Versatile poly(maltose) micro/nanoparticles with tunable surface functionality as a biomaterial

Maltose, a natural disaccharide, was crosslinked with divinyl sulfone to prepare poly(maltose) (p(MAL)) micro/nanoparticles via one step microemulsion system with ≥90% ± 5% yield in a size rage of 0.5–100 μm for the first time. P(MAL) was modified (m-p(MAL)) with ethylenediamine (EDA), polyethyleneimine (PEI), and taurine (TA) to render additional functionalities, that is, amine and sulfate groups. The isoelectronic point of bare p(MAL) particles were calculated at pH 2.2 ± 0.5 and was changed to 1.3 ± 0.5, 4.3 ± 1.0, and 8.1 ± 0.7 for TA (p(MAL)/TA), EDA (p(MAL)/EDA), and PEI (p(MAL)/PEI) modification, respectively. Bare p(MAL) particles were found to be biocompatible up to 2 mg/ml with hemolysis and blood clotting tests, whereas the modified p(MAL) particles were found to be biocompatible at 1 mg/ml concentration. Additionally, it was found that TA- and PEI-modified p(MAL) particles induced blood clotting mechanisms. Sodium diclofenac as model drug was released at proportions of 8.7% ± 1.3%, 3.9% ± 0.2%, 8.8% ± 0.9%, and 31.6% ± 0.4% of the loaded drug in phosphate buffered saline solution from p(MAL), p(MAL)/TA, p(MAL)/EDA, and p(MAL)/PEI, respectively. The inhibition of antimicrobial activity of p(MAL)/PEI particles at 20 mg/ml concentration for Escherichia coli and Staphylococcus aureus strain was determined as 99.86% ± 0.3% and 99.79% ± 0.25%, respectively.     

Surface‐modified pliable PDLLA/PCL/β‐TCP scaffolds as a promising delivery system for bone regeneration

Surface‐modified poly(d , l ‐lactide)/polycaprolactone/β‐tricalcium phosphate complex scaffold was fabricated in this study and we hypothesized that pliable and mechanical strong scaffold would be achieved by regulation of ternary compositions; while superficial modification strategy conduced to preserve and controlled‐release of bioactive growth factors. Properties of the composite scaffolds were systematically investigated, including mechanical properties, surface morphology, porosity, wettability, and releasing behavior. Moreover, the representative cytokine, recombinant human bone morphogenetic protein‐2 (rhBMP‐2), was loaded and implanted into muscular pouch of mouse to assess bone formation in vivo. Improved osteogenesis was achieved ascribed to both amplified β‐tricalcium phosphate (β‐TCP) content and retarded initial burst release. Particularly, scaffold doped with hydroxypropyl methylcellulose (HPMC) displayed optimal osteogenic capability. The results indicated that the PDLLA/PCL/β‐TCP complex scaffold along with HPMC‐coating and rhBMP‐2 loading was a promising candidate for bone regeneration. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40951.     

Layer by layer surface engineering of poly(lactide-co-glycolide) nanoparticles for plasmid DNA delivery

The administration of exogenous DNA has been proposed as a promising therapeutic approach for a variety of diseases. Unfortunately, exogenous DNA is unable to spontaneously penetrate mammalian cells. Although viral vectors facilitate DNA delivery at high transfection efficiency, they are restricted for in vivo applications as they could potentially induce immunogenicity and mutagenesis. To overcome the clinical challenge of viral delivery, a strategy for the encapsulation of plasmid DNA on the surface of poly(lactide-co-glycolide) nanoparticles (PLGA NPs) is shown. Plasmid green fluorescence protein (pEF-GFP) or piggybac transposon (PBCAG-eGFP) are assembled on the surface of PLGA NPs through layer by layer technique. The assembly of pEF-GFP with biopolyelectrolytes is monitored on a planar support using a quartz crystal microbalance with dissipation. The assembly of the biopolymer multilayers on PLGA NPs is followed by ζ-potential measurements. Encapsulation of plasmid DNA within the multilayers coating is confirmed by gel electrophoresis. Cellular uptake studies on HEK293 cells revealed that PLGA NPs are taken up by cells within the first 5 hr of co-culturing. Intracellular release of cargo is confirmed by GFP expression in HEK293 cells. PLGA NPs encapsulating pEF-GFP on their surface are able to transfect ~20% of HEK293 cells, while those encapsulating PBCAG-eGFP can transfect up to 75% of cells after 72 hr, causing minimum to non-cytotoxic effects.     

Functionalizable composite nanoparticles as a dual magnetic resonance imaging/computed tomography contrast agent for medical imaging

A dual contrast agent for computed tomography (CT) and magnetic resonance imaging (MRI) was synthesized via microemulsion polymerization. This contrast agent consists of Fe₃O₄ particles (d = 7 nm) with an iodine-carrying nanopolymeric shell, with overall particle sizes ranging from 50 to 250 nm. 2-Methacryloyloxyethyl(2,3,5-triiodobenzoate) was used as the monomer. Sodium oleate was used as the surfactant and its amount was varied to control the overall particle size. The composite nanoparticles were mainly characterized via dynamic light scattering, with further analyses using transmission electron microscopy and atomic force microscopy. The particles provided a highly visible contrast in CT and MR images. A template for biomedical applications was created by adding a comonomer and the particles were further functionalized with the somatostatin analogue Tyr³-octreotate. The particles were tested for specific uptake into somatostatin receptor-positive AR42J cells. The additional uptake of the functionalized particles was investigated. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47571.     

A bio-inspired gelatin-based pH- and thermal-sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells

Gelatin (Gel)-based pH- and thermal-responsive magnetic hydrogels (MH-1 and MH-2) were designed and developed as novel drug delivery systems (DDSs) for cancer chemo/hyperthermia therapy. For this goal, Gel was functionalized with methacrylic anhydride (GelMA), and then copolymerized with (2-dimethylaminoethyl) methacrylate (DMAEMA) monomer in the presence of methacrylate-end capped magnetic nanoparticles (MNPs) as well as triethylene glycol dimethacrylate (TEGDMA; as crosslinker). Afterward, a thiol-end capped poly(N-isopropylacrylamide) (PNIPAAm-SH) was synthesized through an atom transfer radical polymerization technique, and then attached onto the hydrogel through “thiol-ene” click grafting. The preliminary performances of developed MHs for chemo/hyperthermia therapy of human breast cancer was investigated through the loading of doxorubicin hydrochloride (Dox) as an anticancer agent followed by cytotoxicity measurement of drug-loaded DDSs using MTT assay by both chemo- and chemo/hyperthermia-therapies. Owing to porous morphologies of the fabricated magnetic hydrogels according to scanning electron microscopy images and strong physicochemical interactions (e.g., hydrogen bonding) the drug loading capacities of the MH-1 and MH-2 were obtained as 72 ± 1.4 and 77 ± 1.8, respectively. The DDSs exhibited acceptable pH- and thermal-triggered drug release behaviors. The MTT assay results revealed that the combination of hyperthermia therapy and chemotherapy has synergic effect on the anticancer activities of the developed DDSs.     

Fabrication of MoO3/TiO2-SiO2 with hollow spherical shape using resin as the template: Effect of decomposition of resins

Anion exchange resins are widely used in template synthesis of oxide composites. The present work is aimed to study the thermal destruction of anion exchangers with divinyl-benzene and polyacrylate matrices in order to obtain hollow spherical MoO₃/TiO₂–SiO₂ composites from these resins preliminarily saturated with paramolybate ion and coated with tetrabutoxytitanium sol with tetroethoxysilane. It is shown that the processes of resins decomposition affect the strength of spherical composites. Decomposition of the resin with a polyacrylate matrix, accompanied by random nucleation and burnout of the organic matrix at 350°C, leads to the formation of spherical oxide composites with cracks on the surface. The decomposition reactions of the resin with a divinylbenzene matrix occurring at the boundaries of the phases of cylindrical and spherical symmetry, as well as a lower burnout temperature of the organic matrix (290°C), contribute to the formation of dense MoO₃/TiO₂–SiO₂ spheres. Hollow spherical composites 0.3–0.5 mm in size are orthorhombic α-MoO₃ coated with a mixture of titanium dioxide with anatase structure and amorphous silicon dioxide.     

Green fabrication of porous chitosan/graphene oxide composite xerogels for drug delivery

Porous chitosan (CS)/graphene oxide (GO) composite xerogels were prepared through a simple and “green” freeze‐drying method. Scanning electron microscopy, Fourier transform infrared spectrometry, powder X‐ray diffraction, and compressive strength measurements were performed to characterize the microstructures and mechanical properties of as‐prepared composite xerogels. The results show that the incorporation of GO resulted in an observable change in the porous structure and an obvious increase in the compressive strength. The abilities of the composite xerogels to absorb and slowly release an anticancer drug, doxorubicin hydrochloride (DOX), in particular, the influence of different GO contents, were investigated systematically. The porous CS/GO composite xerogels exhibited efficient DOX‐delivery ability, and both the adsorption and slow‐release abilities increased obviously with increasing GO content. Additionally, the best adsorption concentration of DOX was 0.2 mg/mL, and the cumulative release percentage of DOX from the xerogels at pH4 much higher than that at pH 7.4. Therefore, such porous CS/GO composite xerogels could be promising materials as postoperation implanting stents for the design of new anticancer drug‐release carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40006.     

Textile with a hydrogel and iron oxide nanoparticles for wastewater treatment after reactive dyeing

In this work, we describe for the first time the synthesis of a hydrogel with iron oxide nanoparticles, uniformly distributed in its structure on a polyamide fabric by surface initiated photopolymerization. The type of outgoing iron ions Fe(II), Fe(III), and the combination between them influences the properties of the iron oxide particles and the obtained composite materials (PAF2, PAF3, and PAF32). All composite materials have been investigated as catalysts in heterogeneous Fenton process for treating real industrial wastewater after dyeing of cotton fabric with reactive dye Drimarene K-7B. Different conditions on the degradation of this dye have been investigated. The best result for discoloration has been obtained with PAF2 at concentration 9.4 g L⁻¹ and pH = 2.2 in the presence of H₂O₂ (93.3 mmol L⁻¹, where 78% of dye was degraded for 24 h and 90.5%-for 48 h. The high salinity of wastewaters, typical for dyeing with reactive dyes favors discoloration, while surface-active agents hinder the process. The obtained material is reusable and is more effective in less polluted water solutions. It has been found that the composite material can be used repeatedly.     

Controlled release of protein from magnetite–chitosan nanoparticles exposed to an alternating magnetic field

In this research, the controlled release of proteins from magnetite (Fe₃O₄)–chitosan (CS) nanoparticles exposed to an alternating magnetic field is reported. Fe₃O₄–CS nanoparticles were synthesized with sodium tripolyphosphate (TPP) molecules as a crosslinking reagent. Bovine serum albumin (BSA) was used as a model protein, and its controlled release studied through the variation of the frequency of an alternating magnetic field. The results show the successful coating of CS and BSA on the Fe₃O₄ nanoparticles with an average diameter of 50 nm. Intermolecular interactions of TPP with CS and BSA were confirmed by Fourier transform infrared spectroscopy. The application of low‐frequency alternating magnetic fields to such magnetic CS nanoparticles enhanced the protein release properties, in which the external magnetic fields could switch on the unloading of these nanoparticles. We concluded that enhanced BSA release from nanoparticles exposed to an alternating magnetic field is a promising method for achieving both the targeted delivery and controlled release of proteins. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43335.     

Preparation of Janus-type superparamagnetic iron oxide nanoparticles modified with functionalized PCL/PHEMA via photopolymerization for dual drug delivery

In this study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by the coprecipitation of FeCl₂˙4H₂O and FeCl₃˙6H₂O and applied as a core for preparation of Janus nanoparticles. Accordingly, freshly modified methacrylated iron oxide nanoparticles were reacted with two functionalized polymers. Acrylated poly(ε-caprolactone) (PCL) and acrylated poly(2-hydroxyethyl methacrylate) (PHEMA) were synthesized via ring-opening and free-radical polymerization, respectively, and subsequent modification with acryloyl chloride. Acrylated PCL as the hydrophobic part and acrylated PHEMA as the hydrophilic domain were grafted on the surface of methacrylated iron oxide nanoparticles with two morphologies. Pickering emulsion and solution photopolymerization reactions were used to prepare nanoparticles with “Janus” and “mixed” morphologies, respectively. The products were characterized in each step using Fourier-transform infrared spectroscopy (FT-IR), Proton nuclear magnetic resonance (¹H-NMR), thermogravimetric analysis (TGA), dynamic light scaterring (DLS), transmission electron microscope (TEM), vibrating-sample magnetometer (VSM), energy dispersive X-ray (EDX), and ultraviolet–visible spectroscopy (UV-Vis). Quercetin and 5-FU (as two anticancer drugs) were loaded in the mentioned nanoparticles, and the drug loading capacity and encapsulation efficiency (EE) of these nanoparticles were calculated. in vitro release behavior at two pH values (5.8 and 7.4) and at 37°C demonstrated that morphology can affect the release profile. Finally, rat C6 cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay for drug-free and drug-loaded nanoparticles.     

Synthesis,characterization, and drug‐release behavior of amphiphilic quaternary ammonium chitosan derivatives

A new type of amphiphilic quaternary ammonium chitosan derivative, 2‐N‐carboxymethyl‐6‐O‐diethylaminoethyl chitosan (DEAE–CMC), was synthesized through a two‐step Schiff base reaction process and applied to drug delivery. In the first step, benzaldehyde was used as a protective agent for the incorporation of diethylaminoethyl groups to form the intermediate (6‐O‐diethylaminoethyl chitosan). On the other hand, NaBH₄ was used as a reducing agent to reduce the Schiff base, which was generated by glyoxylic acid, for the further incorporation of carboxymethyl groups to produce DEAE–CMC. The structure, thermal properties, surface morphology, and diameter distribution of the resulting chitosan graft copolymers were characterized by Fourier transform infrared spectroscopy, ¹H‐NMR, thermogravimetric analysis, differential scanning calorimetry, X‐ray powder diffraction, scanning electron microscopy, and laser particle size analysis. Benefiting from the amphiphilic structure, DEAE–CMC was able to be formed into microspheres in aqueous solution with an average diameter of 4.52 ± 1.21 μm. An in vitro evaluation of these microspheres demonstrated their efficient controlled release behavior of a drug. The accumulated release ratio of vitamin B₁₂ loaded DEAE–CMC microspheres were up to 93%, and the duration was up to 15 h. The grafted polymers of DEAE–CMC were found to be blood‐compatible, and no cytotoxic effect was shown in human SiHa cells in an MTT [3‐(4, 5‐dimethyl‐thiazol‐2‐yl)‐2, 5‐diphenyltetrazolium bromide] cytotoxicity assay. These results indicate that the DEAE–CMC microspheres could be used as safe, promising drug‐delivery systems. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39890.     

Controlled release of curcumin from thiolated starch-coated iron oxide magnetic nanoparticles: An in vitro evaluation

Thiolated starch-coated iron oxide nanoparticles containing curcumin were developed to investigate their cytotoxicity on lymphocytes and cancer cell lines. These nanoparticles were prepared using different concentrations of thiolated starch to study the effect of polymer coating on various properties of nanoparticles, namely, yield percentage, particle size, drug encapsulation, etc. Zeta potential confirmed the stability of nanoparticles. The nanoparticles with 5% polymer coating showed drug encapsulation efficiency up to 78%, while loading efficiency was higher than 80%. The cytotoxicity assay revealed excellent compatibility of the system with lymphocyte cells while considerable amount of cytotoxicity on cancer cell lines.     

Synthesis and characterization of a novel stimuli‐responsive magnetite nanohydrogel based on poly(ethylene glycol) and poly(N‐isopropylacrylamide) as drug carrier

A novel stimuli‐responsive magnetite nanohydrogel (MNHG), namely [poly(ethylene glycol)‐block‐poly(N‐isopropylacrylamide‐co‐maleic anhydride)₂]‐graft‐poly(ethylene glycol)/Fe₃O₄ [PEG‐b‐(PNIPAAm‐co‐PMA)₂]‐g‐PEG/Fe₃O₄, was successfully developed. For this purpose, NIPAAm and MA monomers were block copolymerized onto PEG‐based macroinitiator through atom transfer radical polymerization technique to produce PEG‐b‐(PNIPAAm‐co‐PMA)₂. The synthesized Y‐shaped terpolymer was crosslinked through the esterification of maleic anhydride units using PEG chains to afford a hydrogel. Afterward, magnetite nanoparticles were incorporated into the synthesized hydrogel through the physical interactions. The chemical structures of all synthesized samples were characterized using Fourier transform infrared and proton nuclear magnetic resonance spectroscopies. Morphology, thermal stability, size, and magnetic properties of the synthesized MNHG were investigated. In addition, the doxorubicin hydrochloride loading and encapsulation efficiencies as well as stimuli‐responsive drug release ability of the synthesized MNHG were also evaluated. The drug‐loaded MNHG at physiological condition exhibited negligible drug release values. In contrast, at acidic (pH 5.3) condition and a little bit higher temperature (41 °C) the developed MNHG showed higher drug release values, which qualified it for cancer chemotherapy due to especial physiology of cancerous tissue in comparison with the surrounding normal tissue. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46657.     

Design and study of the potential of crosslinked cationic polymers as drug delivery systems for dermal application

Crosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium chloride or 2‐(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 °C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46420.     

Design and optimization of alginate−chitosan−pluronic nanoparticles as a novel meloxicam drug delivery system

The inflammation and pain associated with osteoarthritis are treated with nonsteroidal anti‐inflammatory drugs (NSAIDs). This treatment is accompanied by several side effects; therefore local intra articular (IA) NSAID injection can be more efficient and safe than systemic administration or topical use. In this study, alginate?chitosan?pluronic nanoparticles were considered as a new vehicle for IA meloxicam delivery. These novel nanoparticles were prepared using an ionotropic gelation method and were optimized for variables such as alginate to chitosan mass ratio, pluronic concentration, and meloxicam concentration using a 3‐factor in 3‐level Box‐Behnken design. To optimize the formulation, the dependent variables considered were particle size, zeta potential, entrapment efficiency, and mean dissolution time (MDT). The nanoparticles morphology was characterized by FESEM and AFM. The potential interactions of the drug‐polymers were investigated by ATR‐FTIR and DSC, and the delivery profile of meloxicam from the nanoparticles was obtained. The average particle size of the optimized nanoparticles was 283 nm, the zeta potential was ?16.9 mV, the meloxicam entrapment efficiency was 55%, and the MDT was 8.9 hours. The cumulative released meloxicam amount from the composite nanoparticles was 85% at pH 7.4 within 96 h. The release profile showed an initial burst release followed by a sustained release phase. The release mechanism was non‐Fickian diffusion. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42241.     

Asymmetric cyanine dyes as fluorescence probes and visible‐light photoinitiators of free‐radical polymerization processes

This article introduces asymmetric cyanine dyes employed as visible‐light photoinitiators of vinyl monomer polymerization and as fluorescence probes monitoring the progress of polymerization. A degree of polymer cure from the measurement of the changes in the probe emission intensity and position shifts during the thermally initiated polymerization of monoacrylate was obtained. A distinct increase in the intensity of the probe fluorescence was observed during polymerization when the degree of monomer conversion was gradually increasing. This effect was accompanied by a blue‐shift of the probe emission maxima. The second part of this work is focused on the possibility of an application of the tested dyes, in combination with borate anions, as photoinitiating systems. The kinetics of polymerization of trimethylolpropane triacrylate, with cyanine borates as photoinitiators, was studied by a microcalorimetric method. Asymmetric cyanine borates were found to be effective photoinitiators, and both the initiator and coinitiator concentration as well as the light intensity strongly affected the progress of photopolymerization, leading, for example, to an increase in the polymerization rate. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 99: 207–217, 2006     

Synthesis and characterization of star‐shaped PLLA with sorbitol as core and its microspheres application in controlled drug release

The purpose of this study was to investigate the suitability of a six‐arm star‐shaped poly(l ‐lactide)s (s‐PLLA) as controlled drug carriers for hydrophobic drug molecules. First, s‐PLLA was synthesized by ring‐opening polymerization of l ‐lactide using sorbitol as initiator and stannous octoate as catalyst. The structure and molecular weight (M_w) of s‐PLLA was characterized with ¹H NMR, ¹³C NMR, and GPC. Second, rifampicin (RIF) used as a model drug was encapsulated within the microspheres of s‐PLLA via oil‐in‐water emulsion/solvent evaporation technique. The morphology, drug encapsulation efficiency (EE), and in vitro release behavior of the prepared microspheres were studied in details. Results indicated that the average diameters of s‐PLLA microspheres can be controlled between 8 and 20 µm by varying the copolymer's concentration or M_w . The EE of RIF was mainly determined by the concentration of s‐PLLA. The in vitro study showed that the burst release behavior can be depressed by increasing the M_w of the s‐PLLA. Present work suggests that the synthesized s‐PLLA could be used as a new material for drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42213.     

Effect of protein adsorption on cell uptake and blood clearance of methoxy poly(ethylene glycol)‐poly(caprolactone) nanoparticles

The interactions between nanoparticles and cells or tissues are frequently mediated by different biomolecules adsorbed onto the surface of nanoparticles. In this study, several methoxy poly(ethylene glycol)‐poly(ε‐caprolactone) (mPEG‐PCL) copolymers with various mPEG/PCL ratios were synthesized and used to produce three types of mPEG‐PCL nanoparticles. The protein‐adsorption behavior of nanoparticles was assessed using fetal‐bovine‐serum (FBS) as a model protein. The cell uptake of nanoparticles at different nanoparticle doses as well as various culture periods was examined by measuring their endocytosis rate related to Hela cells cultured in FBS‐free and FBS‐contained media. The blood clearance of nanoparticles was evaluated using Kunming mice to see the differences in circulation durations of nanoparticles. Results suggest that that FBS is able to significantly regulate the cell uptake of nanoparticles in vitro, and on the other hand, the size and mPEG/PCL molar ratio of mPEG/PCL nanoparticles are closely correlated to their blood clearance. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 42884.     

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.