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     

Preparation and properties of poly(N‐isopropylacrylamide)/poly(N‐isopropylacrylamide) interpenetrating polymer networks for drug delivery

A novel poly(N‐isopropylacrylamide) (PNIPA)/PNIPA interpenetrating polymer network (IPN) was synthesized and characterized. In comparison with conventional PNIPA hydrogels, the shrinking rate of the IPN hydrogel increased when gels, swollen at 20 °C, were immersed in 50 °C water. The phase‐transition temperature of the IPN gel remained unchangeable because of the same chemical constituent in the PNIPA gel. The reswelling kinetics were slower than those of the PNIPA hydrogel because of the higher crosslinking density of the IPN hydrogel. The IPN hydrogel had better mechanical strength because of its higher crosslinking density and polymer volume fraction. The release behavior of 5‐fluorouracil (5‐Fu) from the IPN hydrogel showed that, at a lower temperature, the release of 5‐Fu was controlled by the diffusion of water molecules in the gel network. At a higher temperature, 5‐Fu inside the gel could not diffuse into the medium after a burst release caused by the release of the drug on the surface of the gel. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1249–1254, 2004     

Investigation of swelling,drug release and diffusion behaviors of poly(N‐isopropylacrylamide)/poly (N‐vinylpyrrolidone) full‐IPN hydrogels

The synthesis of sequential full interpenetrating polymer networks (IPNs) based on poly (N‐isopropylacrylamide) (PNIPAAm) and negatively charged poly(N‐vinyl‐2‐pyrrolidone) (PNVP) was described and their swelling, drug release, and diffusion studies were investigated. PNIPAAm was used as a host network. According to swelling experiments, IPNs gave relatively lower swelling ratios compared to PNIPAAm hydrogel due to the higher cross‐linking density. Lidocaine (LD) was used as a model drug for the investigation of drug release behavior of IPNs. LD uptake of the IPNs were found to increase from 24 to 166 (mg LD / g dry gel) with increasing amount of PNIPAAm and AMPS contents in the IPN structure. It was observed that the specific interaction between drug and AMPS co‐monomer influenced the drug release profile. In the diffusion transport mechanism study in water, the results indicated that the swelling exponents n for all IPNs are in the range from 0.50 to 0.72. This implies that the swelling transport mechanism was transferred from Fickian to non‐Fickian transport, with increasing AMPS content and NIPAAm character in the IPN structure. In addition, diffusion of LD within the IPNs showed similar trend. The incorporation of AMPS leads to an increase in electrostatic interaction between charge sites on carboxylate ions and cationic LD molecules. Therefore, the highest diffusion coefficient (D) of drug was found for IPN2 sample. Copyright © 2007 John Wiley & Sons, Ltd.     

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     

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.     

Molecular Characteristics of Poly(N‐isopropylacrylamide) Separated from Nanocomposite Gels by Removal of Clay from the Polymer/Clay Network

The extraordinary mechanical and swelling/deswelling properties of nanocomposite (NC) gels are attributed to their unique organic (polymer)/inorganic (clay) network structure. In this study, poly(N‐isopropylacrylamide) (PNIPA) was successfully separated from an NC gel network by decomposing the clay (hectorite) using hydrofluoric acid (HF). A very low HF concentration (0.2 wt.‐%) was adequate for the decomposition of the clay without causing any damage to PNIPA. The separated PNIPA had a high (=5.5 × 10⁶ g · mol⁻¹). Also, was almost constant regardless of the clay concentration (C_clay = 1–25 × 10⁻² mol · l⁻¹), even though the properties of the NC gel varied widely over this C_clay range. Comparisons of NC gels, PNIPA, and SiO₂‐NC gels indicated that the clay platelets specifically play an important role in NC gels.

     

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     

Associative block copolymers comprising poly(N‐isopropylacrylamide) and poly(ethylene oxide) end‐functionalized with a fluorophilic or hydrophilic group. Synthesis and aqueous solution properties

A series of block copolymers comprising poly(N‐isopropylacrylamide) (PNIPAM) and poly(ethylene oxide) (PEO) end‐functionalized with a quaternary ammonium group (R_Q) was synthesized by free‐radical polymerization of N‐isopropylacrylamide with well‐defined R_QPEO macroazoinitiators. The radical termination occurred mainly by disproportionation, as confirmed by combining the data from size exclusion chromatography (SEC) and rheology measurements. The copolymers denoted R_QE_xN_y differ in type of the terminal group [F_Q = C₈F₁₇(CH₃)₂N⁺ or M_Q = (CH₃)₃N⁺] and in the length of the PEO (E_x; x = 4, 6, or 10 K) and PNIPAM (N_y; y = 7 or 17–19 K) blocks. The type of the terminal group determined the behavior of the block copolymers in the dilute and semidilute regime. Self‐assembled species formed by both F_Q and M_Q modified block copolymers were detected by static light scattering measurements at 25 °C and above the lower critical solution temperature (LCST). The LCST of the block copolymers depended on the type of the R_Q group and the length of the blocks. F_Q‐modified copolymers form elastic gels below and above the LCST. It was inferred that the F_Q groups and the PNIPAM blocks form segregated microdomains that serve as junctions to maintain a viscoelastic network. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5736–5744, 2004     

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     

Investigation of drug release from thermo‐ and pH‐sensitive poly(N‐isopropylacrylamide/itaconic acid) copolymeric hydrogels

N‐Isopropylacrylamide/itaconic acid copolymeric hydrogels were prepared by irradiation of the ternary mixtures of N‐isopropylacrylamide/itaconic acid/water by γ‐rays at ambient temperature. The dependence of swelling properties and phase transitions on the comonomer concentration and temperature were investigated. The hydrogels showed both temperature and pH responses. The effect of comonomer concentration on the uptake and release behavior of the hydrogels was studied. Methylene blue (MB) was used as a model drug for the investigation of drug uptake and release behavior of the hydrogels. The release studies showed that the basic parameters affecting the drug release behavior of the hydrogels were pH and temperature of the solution. Copyright © 2004 John Wiley & Sons, Ltd.     

β‐Cyclodextrin hydrogel incorporating hydrophobically modified poly(N‐isopropylacrylamide) for a temperature‐dependent release

Hydrogels exhibiting a temperature‐dependent release were prepared by incorporating hydrophobically modified poly(N‐isopropylacrylamide) (HmPNIPAM) into β‐cyclodextrin hydrogels (β‐CD hydrogels). The specific loading of HmPNIPAM was about 0.0069 g HmPNIPAM/g β‐CD hydrogels. The incorporation of the polymer was qualitatively conformed by FT‐IR spectroscopy and SEM. The percent release of blue dextran in 24 hr at 20°C (about 77%) was markedly higher than those obtained at 35°C and 45°C (about 53 and 55%, respectively). At the higher temperatures, the volume of the hydrogel could decrease upon the thermal contraction of HmPNIPAM, leading to a smaller mesh and a suppressed release. In fact, the swelling ratio in 24 hr at 35°C and 45°C (about 396% and 405%, respectively) was obviously lower than that obtained at 20°C (about 465%). Copyright © 2011 John Wiley & Sons, Ltd.     

Rapid and controlled deswelling of porous poly(N‐isopropylacrylamide) hydrogels prepared by the templating of interpenetrated nanoporous silica particles

Free radical polymerization of N‐isopropylacrylamide (NIPAAm) and crosslinker solutions, which were fulfilled in silica particles with an interpenetrated and nanometer‐sized porous structure (a diameter of 3 mm and mean pore sizes of 15, 30, and 50 nm), fabricated hybrids of organic hydrogels and inorganic silica. Differential scanning calorimetric analyses of the hybrids revealed that silica components affected the thermoresponsive properties of polyNIPAAm hydrogels. Porous polyNIPAAm hydrogels were prepared by the subsequent acid treatment of the hybrids to remove silica. Transmission Fourier transformed infrared spectra indicated the selective extraction of silica. Scanning electron microscopic observation of the hydrogels confirmed the porous structure. The deswelling rate of porous hydrogels was 7 times larger than that of conventional hydrogels and increased with increasing the pore size of silica used. However, the swelling was not affected by the pore formation. The thermoresponsiveness of porous polyNIPAAm hydrogels could be regulated by the pore size. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3542–3547, 2002     

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     

Living anionic polymerization of N‐methoxymethyl‐N‐isopropylacrylamide: Synthesis of well‐defined poly(N‐isopropylacrylamide) having various stereoregularity

Anionic polymerization of N‐methoxymethyl‐N‐isopropylacrylamide ( 1 ) was carried out with 1,1‐diphenyl‐3‐methylpentyllithium and diphenylmethyllithium, ‐potassium, and ‐cesium in THF at ?78 °C for 2 h in the presence of Et₂Zn. The poly( 1 )s were quantitatively obtained and possessed the predicted molecular weights based on the feed molar ratios between monomer to initiators and narrow molecular weight distributions (M_w/M_n = 1.1). The living character of propagating carbanion of poly( 1 ) either at 0 or ?78 °C was confirmed by the quantitative efficiency of the sequential block copolymerization using N,N‐diethylacrylamide as a second monomer. The methoxymethyl group of the resulting poly( 1 ) was completely removed to give a well‐defined poly(N‐isopropylacrylamide), poly(NIPAM), via the acidic hydrolysis. The racemo diad contents in the poly(NIPAM)s could be widely changed from 15 to 83% by choosing the initiator systems for 1 . The poly(NIPAM)s obtained with Li⁺/Et₂Zn initiator system possessed syndiotactic‐rich configurations (r = 75–83%), while either atactic (r = 50%) or isotactic poly(NIPAM) (r = 15–22%) was generated with K⁺/Et₂Zn or Li⁺/LiCl initiator system, respectively. Atactic and syndiotactic poly(NIPAM)s (42 < r < 83%) were water‐soluble, whereas isotactic‐rich one (r < 31%) was insoluble in water. The cloud points of the aqueous solution of poly(NIPAM)s increased from 32 to 37 °C with the r‐contents. These indicated the significant effect of stereoregularity of the poly(NIPAM) on the water‐solubility and the cloud point in water © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4832–4845, 2006     

Molecular Dynamics Investigation of the Thermo‐Responsive Polymer Poly(N‐isopropylacrylamide)

Using molecular dynamics simulations with an OPLS force field, the lower critical solution temperature (LCST) of single‐ and multiple‐chain PNIPAM solutions in water is investigated. The sample containing ten polymer chains shows a sudden drop in size and volume at 305 K. Such an effect is absent in the single‐chain system. Large fluctuations of the physical properties of a short single‐chain prevent any clear detection of the LCST for the chosen model system, at least on the time scale of 200 ns. The results provide evidence that a critical number of PNIPAM monomer units must be present in the simulated system before MD simulations are capable to detect conformational changes unambiguously.

     

A novel pH‐ and thermo‐sensitive PVP/CMC semi‐IPN hydrogel: Swelling,phase behavior,and drug release study

Poly(N‐vinyl‐pyrrolidone) (PVP) hydrogel has been considered as a very interesting and promising thermosensitive material. The most vital shortcoming of PVP hydrogel as thermosensitive material is that it does not exhibit thermosensitivity under usual conditions. In this work, semi‐interpenetrating polymer network (semi‐IPN) hydrogels based on PVP and carboxymethylcellulose (CMC) were prepared. The volume phase transition temperature (VPTT) of the hydrogels was determined by swelling behavior and differential scanning calorimetry (DSC). The results showed that the VPTT was significantly dependent on CMC content and the pH of the swelling medium. The amount of CMC in the semi‐IPN hydrogels was 0.050, 0.075, and 0.100 g, the VPTT in buffer solution of pH 1.2 was 29.9 °C, 27.5 °C and 24.5 °C, respectively. In addition, the VPTT occurred in buffer solution of pH 1.2, but did not appear in alkaline medium. Bovine serum albumin (BSA) as a model drug was loaded and the in vitro release studies were carried out in different buffer solutions and at different temperatures. The results of this study suggest that PVP/CMC semi‐IPN hydrogels could serve as potential candidates for protein drug delivery in the intestine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1749–1756, 2010     

Novel temperature‐ and pH‐responsive graft copolymers composed of poly(L‐glutamic acid) and poly(N‐isopropylacrylamide)

A series of novel temperature‐ and pH‐responsive graft copolymers, poly(L ‐glutamic acid)‐g‐poly(N‐isopropylacrylamide), were synthesized by coupling amino‐semitelechelic poly(N‐isopropylacrylamide) with N‐hydroxysuccinimide‐activated poly(L ‐glutamic acid). The graft copolymers and their precursors were characterized, by ESI‐FTICR Mass Spectrum, intrinsic viscosity measurements and proton nuclear magnetic resonance (¹H NMR). The phase‐transition and aggregation behaviors of the graft copolymers in aqueous solutions were investigated by the turbidity measurements and dynamic laser scattering. The solution behavior of the copolymers showed dependence on both temperature and pH. The cloud point (CP) of the copolymer solution at pH 5.0–7.4 was slightly higher than that of the solution of the PNIPAM homopolymer because of the hydrophilic nature of the poly(glutamic acid) (PGA) backbone. The CP markedly decreased when the pH was lowered from 5 to 4.2, caused by the decrease in hydrophilicity of the PGA backbone. At a temperature above the lower critical solution temperature of the PNIPAM chain, the copolymers formed amphiphilic core‐shell aggregates at pH 4.5–7.4 and the particle size was reduced with decreasing pH. In contrast, larger hydrophobic aggregates were formed at pH 4.2. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4140–4150, 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     

Recent development of temperature‐responsive cell culture surface using poly(N‐isopropylacrylamide)

Poly(N‐isopropylacrylamide) (PIPAAm), which is a well‐known temperature‐responsive polymer, is modified on substrates by various methods. At 37 °C, PIPAAm modified surface is hydrophobic and allows cells to adhere to and proliferate on the surface. By reducing temperature below the lower critical solution temperature of PIPAAm, the surface turns to hydrophilic and allows cells to detach themselves from the surface spontaneously. With this technology, cell sheet engineering is established several years ago. This review focuses on the preparations and characteristics of PIPAAm‐modified surfaces, and discusses the effect of surface properties on cell adhesion and deadhesion. In addition, the recent improvement of PIPAAm‐modified surfaces for cell culture and the clinical applications of cell sheets harvested from the surfaces are also mentioned. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 917–926