Synthesis and characterization of poly(ethylene glycol)‐based thermo‐responsive polyurethane hydrogels for controlled drug release

The thermo‐responsiveness, swelling and mechanical properties of a series of novel poly(ester‐ether urethane) hydrogels have been investigated. These thermo‐sensitive hydrogels were obtained by combining hydrophobic biodegradable poly(ε‐caprolactone) diols and hydrophilic two‐, three‐ and four‐arm hydroxyl terminated poly(ethylene glycol) (PEG) of various molecular weights, using hexamethylene diisocyanate, dichloroethane as solvent and a tin‐based catalyst. The use of multifunctional PEGs leads to the formation of covalent crosslinking points allowing an additional control of the swelling capability. Thus, it was found that tuning the hydrophilic/hydrophobic balance and the crosslinking degree by changing the composition, the swelling and the thermo‐responsive behavior of these hydrogels could be modulated. The obtained hydrogels showed a volume transition at around room temperature. Therefore, and taking into account their biocompatibility, these hydrogels show promising properties for biomedical applications, such as drug delivery. Thus, the loading and release of diltiazem hydrochloride, an antihypertensive drug used as model, were investigated. These new PEG polyurethane hydrogels were able to incorporate a high amount of drug providing a sustained release after an initial burst effect. Copyright © 2013 John Wiley & Sons, Ltd.     

Novel poly(N‐isopropylacrylamide)/clay/poly(acrylamide) IPN hydrogels with the response rate and drug release controlled by clay content

Novel interpenetrating network (IPN) hydrogels (PNIPAAm/clay/PAAm hydrogels) based on poly(N‐isopropylacrylamide) (PNIPAAm) crosslinked by inorganic clay and poly(acrylamide) (PAAm) crosslinked by organic crosslinker were prepared in situ by ultraviolet (UV) irradiation polymerization. The effects of clay content on temperature dependence of equilibrium swelling ratio, deswelling behavior, thermal behavior, and the interior morphology of resultant IPN hydrogels were investigated with the help of Fourier transform infrared spectroscopy, differential scanning calorimeter (DSC), scanning electron microscope (SEM). Study on temperature dependence of equilibrium swelling ratio showed that all IPN hydrogels exhibited temperature‐sensitivity. DSC further revealed that the temperature‐sensitivity was weakened with increasing amount of clay. Study on deswelling behavior revealed that IPN hydrogels had much faster response rate when comparing with PNIPAAm/clay hydrogels, and the response rate of IPN hydrogels could be controlled by clay content. SEM revealed that there existed difference in the interior morphology of IPN hydrogels between 20 [below lower critical solution temperature (LCST)] and 50 °C (above LCST), and this difference would become obvious with a decrease in clay content. For the standpoint of applications, oscillating swelling/deswelling behavior was investigated to determine whether properties of IPN hydrogels would be stable for potential applications. Bovine serum albumin (BSA) was used as model drug for in vitro experiment, the release data suggested that the controlled drug release could be achieved by modulating clay content. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 96–106, 2009     

“Smart” carboxymethylchitosan hydrogels crosslinked with poly(N-isopropylacrylamide) and poly(acrylic acid) for controlled drug release

Carboxymethylchitosan (CMC) hydrogels containing thermo-responsive poly(N-isopropylacrylamide) (poly(NIPAAm)) and pH-responsive poly(acrylic acid) (poly(AA)) were prepared via a free radical polymerization in the presence of hexamethylene-1,6-di-(aminocarboxysulfonate) crosslinking agents. A proper ratio of CMC to NIPAAm and AA used in the reaction was investigated such that the thermo- and pH-responsive properties of the hydrogels were obtained. Water swelling of the hydrogels was improved when the solution pH was in basic conditions (pH 10) or the temperature was below its lower critical solution temperature (LCST). Effects of the change in solution temperature and pH on water swelling properties of the hydrogel as well as the releasing rate of an entrapped drug were also investigated. The hydrogels were not toxic and showed antibacterial activity against Straphylococcus aureus (S. aureus). The pH- and thermo-responsive properties of this novel “smart” hydrogel might be efficiently used as dual triggering mechanisms in controlled drug release applications.     

Synthesis and Properties of Poly(AAm‐KMA‐MA) Hydrogels

In this investigation, poly(acrylamide‐co‐potassium methacrylate‐co‐maleic acid) hydrogels, poly(AAm‐KMA‐MA) were synthesized by redox copolymerization in aqueous solution. The effect of reaction parameters, such as concentration of maleic acid, crosslinking agent, initiator and activator, on the swelling behavior was investigated in detail. The swelling/diffusion characteristics were also evaluated for 1,4‐butanediol diacrylate (BDDA) and 1,2‐ethyleneglycol dimethacrylate (EGDMA) crosslinked hydrogels having different amounts of maleic acid. The results indicate that the water diffusion of hydrogels was of a non‐Fickian type. The hydrogels were characterized by IR spectroscopy and thermogravimetric analysis (TGA). Their surface characteristics were observed by using scanning electron microscopy (SEM). Furthermore, their swelling phenomena in different pH and salt solutions and simulated biological fluids was also studied.     

Electrochromic performances and photoluminescence characteristics of versatile <Emphasis Type="Italic">N</Emphasis>-vinylimidazole-based hybrid hydrogels

We report the synthesis and multi-sensitive performances of a novel type of poly(N-vinylimidazole-co-N-methylolacrylamide) (poly(VI-co-NMA)) hydrogels. These hydrogels behave excellent electric-sensitive properties and reversible bending behaviors. The influence of various parameters such as VI concentration, electric voltage, pH, and ionic strength on the electric-sensitive properties was thoroughly investigated. To obtain electrochromic hydrogels, we further prepared colloidal crystal (CC)-loaded hydrogels in which the color of the CC can be tuned by the bending behavior of the hydrogels. Moreover, these as-prepared hydrogels present excellent adsorption performances toward quantum dots, and the photoluminescence (PL) of CdTe-doped poly(VI-co-NMA) hydrogels was investigated. We found that the PL wavelengths of the CdTe-doped hydrogels could be switched reproducibly by altering the process of swelling and deswelling. These multi-functional hydrogels coupling with the characteristics of electrochromism and PL response confer them a variety of potential applications in sensors.     

P(AA-DAC)两性聚电解质水凝胶的合成及性质

以丙烯酸(AA)和丙烯酰氧乙基三甲基氯化铵(DAC)为单体, 采用水溶液聚合法制备了P(AA-DAC)聚电解质水凝胶. 采用红外光谱和核磁共振等方法对其结构进行了表征. 研究了不同组成比的聚电解质水凝胶在去离子水、不同pH值溶液以及不同离子强度盐溶液中的溶胀行为. 研究结果表明, 摩尔比为1∶1的聚电解质水凝胶表现出典型的两性聚电解质凝胶的溶胀行为. 离子强度对其溶胀行为有着显著影响, 在溶液离子强度较高时, 凝胶网络的溶胀主要受溶剂向凝胶内部扩散所控制, 满足Fick型扩散规律n≤0.5, 随着溶液离子强度的增加, 凝胶网络平衡含水量增加, 扩散系数增大.     

Microstructured polyacrylamide hydrogels made with hydrophobic nanoparticles

Poly(methyl methacrylate) nanosize particles, made by microemulsion polymerization, were dispersed in an acrylamide aqueous solution, which was polymerized in the presence of a cross-linking agent to yield microstructured hydrogels. The kinetics of swelling and the mechanical properties of these hydrogels were investigated as a function of concentration of particles. The microstructured hydrogels exhibit higher equilibrium swelling and larger Young modulus than conventional (that is, without particles) polyacrylamide hydrogel. The morphology of the microstructured hydrogels was examined by transmission electron microscopy.     

Study on novel hydrogels based on thermosensitive PNIPAAm with pH sensitive PDMAEMA grafts

A series of novel hydrogels based on poly(N-isopropylacrylamide) (PNIPAAm) with pendant poly(N-(2-(dimethylamino) ethyl)-methacrylamide) (PDMAEMA) grafts were designed and synthesized. The influence of the pendant PDMAEMA grafts on the properties of the resulted hydrogels was examined in terms of morphology observed by scanning electron microscopy (SEM), thermal property characterized by differential scanning calorimetry (DSC) and shrinking/swelling kinetics upon external temperature changes. In comparison with the conventional PNIPAAm hydrogels, resulting hydrogels presented favorable pH sensitivity as well as improved thermosensitive properties, including enlarged water containing capability at room temperature and faster shrinking/swelling rate upon heating. In addition, fish DNA, used as a model drug, was loaded into the hydrogels, and the controlled release behavior of the drug-loaded hydrogels at different temperatures (22 and 37 °C) was further studied.     

Investigation of the swelling behavior of hydrogels derived from high-molecular-weight poly(2-ethyl-2-oxazoline)

Thermoresponsive hydrogels are of great importance as smart materials. They are usually composed of cross-linked polymers with a lower critical solution temperature (LCST). Although much is known about networks of poly(N-isopropylacrylamide), all other polymers are somewhat neglected. In this work, the temperature-dependent swelling behavior of differently cross-linked thermoresponsive poly(2-ethyl-2-oxazoline) (PEtOx) hydrogels were investigated with regard to varying parameters of the network composition. It was found that the degrees of swelling of the hydrogels converge for a certain polymer/solvent system at a distinct temperature independent of its degree of cross-linking. Furthermore, this temperature correlates with the LCST of the respective starting PEtOx. Its net chain molecular weight M_c only affects the maximum degree of swelling and thus, the swelling–deswelling rate of the hydrogel. The fundamental structure/property relations found in this study could be useful to predict the behavior of other thermoresponsive hydrogels.     

Synthesis of the Functional Hydrogels: Poly(N-isopropylacrylamide) Threaded onto the PEG Backbones Via RAFT

Functional poly(N-isopropylacrylamide) (PNIPAM) hydrogels were prepared by reversible addition fragmentation chain transfer (RAFT) polymerization of NIPAM in the presence of four-arm poly(ethylene glycol) (4A-PEG) as backbone and 4-cyanopentanoic acid dithiobenzoate functional α -cyclodextrin threaded onto the PEG as chain transfer reagent (CTA).The structure of the hydrogels was characterized in detail with FTIR techniques. The analytical results demonstrated that α -cyclodextrin remains in as-obtained hydrogels. The swelling behavior was investigated and the functional hydrogels (functional gels) showed accelerated shrinking kinetics and higher swelling ratio comparing with conventional hydrogel (CG). It could be attributed to the presence of dangling chains. The hydrogel exhibited rapid swelling and deswelling kinetics. In principle, the hydrogel might find a number of applications including an on-off system and drug delivery systems.     

Effect of the water state on the electrical bending behavior of chitosan/poly(diallyldimethylammonium chloride) hydrogels in NaCl solutions

Semi‐interpenetrating polymer network (SIPN) hydrogels, composed of chitosan (CS) and poly(diallyldimethylammonium chloride) (PDADMAC), were prepared, and they exhibited electrically sensitive behavior. The swelling behavior of the CS/PDADMAC SIPN hydrogels was studied through the immersion of the gels in various concentrations of aqueous NaCl solutions, and their responses to stimuli in electric fields were also investigated. When the swollen SIPN hydrogels were placed between a pair of electrodes, they exhibited bending behavior upon the application of an electric field, which was stepwise and dependent on the magnitude of the field. To clarify the relationship between the equilibrium‐swelling ratio and the bending behavior of the SIPN hydrogels, the state of water in the SIPN hydrogels was also investigated with differential scanning calorimetry. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 914–921, 2004     

Thermo-reversible swelling of thin hydrogel films immobilized by low-pressure plasma

Thin films of graft copolymers consisting of poly(N-isopropylacrylamide) (PNiPAAm) or poly(N,N-diethylacrylamide) (PDEAAm) as polymer backbone and poly(ethyleneglycol) as side chains were cross-linked on fluoropolymer substrates by low-pressure plasma treatment. All immobilized polymers exhibit a lower critical solution temperature between 34 and 40 degrees C. The swelling and collapsing of the hydrogels was examined with temperature-dependent spectroscopic ellipsometry. Two time ranges of swelling were observed: a fast 'dynamic' and a slow 'equilibrium' swelling. The dynamic swelling occurs within minutes or less, whereas the equilibrium swelling needs several days to complete. The surface-bound hydrogels show a shift in the transition temperature toward lower temperatures compared with the behavior in solution. Full reversibility of the dynamic swelling/collapsing was found, but the temperature scan exhibits a hysteresis between heating and cooling cycles. The PNiPAAm-containing hydrogels show a sharper transition compared to the PDEAAm-containing hydrogels, which is almost linear over a wide temperature range.     

Poly(acrylamidoglycolic acid) nanocomposite hydrogels reinforced with cellulose nanocrystals for pH-sensitive controlled release of diclofenac sodium

In this study, a non-cytotoxic and pH-sensitive poly(acrylamidoglycolic acid) based nanocomposite (PAGA-NC) hydrogels reinforced with cellulose nanocrystals (CNCs) was synthesized using redox free radical polymerization. The successful formation and crystalline behaviour of PAGA-NC hydrogels was verified by fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analyses. The results showed that morphological, rheological and mechanical properties of the PAGA-NC hydrogels were strongly influenced by the CNCs content. Moreover, swelling properties were investigated, and the results suggested that they behaved as pH sensitive manner. The in vitro MTT assay showed that the PAGA-NC hydrogels are cytocompatibile to NIH-3T3 fibroblast cells. In addition, diclofenac sodium (DCF) model drug was successfully encapsulated into these PAGA-NC hydrogels via equilibrium swelling method. The in vitro release of DCF from PAGA-NC hydrogels was retained at pH 1.2 and maximum release was observed at 7.4, revealing as potential candidates for controlled release carriers for oral drug delivery applications.     

温度和pH双敏性PVME/CMCS水凝胶辐射交联制备及其性能

以聚甲基乙烯基醚(PVME)和羧甲基壳聚糖(CMCS)为原料, 采用电子束辐照交联方法制备聚甲基乙烯基醚/羧甲基壳聚糖(PVME/CMCS)水凝胶, 研究了温度、pH值、CMCS含量等对PVME/CMCS水凝胶溶胀度的影响, 同时以5-氟尿嘧啶(5-Fu)作模型药物, 初步探讨了凝胶药物释放性能. 结果表明, 辐射剂量在20—40 kGy时, 凝胶分数随辐射剂量的增加而快速增加, 辐射40 kGy以后趋于平衡. 在相同辐射剂量下, 随着体系中CMCS含量的增加, 凝胶分数反而减少. 该水凝胶具有一定的温度和pH敏感性, 其低临界溶解温度(LCST)在35 ℃左右, 并且在相同时间内和25及37 ℃下的溶胀反复可逆, 表现出较快的响应性. pH<3.0和pH>5.0时, 溶胀度较大; pH值为3.0~5.0时, 凝胶网络由于静电力收缩, 溶胀度较小. CMCS含量的增加和辐射剂量的减小均可提高凝胶载药量. 药物释放时间可通过改变体系中CMCS的含量和辐射剂量来调节.     

PVA改性PAMPS-PAM超高力学性能双网络水凝胶的制备

采用紫外光引发聚合制备了聚乙烯醇(PVA)改性的聚(2-丙烯酰胺基-2-甲基丙磺酸)-聚丙烯酰胺(PAMPS-PAM)双网络(DN)水凝胶.测定并比较了PVA改性前后PAMPS-PAM双网络水凝胶的溶胀动力学;通过扫描电子显微镜(SEM)观察了单网络水凝胶的结构;测定PVA改性前后PAMPS-PAM双网络水凝胶的压缩及拉伸性能.结果表明,经PVA改性后的PAMPS-PAM双网络水凝胶有较高的溶胀比;0.82%PVA用量的PAMPS-PAM双网络水凝胶在90%压缩形变率下仍保持完整、最大拉伸应力达到0.5 MPa,大幅提高PAMPS-PAM双网络水凝胶的力学性能.     

Swelling characterization of novel ternary semi‐IPNs: acrylamide/1‐vinylimidazole/PEG hydrogels

New ternary semi interpenetrating polymer networks (semi‐IPNs) systems containing acrylamide (AAm), 1‐vinylimidazole (VI) and poly (ethylene glycol) (PEG) have been prepared. AAm/VI hydrogels and semi‐IPN's, poly (AAm/VI/PEG) with 0.25, 0.50, 0.75 and 1.00 g of PEG (per 1.00 g AAm) were prepared by free radical solution polymerization in aqueous solution of AAm with VI as comonomer and a multifunctional crosslinker such as 1,4 butanediol dimethacrylate (BDMA). Swelling experiments were performed in water at 25°C, gravimetrically. The influence of VI and PEG content in hydrogels were examined. AAm/VI and AAm/VI/PEG hydrogels showed large extents of swelling in aqueous media, the swelling being highly dependent on the chemical composition of the hydrogels. Percentage swelling ratio of AAm/VI hydrogels and AAm/VI/PEG hydrogels was shown as 650–4167%. The values of equilibrium water content (EWC) of the hydrogels are between 0.8990 and 0.9750. Diffusion behavior was investigated. Water diffusion into hydrogels was found to be non‐Fickian in character. Copyright © 2007 John Wiley & Sons, Ltd.     

快速响应的温敏性聚(N-异丙基丙烯酰胺)水凝胶 Ⅱ.热力学行为及水的状态研究

对使用CaCO3为成孔剂合成的快速响应的温敏性聚 (N 异丙基丙烯酰胺 ) (PNIPA)水凝胶进行了热力学行为和水的状态研究 .热力学研究表明 ,多孔结构的PNIPA水凝胶的平衡膨胀比随着反应物中CaCO3含量的增加而增加 ,随着交联剂浓度的增加而显著减小 ,但相转变温度均不受影响 .在水溶液中加入NaCl则使PNIPA水凝胶的相转变温度 (LCST)线性减小 .利用DSC分析了水凝胶中水的存在状态 ,证明了上述多孔PNIPA水凝胶中存在三种不同状态的水 ,研究了不同CaCO3粒子含量和离子强度对三种不同状态水的影响     

Swelling behaviors of thermoresponsive hydrogels cross-linked with acryloyloxyethylaminopolysuccinimide

Based on a biodegradable cross-linker, acryloyloxyethylaminopolysuccinimide (AEA-PSI), a series of looser cross-linked poly(N-isopropylacrylamide-co-acrylic acid) [P(NIPAAm-co-AAc)] hydrogels were prepared, and their water content, swelling/deswelling kinetics, and the morphology of the gels were investigated. The swelling behaviors of AEA-PSI-cross-linked P(NIPAAm/AAc) hydrogels were investigated in Dulbecco’s phosphate-buffered saline (pH = 7.4), in the distilled water, and in the simulated gastric fluids (pH = 1.2), respectively. The water contents of the hydrogels were controlled by the monomer molar ratio of NIPAAm/AAc, swelling media, and the temperature. In the swelling kinetics, all the dried hydrogels exhibited fast swelling behavior, and the swelling ratios were influenced significantly by the amounts of AEA-PSI and AAc content. The deswelling kinetics of the hydrogel were independent of the content of AAc and cross-linker. Lastly, the morphology of the hydrogels was estimated by the field scan electron microscopy.     

Radiation synthesis and characterization of poly(N,N-dimethylaminoethyl methacrylate-co-N-vinyl 2-pyrrolidone) hydrogels

In this study, radiation synthesis and characterization of swelling behavior and network structure of poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), and poly(N,N-dimethylaminoethyl methacrylate-co-N-vinyl 2-pyrrolidone) (P(DMAEMA-co-VP)), hydrogels were investigated. PDMAEMA and P(DMAEMA-co-VP) hydrogels in the rod forms were prepared by irradiating the ternary mixtures of DMAEMA/VP/cross-linking agent, ethyleneglycol dimethacrylate (EGDMA), by gamma rays at ambient temperature. In composition ranges where the three components were completely miscible, water was also added to the ternary mixture to provide the formation of homogeneous polymerization and gelation. The influence of irradiation dose, comonomer, VP, and cross-linking agent, EGDMA, content on the total percentage gelation and monomer conversion were investigated. The effect of pH and temperature on the swelling behavior of hydrogels have also been examined. Hydrogels showed typical pH response and temperature responses, such as low-pH and low temperature swelling and high-pH and high temperature deswelling. Polymer-solvent interaction parameter (χ) and enthalpy and entropy changes appearing in the χ parameter for the P(DMAEMA-co-VP)-water system were determined by using Flory-Rehner theory of swelling equilibrium. The negative values for ΔH and ΔS indicate that prepared pure PDMAEMA and P(DMAEMA-co-VP) hydrogels have lower critical solution temperature (LCST) and Flory-Rehner theory of swelling equilibrium provides a satisfactory agreement to the experimental swelling data of the hydrogels.     

New semi-interpenetrating network hydrogels: synthesis, characterization and properties

Amphiphilic hydrogels composed of aliphatic polyesters and poly(ethylene glycol) have potential applications in drug delivery, tissue engineering and other biomedical devices due to their advantageous biological properties, biocompatibility and biodegradability. However, they also exhibit some shortcomings in terms of their reactivity, swelling and mechanical properties. To address these limitations, new semi-interpenetrating network (semi-IPN) hydrogels based on poly(ethylene glycol)-co-poly(epsilon-caprolactone) (PEG-PCL) diacrylate macromer and hydroxypropyl guar gum (HPGG) were prepared by a low intensity ultraviolet (UV) light irradiation method, and characterized by FT-IR, DSC and WAXD analysis. Their properties were evaluated by investigating the swelling kinetics, dynamic mechanical rheology and the release behavior for bovine serum albumin (BSA). It was found that the introduction of the semi-IPN structure and HPGG decreased the crystallinity of PEG segments in the hydrogel, and improved the swelling and mechanical properties of the hydrogel, as well as lowered the release percentage of BSA from the hydrogel. Such hydrogel materials may have more advantages as a potentially interesting platform for the design of medical devices.The elastic modulus (G') and viscous modulus (G') as a function of frequency for various hydrogel samples.