Copolymer Hydrogels Research Articles

Conducting hydrogels based on semi‐interpenetrating networks of polyaniline in poly(acrylamide‐co‐itaconic acid) matrix: synthesis and characterization

In this work, acrylamide/itaconic acid copolymeric hydrogels are prepared by free radical polymerization initiated by redox initiators of potassium persulfate and N,N,N′,N′‐tetramethyl ethylene diamine; N,N′methylene bisacrylamide was employed as a crosslinking agent. Aniline monomer was absorbed in the network of poly(acrylamide‐co‐itaconic acid) P(AAm‐co‐IA) hydrogel and followed by gamma radiation induced polymerization at room temperature. The novel semi‐interpenetrating network was comprised of linear polyaniline immersed in P(AAm‐co‐IA) matrix. Electrical conductivity of the hydrogels was measured using four‐probe technique. The conductivities for the prepared hydrogels are found to increase from 5.5 × 10−7 S cm−1 for P(AAm‐co‐IA) alone to 4.4 × 10−3 S cm−1 for semi‐interpenetrating polymer network P(AAm‐co‐IA)/polyaniline. Thus, a new composite hydrogel with good conductive properties also displaying enhanced mechanical strength and pH sensitivity was prepared. Copyright © 2017 John Wiley & Sons, Ltd.

Sorption and desorption properties of random copolymer hydrogels of N‐isopropylacrylamide and N‐ethylacrylamide: Effect of monomer composition

ABSTRACTRandom copolymer hydrogels of N‐isopropylacrylamide and N‐ethylacrylamide (NEAM) were prepared using different monomer compositions in 1:1 methanol–water mixtures. The samples were characterized by cononsolvency study in methanol‐water mixtures at various temperatures, swelling properties measurements, scanning electron microscopy. With changing ratio of the monomers in the reaction mixture, the thermal, morphological and swelling properties, varied significantly. The change in the properties with monomer composition variation are interpreted based on the different thermoresponsive characteristics and interactions of gels of N‐isopropylacrylamide and NEAM (homo‐ and copolymer gels) in water and different methanol‐water mixtures, their variable compositions in the synthesis mixtures, and their morphologies. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45176.

Construction of three-dimensional culture model of human neuroendocrine tumor BON-1 and H727 cell lines

Objective To provide new methods for the study of human neuroendocrine tumor cells in vitro by establishing three-dimensional culture models. Methods Agarose gel, alginate/polyacrylamide copolymer (ALG/PAAm) hydrogel and polyethylene glycol (PEG) crosslinked poly methyl vinyl ether maleic acid alt (PMVE-alt-MA) hydrogel were prepared. Three-dimensional culture models of human neuroendocrine tumor H727 and BON-1 cell lines based on these three materials were constructed, and the morphological changes of the models were observed by a microscope every 24 h. Results The shapes of H727 and BON-1 cells with three-dimensional culture were different from those of two-dimensional culture. After cultured for one week, H727 cells formed different multicellular spheroids with sphere diameter of 350-450, 150-250 and 50-100 μm on agarose gel, ALG/PAAm hydrogel and in PEG crosslinking PMVE-alt-MA hydrogel respectively. And BON-1 cells grew up into multicellular spheroids with sphere diameter of 150-200 μm in PEG crosslinking PMVE-alt-MA hydrogel, but they just formed irregularly shaped multicellular aggregates on the other two culture materials. Conclusion The three materials could be applied for constructing three-dimensional culture models of BON-1 and H727 cell lines. Due to their advantages and disadvantages, the appropriate culture material would be selected according to specific experimental requirements. Key words: Neuroendocrine tumor cell; Three-dimensional culture model; Culture material

Cucurbit[7]-assisted sustained release of human calcitonin from thermosensitive block copolymer hydrogel

Conventional formulations of human calcitonin (hCT), a peptide drug, normally suffer from limited therapeutic efficacy with low stability and short half-life. We have found that the fibrillation of highly amyloidogenic hCT can be inhibited by cucurbit[7] (CB[7]), an amphiphilic small molecule. Meanwhile, a thermogelling copolymer was found to be a suitable candidate for sustained delivery of peptide/protein drugs. Herein, we report a long-term delivery formulation composed of hCT-CB[7] complex and biodegradable thermogel of poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic acid −co-glycolic acid) (PLGA-PEG-PLGA). A 20wt% PLGA-PEG-PLGA solution exhibited a temperature-sensitive sol-gel transition at 35°C in phosphate buffer solution and slowly degraded over one month at neutral pH. Both the mass fraction of PLGA-PEG-PLGA copolymer and the complexation of hCT-CB[7] moderated the release process. hCT was sustainedly released over three weeks in the 20wt% hydrogel with hCT-CB[7] complex at the ratio of 1:10 or 1:25. Further considering its low cytotoxicity, the delivery system is potential for the clinical application of hCT.

Novel stimuli-responsive hydrogels derived from morpholine: synthesis, characterization and absorption uptake of textile azo dye

A new cationic monomer methacrylamido-4-(2-aminoethyl)morpholine, (MAEM) derived from morpholine was synthesized in a single step and characterized by FTIR, 1H and 13C NMR analyses. Through free radical aqueous polymerization, novel copolymeric hydrogels have been prepared successfully using methacrylamido-4-(2-aminoethyl)morpholine and acrylamide (Aam) as monomers. Later on SEM, FTIR, elemental analysis and TG instruments were used to characterize the obtained poly(acrylamide-co-methacrylamido-4-(2-aminoethyl)morpholine), poly(Aam-c-MAEM), hydrogels. Poly(Aam-c-MAEM) hydrogels were tested for swelling, diffusion and uptake of reactive orange, RO, anionic dye. In this regard, various adsorption kinetics and isotherm models as well as operation parameters were systematically examined and discussed in detail in relation to adsorption uptake such as pH of media, comonomer composition, adsorbent dosage, temperature, initial dye concentration and contact time. The description of adsorption process of RO on hydrogels was consistent with the pseudo-second-order model followed by Elovich and pseudo-first-order. The best fitting adsorption model was selected on the basis of R 2, in the order of: Temkin > D-R > Langmuir > Freundlich isotherm. The results obtained in this study demonstrate that poly(Aam-c-MAEM) hydrogels provide an excellent advantage for application of this hydrogel system in the removal of anionic textile dyes from wastewater.

Development and Validation of a Brain Phantom for Therapeutic Cooling Devices.

Tissue cooling has been proven as a viable therapy for multiple conditions and injuries and has been applied to the brain to treat epilepsy and concussions, leading to improved long-term outcomes. To facilitate the study of temperature reduction as a function of various cooling methods, a thermal brain phantom was developed and analyzed. The phantom is composed of a potassium-neutralized, superabsorbent copolymer hydrogel. The phantom was tested in a series of cooling trials using a cooling block and 37 deg water representing nondirectional blood flow ranging up to 6 gph, a physiologically representative range based on the prototype volume. Results were compared against a validated finite difference (FD) model. Two sets of parameters were used in the FD model: one set to represent the phantom itself and a second set to represent brain parenchyma. The model was then used to calculate steady-state cooling at a depth of 5 mm for all flow rates, for both the phantom and a model of the brain. This effort was undertaken to (1) validate the FD model against the phantom results and (2) evaluate how similar the thermal response of the phantom is to that of a perfused brain. The FD phantom model showed good agreement with the empirical phantom results. Furthermore, the empirical phantom agreed with the predicted brain response within 3.5% at physiological flow, suggesting a biofidelic thermal response. The phantom will be used as a platform for future studies of thermally mediated therapies applied to the cerebral cortex.

Novel Pentablock Copolymers as Thermosensitive Self-Assembling Micelles for Ocular Drug Delivery.

Many studies have focused on how drugs are formulated in the sol state at room temperature leading to the formation of in situ gel at eye temperature to provide a controlled drug release. Stimuli-responsive block copolymer hydrogels possess several advantages including uncomplicated drug formulation and ease of application, no organic solvent, protective environment for drugs, site-specificity, prolonged and localized drug delivery, lower systemic toxicity, and capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling block copolymers (such as diblock, triblock, and pentablock copolymers) with large solubility variation between hydrophilic and hydrophobic segments are capable of making temperature-dependent micellar assembles, and with further increase in the temperature, of jellifying due to micellar aggregation. In general, molecular weight, hydrophobicity, and block arrangement have a significant effect on polymer crystallinity, micelle size, and in vitro drug release profile. The limitations of creature triblock copolymers as initial burst release can be largely avoided using micelles made of pentablock copolymers. Moreover, formulations based on pentablock copolymers can sustain drug release for a longer time. The present study aims to provide a concise overview of the initial and recent progresses in the design of hydrogel-based ocular drug delivery systems.

Poly(acrylamide co-acrylic acid) for use as an in situ gelling vitreous substitute

Our objective is to improve on our previous work developing thiol-containing water-soluble copolyacrylamides that form hydrogels in situ for use as vitreous substitutes. In this study, we evaluate the incorporation of acrylic acid by varying the feed ratio of acrylic acid monomer from 0 to 40 mol% in combination with acrylamide, and bis-acryloylcystamine as the reversible cross-linker. After polymerization, the formed copolymer hydrogels were reduced with dithiothreitol to cleave the disulfide cross-linkers. Purified, lyophilized copolymers were made in a concentration range of 12.5–17.5 mg/mL (polymer in deionized water) and were gelled by oxidation. Chemical, physical, optical, and rheological characterizations along with in vitro biocompatibility studies were performed using thiazolyl blue and Electric Cell–substrate Impedance Sensing. Increasing the percentage of acrylic acid caused the polymer to gel at 12.5 mg/mL as opposed to 20 mg/mL without acrylic acid. Storage modulus values covered the range of natural vitreous (1–108 Pa). Biocompatibility testing in tissue culture with retinal pigment epithelial cells (ARPE-19) showed no toxicity at 10 mg/mL or less when compared to controls, higher concentrations. In contrast to our previously reported copolyacrylamide hydrogels, these hydrogels remain optically clear and gel at lower concentrations and have the potential for use as vitreous substitutes.

Novel hydrogels containing Nafion and poly(ethylene oxide) based block copolymers

We present a novel family of biocompatible hydrogels containing Nafion and poly(ethylene oxide) based block copolymers. In aqueous environment, thermodynamically stable ionomer-copolymer complexes are formed, as evident by light scattering and quartz crystal microbalance experiments. Moreover, incorporation of Nafion dramatically modifies the phase behaviour and the rheological properties of copolymer hydrogels. The hybrid systems not only undergo sharp and thermally reversible sol-gel transitions below the body temperature, thus retaining their injectable nature, but they also generate mechanically robust hydrogels. Moreover, ibuprofen was continuously released over a period of 26 days for the Nafion/Pluronic hydrogel, compared to only 3 days for the Nafion-free system. The hybrid gels are promising candidates for 3D-bioprinting and controlled drug release applications.

Bifunctional Poly(acrylamide) Hydrogels through Orthogonal Coupling Chemistries.

Biomaterials for cell culture allowing simple and quantitative presentation of instructive cues enable rationalization of the interplay between cells and their surrounding microenvironment. Poly(acrylamide) (PAAm) hydrogels are popular 2D-model substrates for this purpose. However, quantitative and reproducible biofunctionalization of PAAm hydrogels with multiple ligands in a trustable, controlled, and independent fashion is not trivial. Here, we describe a method for bifunctional modification of PAAm hydrogels with thiol- and amine- containing biomolecules with controlled densities in an independent, orthogonal manner. We developed copolymer networks of AAm with 9% acrylic acid and 2% N-(4-(5-(methylsulfonyl)-1,3,4-oxadiazol-2-yl)phenyl)acrylamide. The covalent binding of thiol- and amine-containing chromophores at tunable concentrations was demonstrated and quantified by UV spectroscopy. The morphology, mechanical properties, and homogeneity of the copolymerized hydrogels were characterized by scanning electron microscopy, dynamic mechanical analysis, and confocal microscopy studies. Our copolymer hydrogels were bifunctionalized with polylysine and a laminin-mimetic peptide using the specific chemistries. We analyzed the effect of binding protocol of the two components in the maturation of cultured postmitotic cortical neurons. Our substrates supported neuronal attachment, proliferation, and neuronal differentiation. We found that neurons cultured on our hydrogels bifunctionalized with ligand-specific chemistries in a sequential fashion exhibited higher maturation at comparable culture times than using a simultaneous bifunctionalization strategy, displaying a higher number of neurites, branches, and dendritic filopodia. These results demonstrate the relevance of quantitative and optimized coupling chemistries for the performance of simple biomaterials and with sensitive cell types.

Temperature-responsive copolymeric hydrogel systems synthetized by ionizing radiation

Eight different systems of hydrogel copolymers with diverse temperature responsiveness were prepared to elaborate membranes for their biomedical application. The hydrogels were synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-vinylcaprolactam) (PNVCL), which have a low critical solution temperature (LCST) close to that of the human body temperature. The networks were synthesized using gamma radiation at a dose rate of 11.2kGyh−1, and dose of 50kGy. The LCST of each system was measured by differential scanning calorimetry (DSC). The effect of using hydrophilic monomers of acrylic acid (AAc), methacrylic acid (MAAc), dimethyl acrylamide (DMAAm), and hydroxyethyl methacrylate (HEMA) for the copolymerization on the critical point was evaluated. Five viable systems were obtained, with the best hydrogel being that of poly(NIPAAm-co-DMAAm), which an LCST at 39.8°C. All the samples were characterized by FTIR-ATR, DSC, TGA, X-Ray Diffraction, and SEM. The proportion of monomers during the formation of the copolymers was decisive in the displacement of the LCST.

Preparation and properties of novel photoluminescent thermosensitive hydrogels containing a pyrene group

1-Acrylamidopyrene (AAP) was synthesized for the first time in this study. A series of thermosensitive copolymeric hydrogels were prepared by copolymerization of AAP and N-isopropyl acrylamide (NIPAAm) by UV irradiation. The effect of AAP content in the copolymeric hydrogels on the swelling ratio, mechanical properties, and drug release behavior of the hydrogels was investigated. The swelling ratios decreased from 6.5 to 4.9 (g/g) when the AAP content in the copolymeric hydrogels increased from 0.1 to 0.9 mol% owing to their increasing hydrophobicity. In addition, the thermosensitive behavior obviously diminished with increasing AAP content in the copolymeric hydrogels, but the mechanical properties and cross-linking densities of the hydrogels swollen in ethanol solution were enhanced with increasing AAP content. The swelling ratios of the hydrogels in different solvents were varied with increasing AAP content. The result of caffeine release in the hydrogels showed that when the content of AAP in the hydrogel increased, the caffeine-loading amount decreased; however, their fractional release increased. The corresponding copolymers of the NIPAAm/AAP copolymeric hydrogels were synthesized. The UV absorbance and photoluminescent (PL) behavior of AAP, NIPAAm/AAP copolymeric hydrogels, and their corresponding copolymers in some solvents with different polarities were investigated.

Hydrogels based on copolymers of 2‐hydroxyethylmethacrylate and 2‐hydroxyethylacrylate as a delivery system for proteins: Interactions with lysozyme

ABSTRACTHydrogels have attracted considerable attention due to numerous applications, in particular as contact lenses and carriers for sustained drug delivery. The aim of the present work is to characterize the interactions of copolymer hydrogels consisted of 2‐hydroxyethylmethacrylate (HEMA) and 2‐hydroxyethylacrylate (HEA) with a small protein (lysozyme) and to assess the potential applications of these hydrogels as a drug delivery system for sustained release of protein‐based therapeutics. Physicochemical properties of protein‐loaded hydrogels, as well as lysozyme in vitro loading and release and the conformation of the protein released from hydrogels were studied. The effect of copolymer composition on the protein deposition on hydrogels and protein aggregation in the presence of hydrogels was also assessed. The results show that introduction of HEA into the copolymeric hydrogels enhances their suitability as a delivery system for proteins. Copolymerisation of HEMA and HEA allows controlling the physicochemical properties of hydrogels and the protein release rate. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44768.

Robust & thermosensitive poly(ethylene glycol)-poly(ε-caprolactone) star block copolymer hydrogels

Novel 8-armed poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) star block copolymers, possessing an amide or an ester group between the PEG core and the PCL arms (PEG20K-(NHCO)-(PCL9)8 and PEG20K-(OCO)-(PCL9)8), are synthesized by ring opening polymerization of ε-caprolactone in toluene at 110 °C initiated by 8-armed star PEG20K-(NH2)8 and PEG20K-(OH)8, respectively. Compared to linear triblock copolymers with a similar hydrophilic/hydrophobic balance and molecular weight, star block copolymers show better aqueous solubility and yield more homogeneous and transparent hydrogels. PEG20K-(NHCO)-(PCL9)8 hydrogels exhibit a significantly higher storage modulus and in vitro stability in comparison with PEG20K-(OCO)-(PCL9)8 hydrogels of similar concentration and molecular weight. 1H NMR analysis of degrading hydrogel samples clearly demonstrates different degradation mechanisms for the ester and amide type star block copolymers. Their robust mechanical properties, the possibility to be formed in situ and their excellent resistance against hydrolytic degradation make these PEG-PCL star block copolymer hydrogels, especially those based on PEG20K-(NHCO)-(PCL9)8, appealing for various biomedical applications.

Stimulus-responsive block copolymer nano-objects and hydrogels via dynamic covalent chemistry.

Herein we demonstrate that dynamic covalent chemistry can be used to induce reversible morphological transitions in block copolymer nano-objects and hydrogels. Poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymer nano-objects (vesicles or worms) were prepared via polymerization-induced self-assembly. Addition of 4-carboxyphenylboronic acid (CPBA) leads to the formation of phenylboronate ester bonds with the 1,2-diol pendent groups on the hydrophilic PGMA stabilizer chains; such binding causes a subtle reduction in the packing parameter, which in turn induces either vesicle-to-worm or worm-to-sphere transitions. Moreover, CPBA binding is pH-dependent, so reversible transitions can be achieved by switching the solution pH, with relatively high copolymer concentrations leading to associated (de)gelation. This distinguishes these new physical hydrogels from the covalently cross-linked gels prepared using dynamic covalent chemistry reported in the literature.

PH responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties.

Introduction: The current work was aimed to design and synthesize novel crosslinked pH-sensitive gelatin/pectin (Ge/Pec) hydrogels using different polymeric ratios and to explore the effect of polymers and degree of crosslinking on dynamic, equilibrium swelling and in vitro release behavior of the model drug (Mannitol). Methods: The Ge/Pec based hydrogels were prepared using glutaraldehyde as the crosslinker. Various structural parameters that affect their release behavior were determined, including swelling study, porosity, sol-gel analysis, average molecular weight between crosslinks (Mc), volume fraction of polymer (V2,s), solvent interaction parameter (χ) and diffusion coefficient. The synthesized hydrogels were subjected to various characterization tools like Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and DSC differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). Results:The hydrogels show highest water uptake and release at lower pH values. The FTIR spectra showed an interaction between Ge and Pec, and the drug-loaded samples also showed the drug-related peaks, indicating proper loading of the drug. DSC and TGA studies confirmed the thermal stability of hydrogel samples, while SEM showed the porous nature of hydrogels. The drug release followed non-Fickian diffusion or anomalous mechanism. Conclusion: Aforementioned characterizations reveal the successful formation of copolymer hydrogels. The pH-sensitive swelling ability and drug release behavior suggest that the rate of polymer chain relaxation and drug diffusion from these hydrogels are comparable which also predicts their possible use for site-specific drug delivery.

Preparation and characterization of pH sensitive crosslinked Linseed polysaccharides-co-acrylic acid/methacrylic acid hydrogels for controlled delivery of ketoprofen

Some pH responsive polymeric matrix of Linseed (Linum usitatissimum), L. hydrogel (LSH) was prepared by free radical polymerization using potassium persulfate (KPS) as an initiator, N,N-methylene bisacrylamide (MBA) as a crosslinker, acrylic acid (AA) and methacrylic acid (MAA) as monomers; while ketoprofen was used as a model drug. Different formulations of LSH-co-AA and LSH-co-MAA were formulated by varying the concentration of crosslinker and monomers. Structures obtained were thoroughly characterized using Fourier transforms infrared (FTIR) spectroscopy, XRD analysis and Scanning electron microscopy. Sol-gel fractions, porosity of the materials and ketoprofen loading capacity were also measured. Swelling and in vitro drug release studies were conducted at simulated gastric fluids, i.e., pH 1.2 and 7.4. FTIR evaluation confirmed successful grafting of AA and MAA to LSH backbone. XRD studies showed retention of crystalline structure of ketoprofen in LSH-co-AA and its amorphous dispersion in LSH-co-MAA. Gel content was increased by increasing MBA and monomer content; whereas porosity of hydrogel was increased by increasing monomer concentration and decreased by increasing MBA content. Swelling of copolymer hydrogels was high at pH 7.4 and low at pH 1.2. Ketoprofen release showed an increasing trend by increasing monomer content; however it was decreased with increasing MBA content. Sustained release of ketoprofen was noted from copolymers and release followed Korsmeyer-Peppas model.

3D inkjet printing of star block copolymer hydrogels cross-linked using various metallic ions

We have, for the first time, investigated 3D inkjet printing of ionically cross-linked star block copolymer hydrogels.

SYNTHESIS AND CHARACTERIZATION STUDIES OF A SERIES OF N-VINYL IMIDAZOLE-BASED HYDROGEL

In this study, poly[( N -vinyl imidazole)-co-(2-dimethylaminoethyl methacrylate)] hydrogels with various mole percentages of monomers were prepared by free radical solution polymerization in aqueous media. N,N' -methylenebisacrylamide and 2,2'-azobisisobutyronitrile were used as cross-linker and initiator, respectively. A Fourier transform infrared spectrophotometer, scanning electron microscope and thermogravimetric analyzer were used for the characterization of the hydrogels. The swelling behavior of the hydrogels in aqueous solution were investigated at pH 6.0 and 25°C. The results showed that swelling characteristics were affected by 2-dimethylaminoethyl methacrylate content of the copolymeric hydrogel. The swelling degree of hydrogels increased from 4.2 g g –1 to 25.4 g g –1 by increasing 2-dimethylaminoethyl methacrylate concentration from 0 to 15% with respect to the total moles of monomers.

Synthesis and Drug Delivery Application of Thermo- and pH-Sensitive Hydrogels: Poly(β-CD-co-N-Isopropylacrylamide-co-IAM).

Copolymerization of N-isopropylacrylamide (NIPAM), itaconamic acid (IAM; 4-amino-2-methylene-4-oxobutanoic acid) and β-cyclodextrin was investigated in this study. β-cyclodextrin was at first modified by reacting with allyl glycidyl ether to substitute its OH end groups with moieties containing double bonds to facilitate the subsequent radical copolymerization with NIPAM and IAM. It was reported that poly(NIPAM-IAM) can respond to the change of temperature as well as pH value. In this study, the structure of β-cyclodextrin was introduced to poly(NIPAM-IAM) copolymers because of its cavity structure capable of encapsulating a variety of drug molecules. The tri-component copolymers, poly(CD-NIPAM-IAM), were synthesized with different monomeric ratios of NIPAM/IAM/β-CD and the hydrogels of the tri-component copolymers were also synthesized by additionally adding N,N′-methylenebisacrylamide as a cross-linking agent. The results show that the lower critical solution temperature (LCST) of the copolymer (or hydrogel) increases as the molar fraction of IAM increases. The transmission electron microscopic (TEM) images of linear copolymers (no cross-linking) show that molecules undergo self-assembly to have a distinct core–shell structure, compared to poly(CD-NIPAM) which contains no IAM. On the other hand, the scanning electron microscopic (SEM) images of hydrogels show that the pores gradually become sheet-like structures as the molar fraction of IAM increases to enhance the water absorption capacity. In order to exhibit the thermal and pH sensitivities of poly(CD-NIPAM-IAM) as the drug carrier, the drug release of the newly synthesized hydrogels at 37 °C and different pH values, pH = 2 and pH = 7.4, was investigated using atorvastatin which was used primarily as a lipid-lowering drug. The drug release experimental result shows that poly(CD-NIPAM-IAM) as a drug carrier was pH-sensitive and has the largest release rate at pH = 7.4 at 37 °C, indicating it is useful to release drugs in a neutral or alkaline (intestinal) environment.