemically treated hard gelatin capsules for colon‐targeted drug delivery: A novel approach

Hard gelatin capsules, containing riboflavin‐loaded poly (N‐viny1–2‐pyrrolidone)‐polyacrylamide cylindrical hydrogels, were modified chemically by treating with an aqueous formaldehyde solution for the purpose of delayed release of drug along the gastrointestinal tract. The t_dis (disintegration time) of capsules was studied as a function of concentration of formaldehyde solution and the treatment time. The dynamic release of vitamin B₂ was studied as a function of crosslinking ratio of the hydrogels. The device studied seems to have potential to be used for colon‐targeted drug delivery. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2277–2282, 2003     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

Photo‐cross‐linked biodegradable thermo‐ and pH‐responsive hydrogels for controlled drug release

A new strategy was developed to prepare thermo‐ and pH‐sensitive hydrogels by the crosslinking of poly(N‐isopropylacrylamide) with a biodegradable crosslinker derived from poly(L ‐glutamic acid). Hydrogels were fabricated by exposing aqueous solutions of precursor containing photoinitiator to UV light irradiation. The swelling behaviors of hydrogels at different temperatures, pHs, and ionic strengths were examined. The hydrogels shrank under acidic condition or at temperature above their collapse temperature and would swell in neutral or basic media or at lower temperature. These processes were reversible as the pH or temperature changed. All hydrogels exhibited no weight loss in the simulated gastric fluid but degraded rapidly in the simulated intestinal condition. Bovine serum albumin were used as a model protein drug and loaded into the hydrogels. The in vitro drug release experiment was carried out at different pH values and temperatures. The pH and temperature dependent release behaviors indicated the promising application of these materials as stimuli‐responsive drug delivery vehicles. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Preparation and properties of crosslinked chitosan thermosensitive hydrogel for injectable drug delivery systems

The aim of this study was to prepare and investigate the physical properties of a thermosensitive crosslinked chitosan pregel solution, and evaluate the in vitro release profiles of macromolecules from this sol–gel transition system. Chitosan and poly (vinyl alcohol) were used to form an interpenetrating polymeric network with glutaraldehyde as the crosslinker, and glycerophosphate (GP) was added to transform the pH‐dependent solutions into thermosensitive pH‐dependent solutions. Rheological study showed that the gelation was dependent on the crosslink degree and GP concentration of the solution. The crosslinked gel had excellent mechanic properties and no apparent “pores” and formed an integrated hydrogel texture according to scanning electronic micrograph. Gas chromatography test guaranteed the medication safety with no detection of glutaraldehyde remnants in the hydrogels. In vitro release study showed that the gelation does not significantly affect the macromolecules diffusion but the crosslinking degree does. These results indicated that the hydrogel formed an intensified three‐dimensional hybrid network with interpenetrating molecules, which effectively buffered or delayed the macromolecules diffusion. The hydrogels sustained the drug release over 30 days and could be potentially used as in situ gelling implants. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1892–1898, 2006     

Glutaraldehyde‐crosslinked chitosan/hydroxyapatite bone repair scaffold and its application as drug carrier for icariin

Chitosan/hydroxyapatite (CS/HA) bone repair scaffolds crosslinked by glutaraldehyde (GA) were prepared. Characterization of morphology, structure, mechanical property, and porosity of scaffolds were evaluated. The influences of CS viscosity, HA content, and crosslinking degree on properties of scaffolds were discussed. SEM images showed that CS/HA scaffolds were porous with short rod‐like HA particles dispersing evenly in CS substrate. When [η]_CS = 5.75 × 10^?4, HA content = 65%, and crosslinking degree = 10%, the resulting CS/HA scaffolds had a flexural strength of 20 MPa and porosity of 60%, which could meet the requirements of bone repair materials. The scaffolds were used as drug carriers for icariin, and the impacts of loading time and crosslinking degree of scaffolds on drug‐loading dose were discussed. The suitable loading time was 24 h and it would be better to keep crosslinking degree no more than 10%. The drug release behavior demonstrated that the icariin‐loading CS/HA scaffolds could achieve basic drug sustained release effect. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1539–1547, 2013     

Preparation,characterization, antibacterial properties,and hemostatic evaluation of ibuprofen‐loaded chitosan/gelatin composite films

Ibuprofen‐loaded chitosan/gelatin (CS/GE) composite films were fabricated in this work. The morphology of the composite film was investigated using scanning electron microscopy. The functional groups of the composite film before and after crosslinking were characterized using Fourier transform infrared spectroscopy. Meanwhile, the mechanical properties, antibacterial performance, cytocompatibility, and hemostatic activity of the composite films were investigated. The results show that the amount of CS affected the mechanical properties and liquid uptake capacities of the composite films. The composite film showed better bactericidal activity against Staphylococcus aureus than Escherichia coli. In vitro drug‐release evaluations showed that crosslinking could control the drug‐release rate and period in wound healing. Both types of CS/GE and drug‐loaded CS/GE composite films also showed excellent cytocompatibility in cytotoxicity assays. The hemostatic evaluation indicated that the composite film crosslinked by glutaraldehyde in rabbit livers had a dramatic hemostatic efficacy. Therefore, ibuprofen‐loaded CS/GE composite films are potentially applicable as a wound dressing material. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45441.