Synthesis and properties of pH and temperature sensitive P(NIPAAm-co-DMAEMA) hydrogels

In order to investigate the influence of the continuous alkylamide sequence having pH sensitive unit on the temperature sensitivity of poly(N-isopropylacrylamide) (PNIPAAm)-based hydrogel, a monomer, N-(2-(dimethylamino) ethyl)-methacrylamide (DMAEMA), having an ethylamide group as well as an aliphatic tertiary amino group, was designed and synthesized. Hydrogels based on NIPAAm and DMAEMA were prepared via free radical polymerization. The resulted P(NIPAAm-co-DMAEMA) hydrogels were characterized in terms of maximum swelling ratio, swelling kinetics, temperature response kinetics, and effect of pH. The data obtained show that the novel hydrogels have the strong desire to respond to external temperature and pH stimuli. Importantly, because the P(NIPAAm-co-DMAEMA) hydrogels have the continuous alkylamide sequence containing isopropylamide pendant groups from PNIPAAm and ethylamide pendant groups from PDMAEMA, the incorporation of DMAEMA moiety not only provides the pH sensitivity, but also maintains the thermal properties of P(NIPAAm-co-DMAEMA) hydrogels, even as the molar percentage of DMAEMA moiety reaches 14 mol%.     

聚丙烯酰胺/聚异丙基丙烯酰胺互穿网络水凝胶的制备与性能

采用分步法用电子加速器辐射合成了聚丙烯酰胺(PAAm)/聚异丙基丙烯酰胺(PNIPAAm)互穿网络水凝胶,并考察了温度、pH值、离子强度对其溶胀性能的影响.研究表明:互穿水凝胶具有温度敏感性,且其体积相变与互穿网络中PAAm和PNIPAAm含量有关,随着网络中PAAm含量的增加水凝胶的体积相变趋于平缓,可以通过改变PAAm和PNIPAAm的组成比来控制水凝胶的体积相变行为.此外,互穿水凝胶还具有pH敏感性和一定的抗盐性.     

Synthesis, characterization and thermoreversible behaviours of poly(dimethyl siloxane)/poly(N-isopropyl acrylamide) semi-interpenetrating networks

Simultaneous and sequential poly(N-isopropyl acrylamide) (PNIPAAm)/poly(dimethyl siloxane) (PDMS) semi-interpenetrating polymer networks (IPNs) with different linear PDMS contents were prepared by free radical polymerization method. Their phase morphologies have been characterized by FTIR, DSC and SEM. The simultaneous semi-IPNs exhibited phase transition temperatures (T_pt) shifted higher temperature from glass transition temperatures (T_g) of their respective homopolymers, suggesting a heterophase morphology and only physical entanglement between the PNIPAAm network and linear PDMS with high molecular weight (Mn≈9000 g/mol). For sequential semi-IPNs, the shift of T_pts towards lower temperature suggested that the chemical interaction between the constituents of the IPNs increased with increasing PDMS content in the network. In addition, these semi-IPNs were characterized for their thermo-sensitive behaviour by equilibrium swelling studies. The results showed that incorporation of hydrophobic PDMS polymer into the thermo- and pH-sensitive PNIPAAm and P(NIPAAm-co-IA) (itaconic acid) hydrogels by semi-IPN formation decreased swelling degrees of IPNs without affecting their LCSTs whereas addition of acrylated PDMS (Tegomer V-Si 2250) as crosslinker instead of N,N^′-methylenebisacrylamide (BIS) into the structures of these hydrogels changed their LCSTs along with their swelling degrees.     

聚(N-异丙基丙烯酰胺)/聚丙烯酰胺无机/有机互穿网络水凝胶的制备及表征

通过紫外引发聚合方法制备了无机交联的聚(N-异丙基丙烯酰胺)(PNIPAAm)/有机交联的聚丙烯酰胺(PAAm)互穿网络(IPN)水凝胶.利用FTIR和SEM分别表征了凝胶的化学结构和内部形态;测定了凝胶在高温(50℃)时的退溶胀性能;利用DMA和DSC分别研究了凝胶的储能模量随温度的变化及热相转变行为.研究表明,该IPN凝胶具有温度敏感性;与未互穿的无机交联PNIPAAm凝胶相比,IPN凝胶具有多孔的网络结构和超快的响应速率,如10min内失去90%的水;其储能模量增加了3～4倍,相转变行为变弱,而最低临界溶解温度(LCST)提高了1.4℃.     

Anticancer drug release from poly(N-isopropylacrylamide/itaconic acid) copolymeric hydrogels

The drug uptake and release of anticancer drug from N-isopropylacrylamide/itaconic acid copolymeric hydrogels containing 0–3 mol% of itaconic acid irradiated at 48 kGy have been investigated. 5-Fluorouracil (5-FU) is used as a model anticancer drug. The effect of 5-FU solution on swelling characteristics of PNIPAAm and P(NIPAAm/IA) copolymeric hydrogels have also been studied. The percent swelling, equilibrium swelling, equilibrium water/5-FU content and diffusion constant values are evaluated for poly(N-isopropylacrylamide) (PNIPAAm) and poly(N-isopropylacrylamide/itaconic) (P(NIPAAm/IA)) hydrogels at 130 ppm of 5-FU solution at room temperature. Diffusion of 5-FU solution into the hydrogels has been found to be the non-Fickian type. Finally, the kinetics of drug release from the hydrogels are examined.     

Preparation and characterization of a novel IPN hydrogel memberane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAM/CMCS)

A novel type of interpenetrating polymer networks (IPN) hydrogel membrane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAm)/(CMCS) was prepared, and the effects of the feed ratio of components, swelling medium and irradiation dose on the swelling and deswelling properties of the hydrogel was systematically studied. The results showed that the introduction of CMCS did not shift the LCST (at 32 °C), which is similar to the pure PNIPAAm. The lowest swelling ratio was at pH 2. There was little influence of irradiation dose on the thermo- and pH-sensitivity of the IPN hydrogel, increasing dose only decreased the swelling ratio. The PNIPAAm:CMCS=1:4 w/w hydrogel was not thermo-sensitive in distilled water, whereas it showed a discontinuous volume phase transition in pH 2 and a continuous one in pH 8 buffer. Consequently, a combination of pH and temperature can be coupled to control the responsive behavior of these hydrogels.     

Effects of thermosensitivity of poly (N-isopropylacrylamide) hydrogel upon the duration of a lag phase at the beginning of drug release from the hydrogel

The release rates of three kinds of drugs, with different charges, from poly (N-isopropylacrylamide) hydrogels were studied. The release rate was observed to be temperature dependent for the types of drug. When the temperature was lower than the phase transition temperature, the release rate was higher at lower temperatures and increased as the temperature rose. The amount of drugs released from a poly (N-isopropylacrylamide) hydrogel disk was plotted against the square root of time. It was found that the amount of drugs released was proportional to the square root of time over a certain time interval. A lag phase was observed before the amount of drug released became proportional to the square root of time. The longest time lag was observed at the phase transition temperature of poly (N-isopropylacrylamide); LCST (33°C). This suggests that the penetration rate of water into the hydrogels is lowest at the phase transition temperature and drastically changes around it. The release rates of drugs was also affected by the charges of the drug molecules. This may be caused by the interaction of drug molecules with polymer chains. When anionic drugs are released, the electrostatic repulsion seems to act between polymer chains and drug molecules. Therefore, the lag phase observed at the beginning of the release of anionic drugs was shorter, as compared with other kinds of drugs at any temperatures between 25 and 40°C. On the other hand, when cationic drugs are released, the time lag was longer at temperatures higher than 33°C as compared with the time lag at lower temperatures. At temperatures higher than 33°C, drugs are released from the surface skin layer of the hydrogel where water molecules are less mobile than those in bulk distilled water. The drug release thus shows a long lag phase.     

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     

From poly(N‐isopropylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N‐isopropylacrylamide) triblock copolymer to poly(N‐isopropylacrylamide)‐block‐poly(ethylene oxide) hydrogels: Synthesis and rapid deswelling and reswelling behavior of hydrogels

Poly(N‐isopropylacrylamide)‐block‐poly(ethylene oxide)‐block‐poly(N‐isopropylacrylamide) (PNIPAAm‐b‐PEO‐b‐PNIPAAm) triblock copolymer was synthesized via the reversible addition‐fragmentation chain transfer/macromolecular design via the interchange of xanthate (RAFT/MADIX) process with xanthate‐terminated poly(ethylene oxide) (PEO) as the macromolecular chain transfer agent. The successful synthesis of the ABA triblock copolymer inspired the preparation of poly(N‐isopropylacrylamide)‐block‐poly(ethylene oxide) (PNIPAAm‐b‐PEO) copolymer networks with N,N′‐methylenebisacrylamide as the crosslinking agent with the similar approach. With the RAFT/MADIX process, PEO chains were successfully blocked into poly(N‐isopropylacrylamide) (PNIPAAm) networks. The unique architecture of PNIPAAm‐b‐PEO networks allows investigating the effect of the blocked PEO chains on the deswelling and reswelling behavior of PNIPAAm hydrogels. It was found that with the inclusion of PEO chains into the PNIPAAm networks as midblocks, the swelling ratios of the hydrogels were significantly enhanced. Furthermore, the PNIPAAm‐b‐PEO hydrogels displayed faster response to the external temperature changes than the control PNIPAAm hydrogel. The accelerated deswelling and reswelling behaviors have been interpreted based on the formation of PEO microdomains in the PNIPAAm networks, which could act as the hydrophilic tunnels to facilitate the diffusion of water molecules in the PNIPAAm networks. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Strategy to introduce a pendent micellar structure into poly(N-isopropylacrylamide) hydrogels

A novel class of functional poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with pendent micellar structure resulting from the pending amphiphilic polymers was designed and prepared. The influence of the pendent micellar structure on the properties of the resulted PNIPAAm hydrogels was examined in terms of morphology observed by scanning electron microscopy, thermal response through differential scanning calorimetry, and deswelling/reswelling kinetics upon external temperature changes. In comparison with the conventional ones, the novel PNIPAAm hydrogels with pendent micellar structure presented improved temperature-sensitive properties, i.e., enlarged water containing capability at room temperature, as well as improved deswelling rate upon heating.     

Effect of chemical structure on the volume-phase transition in neutral and weakly charged poly(N-alkyl(meth)acrylamide) hydrogels studied by ultrasmall-angle x-ray scattering

Neutral poly(N-isopropylacrylamide) (PIPAAm), poly(N,N-diethylacrylamide) (PDEAAm), and poly(N-isopropylmethacrylamide) (PIPMAm) hydrogels and their weakly charged counterparts prepared by copolymerizing with sodium methacrylate (x(MNa)=0,0.025,0.05) were studied using ultrasmall-angle x-ray scattering. The volume-phase transition in hydrogels was observed as an increase in the inhomogeneity correlation length of the networks. The change in inhomogeneity correlation length was abrupt in neutral PIPAAm and PIPMAm gels with increase in temperature but was continuous in neutral PDEAAm gels. Addition of ionic comonomer to the network backbone suppressed the volume-phase transition in poly(N-alkylacrylamide)s but not in PIPMAm. The observed differences in temperature-induced volume change of these three polymers in water cannot be rationalized based on their relative hydrophobicity and are instead explained by considering the hydrogen-bonding constraints on their thermal fluctuations. Both PIPAAm and PDEAAm undergo volume collapse since their thermal fluctuations are constrained by hydrogen bonding with water to an extent that beyond a critical temperature they seek entropic compensation. Although thermal fluctuations in both PIPAAm and PIPMAm are equally constrained, thermal energy of the latter can be relaxed via the rotation of alpha-methyl groups allowing it greater flexibility. Compared to N-alkylacrylamides, N-alkylmethacrylamide can thus sustain hydrogen bonding to relatively higher temperatures before seeking entropic compensation by undergoing volume collapse.     

Fast responsive poly(N-isopropylacrylamide) hydrogels prepared in phenol aqueous solutions

Fast responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with improved properties were prepared in phenol aqueous solutions with different concentrations. Due to the expanded network structure in water, the resulted hydrogels are capable of absorbing a large amount of water, i.e. exhibits a much increased swelling ratio at room temperature. Importantly, the hydrogels demonstrated much faster response rate than that of traditional PNIPAAm hydrogel upon external temperature increase.     

Swelling behavior, mechanical properties and network parameters of pH- and temperature-sensitive hydrogels of poly((2-dimethyl amino) ethyl methacrylate-co-butyl methacrylate)

In this study, swelling behavior and mechanical properties of polyelectrolyte cationic hydrogels of poly((2-dimethylamino) ethyl methacrylate) (PDMAEMA), and poly((2-dimethylamino) ethyl methacrylate-co-butyl methacrylate) (P(DMAEMA-co-BMA)), were investigated. Hydrogels were prepared by free-radical solution copolymerization of DMAEMA and BMA using ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent. Compression-strain measurements were used to analyze the mechanical properties of the hydrogels. It was found that increasing the amount of BMA comonomer in the gel structure increases the compression modulus of the material. The results of mechanical measurements were used to characterize the network structure of the hydrogels, namely the effective crosslinking density (. It was found that exceeds the theoretical crosslinking density (ν_t) calculated from the initial amount of EGDMA used for hydrogel synthesis. These hydrogels demonstrated dual sensitivity to both pH and temperature. It was shown that the pH-sensitive or temperature-sensitive phase transition behavior of the gels can be changed by changing the temperature or pH of the swelling medium at constant hydrogel composition. Increasing the temperature decreased the transition pH of the pH-sensitive phase transition. On the other hand, increasing the pH of the surrounding medium decreased the transition temperature of the temperature-sensitive phase transition. Incorporation of BMA in the gel structure has a significant effect on the transition point of the gel. Increasing the BMA content reduced the transition pH and temperature of the pH- and temperature-sensitive phase transition, respectively. The similar effect of increasing temperature or BMA content can be explained by the role of hydrophobicity in the phase transition behavior of hydrogels. Finally, the results of equilibrium swelling and compression-strain measurements were used to calculate the polymer-solvent interaction parameters of these hydrogels using the Flory-Rehner equation of equilibrium swelling.     

Water affinity and permeability in membranes of alginate-Ca2+ containing poly(n-isopropylacrylamide)

Hydrogels based on semi-interpenetrating network (semi-IPN) combining alginate-Ca²⁺ (matrix) with poly(N-isopropyl acrylamide) (PNIPAAm) were prepared and characterized in order to determine their affinity to water and their permeability to orange II as a function of temperature. Membranes of these hydrogels were obtained by gelation of the aqueous solution of alginate and PNIPAAm by the addition of CaCl₂. The presence of PNIPAAm chains inside the hydrogels alters the water affinity when compared to the pure alginate-Ca²⁺ hydrogels. Although the water uptake capability decreases above 32 °C (Low Critical Solution Temperature (LCST) of PNIPAAm in water), no shrinking of the semi-IPN hydrogels during the phase separation of the PNIPAAm was observed. The permeability of orange II as a function of temperature decreases at 32 °C and shows a dependence on the molar mass of the alginate. The partition coefficient of orange II in the hydrogel membrane, relative to water, decreases by increasing the temperature and its permeability follows a similar behavior. It was proposed that above the LCST of PNIPAAm the Alginate-Ca²⁺ networks mechanically support the collapsed PNIPAAm chains and the diffusion of orange II is minimized. The collapsing process may be followed by the formation of a complex between the carboxylic side groups of alginate and –NH–R groups of PNIPAAm. It would expose the isopropyl groups of PNIPAAm chains, providing a hydrophobic environment that minimizes the interaction between the dye and the polymeric matrix.     

Temperature-responsive chromatography using poly(N-isopropylacrylamide) hydrogel-modified silica.

Poly(N-isopropylacrylamide) (PNIPAAm) has the sharpest phase transition of the class of thermo-sensitive N-alkyl acrylamide polymers. We developed a new method of HPLC using packing materials modified with cross-linked poly(N-isopropylacrylamide) (PNIPAAm) hydrogel. A temperature-responsive surface was prepared by polymerization of NIPAAm in the presence of a cross-linker on the silica support. The surface properties and functions of the stationary phases change in response to the external temperature. Therefore it easily changes the interaction of a solute with the surface with a constant aqueous mobile phase. A temperature-responsive elution behavior was observed on the separation of steroids and PTH-amino acids. The method is expected to be applicable to separation in the pharmaceutical and biomedical fields.     

Rapid deswelling of sodium alginate/poly(N-isopropylacrylamide) semi-interpenetrating polymer network hydrogels in response to temperature and pH changes

In this study, temperature-/pH-responsive semi-interpenetrating polymer network (semi-IPN) hydrogels based on linear sodium alginate (SA) and cross-linked poly(N-isopropylacrylamide) (PNIPAAm) were prepared. The semi-IPN hydrogels reached an equilibrium deswelling state within 6 h in response to temperature or pH stimuli. Compared with the conventional PNIPAAm hydrogel, their dewelling rate in response to temperature was improved significantly, owing to the formation of a porous structure within the hydrogels in the presence of ionized SA during the polymerization process. Moreover, the deswelling process could be well described with a first-order kinetics equation and it is possible to design any hydrogel with the desired deswelling behavior through the control of the SA content in the semi-IPN hydrogels.     

Thermoresponsive poly(N-isopropylacrylamide) nanogels/poly(acrylamide) nanostructured hydrogels

Here we report the preparation and characterization of nanostructured thermo-responsive poly(acrylamide) (PAM)-based hydrogels. The addition of slightly crosslinked poly(N-isopropylacrylamide) (PNIPA) nanogels to AM reactive aqueous solution produces nanostructured hydrogels that exhibit a volume phase transition temperature (T_VPT). Their swelling kinetics, T_VPT's and mechanical properties at the equilibrium-swollen state (H_eq) are investigated as a function of the concentration of PNIPA nanogels in the nanostructured hydrogels. Nanostructured hydrogels with PNIPA nanogels/AM mass ratios of 20/80 and above exhibit higher H_eq and longer time to reach the equilibrium swelling than those of the conventional PAM hydrogels. However, the PNIPA nanogels possess thermo-responsive character missing in conventional PAM hydrogels. The T_VPT of nanostructured hydrogels depends on PNIPA nanogel content but their elastic and Young moduli are larger than those of conventional hydrogels at similar swelling ratios. Swelling kinetics, T_VPT, and mechanical properties are explained in terms of the controlled in-homogeneities introduced by the PNIPA nanogels during the polymerization.     

Atypical transition temperature dependence of poly(N‐isopropylacrylamide) and poly(N‐isopropylacrylamide‐co‐acrylamide) nanocomposites on the content of exfoliated montmorillonites

Exfoliated montmorillonite (MMT)/poly(N‐isopropylacrylamide) (PNIPAAm) and MMT/poly(N‐isopropylacrylamide‐co‐acrylamide) [P(NIPAAm‐co‐AAm)] nanocomposites were fabricated by soap‐free emulsion polymerization. Interestingly, as the content of MMT was increased from 0 to 10 wt %, the glass transition temperature of MMT/PNIPAAm was decreased from 145 to 122 °C, whereas that of the MMT/P(NIPAAm‐co‐AAm) increased from 95 to 153 °C. Although the lower critical solution temperature (LCST) of 32 °C for the MMT/PNIPAAm nanocomposites in aqueous solutions was slightly increased with the content of MMT, that of the MMT/P(NIPAAm‐co‐AAm) was decreased from 70 to 65 °C. A mechanism that the hydrogen bonds between the amide groups of PNIPAAm were interfered by the exfoliated MMT nano‐platelets for the MMT/PNIPAAm nanocomposites and the preferred absorption of acrylamide units to the MMT nanoplatelets rather than N‐isopropylacrylamide in the MMT/P(NIPAAm‐co‐AAm) nanocomposites was suggested to interpret these unusual transition behavior. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 524–530, 2009     

Influence of charge density on the swelling of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels

The volume phase transition of colloidal poly(N-isopropylacrylamide-co-acrylic acid) microgels depends in a complex way on the effective charge density within the polymer network. A series of monodisperse PNIPAM/AAc microgels with different content of acrylic acid were synthesized by surfactant-free emulsion polymerization employing sonication instead of a conventional stirring technique. Subsequently, the colloids were characterized by dynamic light scattering and electron microscopy. Potentiometric titrations provided the amount of carboxyl groups incorporated into the copolymer. The effective charge density was systematically controlled by the content of acrylic acid monomers, the pH value of the suspension, and the salt concentration. The hydrodynamic dimensions of the microgels have been measured by dynamic light scattering. The swelling/deswelling behavior is determined by the delicate balance between hydrophobic attraction of NIPAM and the repulsive electrostatic interactions of the carboxylate group of the acrylic acid moieties. Compared to their macroscopic counterparts the charged microgel particles show a significantly different swelling/deswelling behavior. This manifests in the occurrence of a two-step volume phase-transition process with increasing acrylic acid content. Hydrogen bonding has to be considered to understand this two step volume phase transition uniquely observed for colloidal microgels. Another interesting phenomenon presented here is the reversible formation of well-defined aggregates at low pH and under high salt conditions.     

Structure and properties of cellulose/poly(N‐isopropylacrylamide) hydrogels prepared by IPN strategy

Interpenetrating polymer network (IPN) strategy was developed to fabricate novel hydrogels composed of cellulose and poly(N‐isopropylacrylamide) (PNIPAAm) with high mechanical strength and adjustable thermosensitivity. Cellulose hydrogels were prepared by chemically cross‐linking cellulose in NaOH/urea aqueous solution, which were employed as the first network. The second network was subsequently obtained by in situ polymerization/cross‐linking of N‐isopropylacrylamide in the cellulose hydrogels. The results from FTIR and solid ¹³C NMR indicated that the two networks co‐existed in the IPN hydrogels, which exhibited uniform porous structure, as a result of good compatibility. The mechanical and swelling properties of IPN hydrogels were strongly dependent on the weight ratio of two networks. Their temperature‐sensitive behaviors and deswelling kinetics were also discussed. This work created double network hydrogels, which combined the advantages of natural polymer and synthesized PNIPAAm collectively in one system, leading to the controllable temperature response and improvement in the physical properties. Copyright © 2009 John Wiley & Sons, Ltd.