Organic–inorganic hybrid hydrogels involving poly(N‐isopropylacrylamide) and polyhedral oligomeric silsesquioxane: Preparation and rapid thermoresponsive properties

3‐Acryloxypropylhepta(3,3,3‐trifluoropropyl) polyhedral oligomeric silsesquioxane (POSS) was synthesized and used as a modifier to improve the thermal response rates of poly(N‐isopropylacrylamide) (PNIPAM) hydrogel. The radical copolymerization among N‐isopropylacrylamide (NIPAM), the POSS macromer and N,N′‐methylenebisacrylamide was performed to prepare the POSS‐containing PNIPAM cross‐linked networks. Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) showed that the POSS‐containing PNIPAM networks displayed the enhanced glass transition temperatures (T_g's) and improved thermal stability when compared with plain PNIPAM network. The POSS‐containing PNIPAM hydrogels exhibited temperature‐responsive behavior as the plain PNIPAM hydrogels. It is noted that with the moderate contents of POSS, the POSS‐containing PNIPAM hydrogels displayed much faster response rates in terms of swelling, deswelling, and re‐swelling experiments than plain PNIPAM hydrogel. The improved thermoresponsive properties of hydrogels have been interpreted on the basis of the formation of the specific microphase‐separated morphology in the hydrogels, that is, the POSS structural units in the hybrid hydrogels were self‐assembled into the highly hydrophobic nanodomains, which behave as the microporogens and promote the contact of PNIPAM chains and water. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 504–516, 2009     

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels formed by macrocrosslinker as drug delivery system

Dual thermo‐ and pH‐sensitive network‐grafted hydrogels made of poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) network and poly(N‐isopropylacrylamide) (PNIPAM) grafting chains were successfully synthesized by the combination of atom transfer radical polymerization (ATRP), reversible addition‐fragmentation chain transfer (RAFT) polymerization, and click chemistry. PNIPAM having two azide groups at one chain end [PNIPAM‐(N₃)₂] was prepared with an azide‐capped ATRP initiator of N,N‐di(β‐azidoethyl) 2‐chloropropionylamide. Alkyne‐pending poly(N,N‐dimethylaminoethyl methacrylate‐co‐propargyl acrylate) [P(DMAEMA‐co‐ProA)] was obtained through RAFT copolymerization using dibenzyltrithiocarbonate as chain transfer agent. The subsequent click reaction led to the formation of the network‐grafted hydrogels. The influences of the chemical composition of P(DMAEMA‐co‐ProA) on the properties of the hydrogels were investigated in terms of morphology and swelling/deswelling kinetics. The dual stimulus‐sensitive hydrogels exhibited fast response, high swelling ratio, and reproducible swelling/deswelling cycles under different temperatures and pH values. The uptake and release of ceftriaxone sodium by these hydrogels showed both thermal and pH dependence, suggesting the feasibility of these hydrogels as thermo‐ and pH‐dependent drug release devices. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

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     

A novel sodium carboxymethylcellulose/poly(N‐isopropylacrylamide)/Clay semi‐IPN nanocomposite hydrogel with improved response rate and mechanical properties

A novel semi‐IPN nanocomposite hydrogel (CMC/PNIPA/Clay hydrogel) based on linear sodium carboxymethylcellulose (CMC) and poly(N‐isopropylacrylamide) (PNIPA) crosslinked by inorganic clay was prepared. The structure and morphology of these hydrogels were investigated and their swelling and deswelling kinetics were studied in detail. TEM images showed that the clay was substantially exfoliated to form nano‐dimension platelets dispersed homogeneously in the hydrogels and acted as a multifunctional crosslinker. The CMC/PNIPA/Clay hydrogels swell faster than the corresponding PNIPA/Clay hydrogels at pH 7.4, whereas they swell slower than the PNIPA/Clay hydrogels at pH 1.2. The CMC/PNIPA/Clay nanocomposite hydrogels showed much higher deswelling rates, which was ascribed to more passway formed in these hydrogels for water to diffuse in and out. The deswelling process of the hydrogels could be approximately described by the first‐order kinetic equation and the deswelling rate decreased with increasing clay content. The mechanical properties of the CMC/PNIPA/Clay nanocomposite hydrogels were analyzed based on the theory of rubber elasticity. It was found that with increasing clay content, the effective crosslink chain density, v_e, increased whereas the molecular weight of the chains between crosslinks M_c decreased. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1546–1555, 2008     

Preparation and properties of chitosan‐poly(N‐isopropylacrylamide) semi‐IPN hydrogels

Chitosan (CS), CS‐poly(N‐isopropylacrylamide)(PNIPAM) and their dyed (pyrene) hydrogels were prepared using glutaraldehyde (Glu) as a crosslinker. The gelation rate, swelling behaviors in ethanol/water mixtures, electricity‐induced contraction and thermoresponse of the gels were investigated using fluorescence probe technique. Results showed that CS/Glu, and PNIPAM‐containing CS/Glu gels exhibited similar properties in all aspects examined, except that the transparence of the CS‐PNIPAM/Glu gel is very dependent upon the temperature. The CS‐PNIPAM/Glu gel is transparent below 30°C, whereas opaque above 32°C. It is expected that this observation may be useful for the design and preparation of new kinds of hydrogel devices. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 474–481, 2000     

The incorporation of carboxylate groups into temperature‐responsive poly(N‐isopropylacrylamide)‐based hydrogels promotes rapid gel shrinking

Aqueous gel deswelling rates for copolymer hydrogels comprising N‐isopropylacrylamide (IPAAm) and 2‐carboxyisopropylacrylamide (CIPAAm) in response to increasing temperatures were investigated. Compared with pure IPAAm‐based gels, IPAAm–CIPAAm gels shrink very rapidly in response to small temperature increases across their lower critical solution temperature (their volume is reduced by five‐sixths within 60 s). Shrinking rates for these hydrogels increase with increasing CIPAAm content. In contrast, structurally analogous IPAAm–acrylic acid (AAc) copolymer gels lose their temperature sensitivity with the introduction of only a few mole percent of AAc. Additionally, deswelling rates of IPAAm–AAc gels decrease with increasing AAc content. These results indicate that IPAAm–CIPAAm copolymer gels behave distinctly from IPAAm–AAc systems even if both comonomers, CIPAAm and AAc, possess carboxylic acid groups. Thus, we propose that the sensitive deswelling behavior for IPAAm–CIPAAm gels results from strong hydrophobic chain aggregation maintained between network polymer chains due to the similar chemical structures of CIPAAm and IPAAm. This structural homology facilitates aggregation of chain isopropylamide groups for both IPAAm and CIPAAm sequences with increasing temperature. The incorporation of AAc, however, shows no structural homology to IPAAm, inhibiting chain aggregation and limiting collapse. A functionalized temperature‐sensitive poly(N‐isopropylacrylamide) hydrogel containing carboxylic acid groups is possible with CIPAAm, producing rapid and large volume changes in response to smaller temperature changes. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 335–342, 2001     

Reducibly degradable hydrogels of PNIPAM and PDMAEMA: Synthesis,stimulus‐response and drug release

Reducibly degradable hydrogels of poly(N‐isopropylacrylamide) (PNIPAM) and poly(N,N‐dimethylaminoethyl methacrylate) (PDMAEMA) were synthesized by the combination of reversible addition‐fragmentation chain transfer (RAFT) polymerization and click chemistry. The alkyne‐pending copolymer of PNIPAM or PDMAEMA was obtained through RAFT copolymerization of propargyl acrylate with NIPAM or DMAEMA. Bis‐2‐azidyl‐isobutyrylamide of cystamine (AIBCy) was used as the crosslinking reagent to prepare reducibly degradable hydrogels by click chemistry. The hydrogels exhibited temperature or pH stimulus‐responsive behavior in water, with rapid response, high swelling ratio, and reproducible swelling/shrinkage cycles. The loading and release of ceftriaxone sodium proved the feasibility of the hydrogels as the stimulus‐responsive drug delivery system. Furthermore, the presence of disulfide linkage in AIBCy favored the degradation of hydrogels in the reductive environment. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3604–3612, 2010     

Thermoresponsive properties of porous poly(N‐isopropylacrylamide) hydrogels prepared in the presence of nanosized silica particles and subsequent acid treatment

Porous poly(N‐isopropylacrylamide) hydrogels were prepared by the free‐radical polymerization of its monomer and a suitable crosslinker in the presence of spherical silica particles of different sizes (74 and 1600 nm) and by the subsequent acid extraction of silica. The yields were 81–83%, and the yields were not affected by the silica content. Scanning electron microscopy observations revealed the porous structure of the hydrogels. Porous and nonporous hydrogels showed volume phase transitions from swelling states to deswelling states at approximately 30 °C, as analyzed by the ratio of the diameter of cylinder‐shaped hydrogels to that of the glass tube used for the hydrogel preparation at the corresponding temperature. Deswelling, which was analyzed by rapid changes in the temperature of the aqueous media from 20 to 40 °C, was facilitated by decreased silica particle size and increased silica content. The deswelling rate constant of the hydrogel prepared with 74‐nm silica at 10 v/v % (silica/solvent) was more than 1500 times greater than that of conventional hydrogels. Swelling was similarly analyzed through changes in the temperature from 40 to 20 °C and was independent of the pore structure. The deswelling–swelling cycle was repeatable with reasonable reproducibility. Moreover, the mechanical strength of the porous hydrogels was significantly maintained compared with that of conventional nonporous hydrogels. This method produced thermoresponsive hydrogels of suitable mechanical strength and remarkable deswelling properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4228–4235, 2002     

Double‐crosslinked reversible redox‐responsive hydrogels based on disulfide–thiol interchange

We present novel redox‐responsive hydrogels based on poly(N‐isopropylacrylamide) or poly(acrylamide), consisting of a reversible disulfide crosslinking agent N,N′‐bis(acryloyl)cystamine and a permanent crosslinking agent N,N′‐methylenebisacrylamide for microfluidic applications. The mechanism of swelling/deswelling behavior starts with the cleavage and reformation of disulfide bonds, leading to a change of crosslinking density and crosslinking points. Raman and ultraviolet‐visible spectroscopy confirm that conversion efficiency of thiol–disulfide interchange up to 99%. Rheological analysis reveals that the E modulus of hydrogel is dependent on the crosslinking density and can be repeatedly manipulated between high‐ and low‐stiffness states over at least 5 cycles without significant decrease. Kinetic studies showed that the mechanical strength of the gels changes as the redox reaction proceeds. This process is much faster than the autonomous diffusion in the hydrogel. Moreover, cooperative diffusion coefficient (D_coop) indicates that the swelling process of the hydrogel is affected by the reduction reaction. Finally, this reversibly switchable redox behavior of bulky hydrogel could be proven in microstructured hydrogel dots through short‐term photopatterning process. These hydrogel dots on glass substrates also showed the desired short response time on cyclic swelling and shrinking processes known from downsized hydrogel shapes. Such stimuli‐responsive hydrogels with redox‐sensitive crosslinkers open a new pathway in exchanging analytes for sensing and separating in microfluidics applications. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 2590–2601     

Preparation of polypyrrole‐graft‐poly(N‐isopropylacrylamide)/silver nanocomposites from pyrrolyl‐capped macromonomer by AgNO3 and their stimuli responsibility of light emission

Pyrrolyl‐capped poly(N‐isopropylacrylamide) macromonomers (Py‐PNIPAM) were prepared through reversible addition‐fragmentation‐transfer polymerization with benzyl 1‐pyrrolylcarbodithioate as chain‐transfer agent. Polymerizations of Py‐PNIPAM with/without pyrrole using AgNO₃ as oxidizing agent and dimethylforamide as solvent resulted in graft copolymers of polypyrrole‐graft‐poly(N‐isopropylacrylamide) (PPy‐g‐PNIPAM) as well as silver nanoparticles, leading to the formation of PPy‐g‐PNIPAM/silver nanocomposites. The resulting nanocomposites were soluble in water when the content of PPy was low, and when the molar ratio of Py/Py‐PNIPAM increased to 30, the resulting products became insoluble in water. The resulting nanocomposites had special optical properties because of PPy as well as the temperature‐responsible PNIPAM. The chemical structure and composition of nanocomposite were characterized by ¹H nuclear magnetic resonance spectroscopy, gel permeation chromatograms, fourier transform infrared spectroscopy, and X‐ray diffraction. Their optical properties were characterized by UV–vis and fluorescence spectroscopy. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6950–6960, 2008     

An efficient synthesis of telechelic poly (N‐isopropylacrylamides) and its application to the preparation of α,ω‐dicholesteryl and α,ω‐dipyrenyl polymers

Poly(N‐isopropylacrylamide)s (PNIPAMs) with cholesteryl or pyrenyl moieties at each chain end (CH‐PNIPAMs or Py‐PNIPAMs) were prepared via end‐group modification of α,ω‐dimercapto poly(N‐isopropylacrylamides), ranging in molecular weight from ～ 7000 to 45,000 g mol^?1 with a polydispersity index of 1.10 or lower. The telechelic thiol functionalized PNIPAMs were obtained by aminolysis of α,ω‐di(isobutylthiocarbonylthio)‐poly(N‐isopropylacrylamide)s (iBu‐PNIPAMs) obtained by reversible addition‐fragmentation chain transfer (RAFT) polymerization of N‐isopropylacrylamide in the presence of the difunctional chain transfer agent, diethylene glycol di(2‐(1‐isobutyl)sulfanylthiocarbonylsulfanyl‐2‐methyl propionate) (DEGDIM). The self‐assembly of the polymers in water was assessed by fluorescence spectroscopy, using the intrinsic emission of Py‐PNIPAM or the emission of pyrene added as a probe in aqueous solutions of CH‐PNIPAM. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 314–326, 2008     

Preparation and characterization of macroporous poly(N‐isopropylacrylamide) hydrogels for the controlled release of proteins

Macroporous, temperature‐sensitive poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels were synthesized with poly(ethylene glycol)s (PEGs; molecular weight = 2000–6000) as the pore‐forming agents. The influence of the molecular weight and PEG content on the responsive kinetics of these macroporous hydrogels was investigated. The PEG‐modified PNIPAAm hydrogels were characterized by the swelling ratio, deswelling–reswelling kinetics, Fourier transform infrared, and differential scanning calorimetry. The morphology of these hydrogels was analyzed with scanning electron microscopy. The prepared macroporous hydrogels exhibited some unique properties in comparison with the gels with low molecular weight PEGs (molecular weight < 2000) as the pore‐forming agents. In addition, a preliminary study on the controlled release of bovine serum albumin from these macroporous hydrogels was carried out. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 152–159, 2003     

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     

Poly(N‐isopropylacrylamide)‐based comb‐type grafted hydrogel with rapid response to blood glucose concentration change at physiological temperature

A new type of glucose‐responsive hydrogel with rapid response to blood glucose concentration change at physiological temperature has been successfully developed. The polymeric hydrogel contains phenylboronic acid (PBA) groups as glucose sensors and thermo‐responsive poly (N‐isopropylacrylamide) (PNIPAM) groups as actuators. The response rate of the hydrogel to environmental glucose concentration change was significantly enhanced by introducing grafted poly(N‐isopropylacrylamide‐co‐3‐acrylamidophenylboronic acid) [poly(NIPAM‐co‐AAPBA)] side chains onto crosslinked poly(NIPAM‐co‐AAPBA) networks for the first time. The synthesized comb‐type grafted poly(NIPAM‐co‐AAPBA) hydrogels showed satisfactory equilibrium glucose‐responsive properties, and exhibited much faster response rate to glucose concentration change than normal type crosslinked poly(NIPAM‐co‐AAPBA) hydrogels at physiological temperature. Such glucose‐responsive hydrogels with rapid response rate are highly attractive in the fields of developing glucose‐responsive sensors and self‐regulated drug delivery systems. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

Aqueous RAFT polymerization of N‐isopropylacrylamide‐mediated with hydrophilic macro‐RAFT agent: Homogeneous or heterogeneous polymerization?

Aqueous RAFT polymerization of N‐isopropylacrylamide (NIPAM) mediated with hydrophilic macro‐RAFT agent is generally used to prepare poly(N‐isopropylacrylamide) (PNIPAM)‐based block copolymer. Because of the phase transition temperature of the block copolymer in water being dependent on the chain length of the PNIPAM block, the aqueous RAFT polymerization is much more complex than expected. Herein, the aqueous RAFT polymerization of NIPAM in the presence of the hydrophilic macro‐RAFT agent of poly(dimethylacrylamide) trithiocarbonate is studied and compared with the homogeneous solution RAFT polymerization. This aqueous RAFT polymerization leads to the well‐defined poly(dimethylacrylamide)‐b‐poly(N‐isopropylacrylamide)‐b‐poly(dimethylacrylamide) (PDMA‐b‐PNIPAM‐b‐PDMA) triblock copolymer. It is found, when the triblock copolymer contains a short PNIPAM block, the aqueous RAFT polymerization undergoes just like the homogeneous one; whereas when the triblock copolymer contains a long PNIPAM block, both the initial homogeneous polymerization and the subsequent dispersion polymerization are involved and the two‐stage ln([M]_o/[M])‐time plots are indicated. The reason that the PNIPAM chain length greatly affects the aqueous RAFT polymerization is discussed. The present study is anticipated to be helpful to understand the chain extension of thermoresponsive block copolymer during aqueous RAFT polymerization. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Synthesis and characterization of PNIPAM‐b‐(PEA‐g‐PDEA) double hydrophilic graft copolymer

A series of well‐defined double hydrophilic graft copolymers, consisting of poly(N‐isopropylacrylamide)‐b‐poly(ethyl acrylate) (PNIPAM‐b‐PEA) backbone and poly(2‐(diethylamino)ethyl methacrylate) (PDEA) side chains, were synthesized by successive atom transfer radical polymerization (ATRP). The backbone was firstly prepared by sequential ATRP of N‐isopropylacrylamide and 2‐hydroxyethyl acrylate at 25 °C using CuCl/tris(2‐(dimethylamino)ethyl)amine as catalytic system. The obtained diblock copolymer was transformed into macroinitiator by reacting with 2‐chloropropionyl chloride. Next, grafting‐from strategy was employed for the synthesis of poly(N‐isopropylacrylamide)‐b‐[poly(ethyl acrylate)‐g‐poly(2‐(diethylamino)ethyl methacrylate)] (PNIPAM‐b‐(PEA‐g‐PDEA)) double hydrophilic graft copolymer. ATRP of 2‐(diethylamino)ethyl methacrylate was initiated by the macroinitiator at 40 °C using CuCl/hexamethyldiethylenetriamine as catalytic system. The molecular weight distributions of double hydrophilic graft copolymers kept narrow. Thermo‐ and pH‐responsive micellization behaviors were investigated by fluorescence spectroscopy, ¹H NMR, dynamic light scattering, and transmission electron microscopy. Unimolecular micelles with PNIPAM‐core formed in acidic environment (pH = 2) with elevated temperature (≥32 °C); whereas, the aggregates turned into vesicles in basic surroundings (pH ≥ 7.2) at room temperature. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5638–5651, 2008     

Effect of the crosslinking level on the properties of temperature‐sensitive poly(N‐isopropylacrylamide) hydrogels

In this study, the effect of the level of crosslinking on the properties of poly(N‐isopropylacrylamide) (PNIPAAm) hydrogels was investigated in terms of their lower critical solution temperature (LCST), interior morphology, equilibrium swelling, and deswelling and swelling kinetics. The thermal analysis showed that PNIPAAm hydrogels, having a wide range of crosslinking levels, exhibited almost the same LCSTs, and this was different from what the conventional theory would have predicted. Scanning electron micrographs revealed that the interior network structure of the PNIPAAm matrix became more porous with an increase in the level of crosslinking. This more porous matrix provided numerous water channels for water diffusion in or out of the matrix and, therefore, an improved response rate to the external temperature changes during the deswelling process and the swelling process. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 582–593, 2003     

Newly designed hydrogel with both sensitive thermoresponse and biodegradability

The synthesis and characterization of thermoresponsive hydrogels on the basis of N‐isopropylacrylamide (IPAAm) copolymers crosslinked with biodegradable poly(amino acids) are described. This hydrogel was prepared with two kinds of reactive IPAAm‐based copolymers containing poly(amino acids) as the side‐chain groups and activated ester groups. We introduced the graft chains by decarboxylation polymerization of amino acid N‐carboxyanhydrides initiated from lateral amino groups in the PIPAAm copolymer. The hydrogels easily crosslinked with degradable poly(amino acid) chains by only mixing the copolymer aqueous solutions. The gelling method in this study would provide some of the following innovative features: (1) no necessary removal of unreacted monomers and so forth, (2) simpler loading of drugs into the hydrogels (only mixing when gelling), and (3) easier insertion into the body. On the basis of the swelling ratio measurement of the hydrogel, large volume changes dependent on temperature changes were observed. Moreover, the enzymatic temperature‐dependent degradation was confirmed. The results suggested that these hydrogels could be used for an injectable or implantable matrix of temperature‐modulated drug release. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 779–787, 2003     

An H‐shaped polymer bonding β‐cyclodextrin at branch points: Synthesis and influences of attached β‐cyclodextrins on physical properties

We report on the synthesis of an H‐shaped polymer bonding β‐cyclodextrin (β‐CD) at branch points and influences of attached β‐CD on physical properties. First, a poly(ethylene glycol)(PEG)‐based functional macroinitiator bearing two azidos and four chlorines at chain‐ends (PEG‐2N₃(‐4Cl)) was prepared via terminal modification reactions. Then, PEG‐2N₃(‐4Cl) was applied to initiate the atom transfer radical polymerization of N‐isopropylacrylamide, leading to the synthesis of an H‐shaped block polymer with PEG as the central chain and poly(N‐isopropylacrylamide) (PNIPAM) as side‐arms (PEG‐2N₃(‐4PNIPAM)). Azido groups were at the branch points of the polymer. Finally, the click reaction between PEG‐2N₃(‐4PNIPAM) and alkynyl monosubstituted β‐cyclodextrin (β‐CD) afforded another H‐shaped polymer with two β‐CDs bonding at the polymer branch points (PEG‐2CD(‐4PNIPAM)). The glass transition temperature (T_g) and lower critical solution temperature (LCST) of the H‐shaped polymer increased after the attachment of β‐CD. The self‐assembly and thermal responsive behaviors, as well as the encapsulation behaviors of PEG‐2CD(‐4PNIPAM) were also altered. When temperature was below the LCSTs, PEG‐2N₃(‐2PNIPAM) dissolved in water molecularly, whereas PEG‐2CD(‐4PNIPAM) could self‐assemble into nano‐sized micelles. After the LCST transitions, PEG‐2N₃(‐4PNIPAM) aggregated into micron‐sized unstable particles, whereas PEG‐2CD(‐4PNIPAM) transformed into PNIPAM‐cored nanomicelles. Besides, PEG‐2CD(‐4PNIPAM) can encapsulate doxorubicin below its LCST due to the formation of micelles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013