A stimulus-responsive magnetic nanoparticle drug carrier: magnetite encapsulated by chitosan-grafted-copolymer

We describe a magnetic nanoparticle drug carrier for controlled drug release that responds to the change in external temperature or pH, with characteristics of longer circulation time and reduced side effects. The novel nanocarrier is characterized by a functionalized magnetite (Fe(3)O(4)) core that is conjugated with drug via acid-labile hydrazone-bond and encapsulated by the thermosensitive smart polymer, chitosan-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) [chitosan-g-poly(NIPAAm-co-DMAAm)]. The chitosan-g-poly(NIPAAm-co-DMAAm) smart polymer exhibits a lower critical solution temperature (LCST) of approximately 38 degrees C, signifying phase transition behavior of the smart polymer and enabling its use for triggering on-off mechanisms. The drug release response was appreciably low at a temperature less than the LCST as compared with a temperature above the LCST. In each case, there was an initial rapid drug release, followed by a controlled released in the second stage, especially in a mild acidic buffer solution of pH 5.3. We believe that the drug release occurs via a collapse of the encapsulated thermosensitive polymer and cleavage of the acid-labile hydrazone linkage.     

Poly(vinyl alcohol) microspheres with pH- and thermosensitive properties as temperature-controlled drug delivery

One of the most important inconveniences of the pH- and temperature-sensitive hydrogels is the loss of thermosensitivity when relatively large amounts of a pH-sensitive monomer are co-polymerized with N-isopropylacrylamide (NIPAAm). In order to overcome this drawback, we propose here a method to prepare thermosensitive poly(vinyl alcohol) (PVA) microspheres with a higher content of carboxylic groups that preserve thermosensitive properties. Moreover, PVA possesses excellent mechanical properties, biocompatibility and non-toxicity. PVA microspheres were obtained by suspension cross-linking of an acidified aqueous solution of the polymer with glutaraldehyde. Poly(N-isopropylacrylamide-co-N-hydroxymethyl acrylamide) (poly(NIPAAm-co-HMAAm)), designed to have a lower critical solution temperature (LCST) corresponding to that of the human body, was grafted onto PVA microspheres in order to confer them with thermosensitivity. Then, the pH-sensitive functional groups (COOH) were introduced by reaction between the un-grafted OH groups of PVA and succinic anhydride. The pH- and temperature-sensitive PVA microspheres display a sharp volume transition under physiological conditions around the LCST of the linear polymer. The microspheres possess good drug-loading capacity without losing their thermosensitive properties. Under simulated physiological conditions, the release of drugs is controlled by temperature.     

The effect of extensible PEG tethers on shielding between grafted thermo-responsive polymer chains and integrin-RGD binding

The affinity control of integrin-RGD (Arg-Gly-Asp) binding by a thermal "on-off" switch has been achieved using newly designed surfaces presenting grafted temperature-responsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide) copolymers functionalized with synthetic peptides. The prepared surface was designed to expose the tethered peptides available for cell binding at active "on" state above the lower critical solution temperature (LCST). The fully extended chains, on the other hand, masked the peptides completely and the cells started to detach from the surfaces at inactive "off" sate below the LCST. This paper elucidates the shielding effect of the grafted polymer chains on the dissociation of integrin-RGD binding below the LCST. To assess the ability of the polymer-shielding, extensible poly(ethylene glycol) (PEG) tethers were introduced between peptides and the grafted polymers. PEG chains allow peptides to be tethered to surfaces via functional PEG end-groups, leading to active "on" state even below the LCST. The time required to release cells from the surface was found to be longer when peptides were coupled to an extensible tether ends, suggesting that the surfaces can engender cell attachment through adhesive moieties covalently bound to the free ends of PEG chains. These results indicate that architectural changes on the nanometer length scale are crucial for controlling integrin-RGD binding and one of the main factors causing cell detachment is the shielding effect of the grafted polymer chains.     

Polymer–Clay Nanocomposite Microspheres and their Thermosensitive Characteristics

Polymer–clay nanocomposite (P‐NC) microspheres are synthesized through in situ free‐radical polymerization in aqueous media without the use of surfactants. Uniform aqueous dispersions of P‐NC microspheres without flocculation/precipitation are obtained for five types of (co)polymers with different hydrophilic/hydrophobic natures, in which the exfoliated clay platelets play an important role as crosslinkers and stabilizers in water. The sol–gel boundary, transparency of the aqueous dispersion, microsphere particle size, etc. vary depending on the compositions and polymerization methods. Aqueous dispersions of P‐NC microspheres with a well‐defined lower critical solution temperature (LCST)‐type thermosensitive transition are obtained by using N‐isopropylacrylamide (NIPA), 2‐methoxyethylacrylate (MEA), and N,N‐dimethylacrylamide (DMAA) as the (co)monomers. In the case of P‐NC microspheres consisting of inorganic clay and NIPA‐DMAA or MEA‐DMAA copolymers, the LCST is controlled over a wide range, particularly depending on the DMAA content. The P‐NC microspheres applied within double‐layer glass plates are examined as reversible and efficient thermosensitive optical shutters.

     

Preparation and characterization of pH- and temperature-sensitive pullulan microspheres for controlled release of drugs

Most part of pH- and temperature-sensitive microspheres used for the controlled delivery of drugs are not biodegradable. Therefore, the aim of this work is to prepare pH- and temperature-sensitive microspheres from biodegradable and biocompatible natural polymers. Pullulan microspheres were prepared by suspension cross-linking with epichlorohydrin of an aqueous solution of the polymer. In order to confer them temperature sensitivity, poly(N-isopropylacrylamide-co-acrylamide) was grafted onto pullulan microspheres. Then, the pH-sensitive units (-COOH) were introduced by reaction between the remaining -OH groups of the pullulan with succinic anhydride. The grafted pullulan microspheres are more hydrophilic than pullulan microspheres, their swelling degree as well as water regain increase significantly. The thermo-sensitivity of the carboxylated microspheres depends to the number and the ionization form (-COOH/-COO(-)) of carboxylic groups. At a low exchange capacity (0.35 meq/g), microspheres are thermo-sensitive both in the protonated and deprotonated form of -COOH groups. At a higher exchange capacity (2.25 meq/g), microspheres are almost unswellable in the protonated form and swell extensively in the ionized form (up to 28 times than their dried form) loosing in a great extent the thermo-sensitive properties. In isotonic phosphate buffer pH=7.4, both thermo-sensitive and pH/thermo-sensitive microspheres possess a phase transition temperature close to that of the human body temperature. Loading and release profiles of lysozyme, taken as a molecular model system, were investigated.     

Effect of molecular weight and polydispersity on kinetics of dissolution and release from ph/temperature-sensitive polymers

N-isopropylacrylamide (NIPAAm) polymers exhibit a lower critical solution temperature (LCST). Aqueous solutions of these polymers are soluble below their LCST and precipitate above their LCST. The LCST is dependent on pH for polymers with ionizable groups because of a change in hydrophilicity with ionization and electrostatic repulsion that cause a shift in the LCST. We have designed a novel polymeric delivery system that utilizes linear, pH/temperature-sensitive terpolymers of NIPAAm, butyl methacrylate (BMA) and acrylic acid (AA). This system allows the aqueous loading of drugs in polymeric beads with high loading efficiency while preserving the bioactivity of the protein drug. Furthermore, the unique properties of the pH/temperature-sensitive polymeric bead make it a potential system for oral drug delivery of peptide and protein drugs to different regions of the intestinal tract. This study aims at investigating the effect of polydispersity and molecular weight (MW) of terpolymers of poly(NIPAAm-co-BMA-co-AA) with feed mol ratio of NIPAAm/BMA/AA 85/5/10 on the polymer dissolution rate and on the release kinetics of a model protein, namely insulin. Varying the weight average MW (Mw) and polydispersity of the polymer modulated the polymer dissolution rate and the release rate of insulin from pH/temperature-sensitive polymeric beads. An increase in the polydispersity of the polymer through the addition of high MW polymer chains caused a decrease in the release rate of insulin and in the polymer dissolution rate. High MW polymer chains impose a certain degree of interaction between polymer chains due to chain entanglement. There is a limiting value of MW above which chain entanglement has no effect on drug release rate.     

Hydrophilic–Hydrophobic‐Transition‐Triggered Thermosensitive Macroscopic Gel Assembly

Two kinds of poly(N‐isopropylacrylamide) (PNIPAAm)‐based hydrogels containing β‐cyclodextrin (β‐CD) (host gel) and benzyl (guest gel) groups, respectively, are designed and prepared. When mixing the host and guest gels together, due to the presence of the host–guest interaction between the β‐CD and benzyl groups, a combined hydrogel can be formed at a temperature below the lower critical solution temperature (LCST) via macroscopic self‐assembly. When heating this self‐assembling system to a temperature above the LCST, the aggregation of the hydrophobic PNIPAAm‐based chains pull the β‐CD and benzyl groups to separate them from each other, leading to the disassociation of the combined hydrogel. Because of the transition from hydrophobic aggregated PNIPAAm‐based chains to hydrophilic extended ones as the temperature decreases to a value below LCST, the combined hydrogel can re‐form via macroscopic self‐assembly between the host and guest gels. The concept of hydrophilic–hydrophobic transition‐triggered thermosensitive macroscopic self‐assembly can be extended to develop many other stimuli‐responsive materials.

     

Self-assembled, fluorescent polymeric micelles of a graft copolymer containing carbazole for thermo-controlled drug delivery in vitro

A novel thermosensitive amphiphilic graft copolymer PNIPAAm-g-PCbzEA appending carbazole group was successfully designed and synthesized by the free radical copolymerization of N-isopropylacrylamide with hydrophobic precursor polymers of vinyl-functionalized poly(2-(N-carbazolyl)ethyl acrylate) (PCbzEA) in DMF. The PNIPAAm-g-PCbzEA copolymer was characterized by FTIR, (1)H NMR, GPC analysis, UV-vis spectroscopy and fluorescence spectroscopy. The TEM observation shows that the graft copolymer may self-assemble into polymeric micelles exhibiting a nanospheric morphology within a narrow size range of 30-60 nm in aqueous solution. From the (1)H NMR and FTIR analysis, the polymer micelles are composed of hydrophobic PCbzEA segments as the cores and the hydrophilic PNIPAAm segements as outer shells. The resulting micelles exhibited the temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.9 mg/L in water. In the study of drug release, an "on-off" drug release profile was found in response to stepwise temperature changes between 20 and 40 degrees C. The cytotoxicity assays for vero cells shows good biocompatibility of the graft copolymer in vitro.     

Novel thermosensitive calcium alginate microspheres: Physico-chemical characterization and delivery properties

The system described in this paper was obtained by soaking calcium alginate (CaAlg) microspheres in a water solution of poly-[(3-acrylamidopropyl)-trimethylammonium chloride-b-N-isopropylacrylamide] [poly(AMPTMA-b-NIPAAM)], a new block co-polymer recently synthesized by atom transfer radical polymerization (ATRP). The block co-polymer is characterized by a lower critical solution temperature (LCST) of 41 °C in aqueous 0.1 M NaCl solution, and can be anchored on the CaAlg microspheres by means of polyion interactions. Polycations (permanently positively charged blocks) and polyanions (free alginate carboxylic groups) interact, leading to microspheres with thermosensitive properties. As an effect of interaction with the microspheres the LCST of the co-polymer is lowered to 36–38 °C. In this temperature range a colloidal water suspension of the microspheres collapses, forming macroscopic aggregates. The new system shows, at human body temperature, an improved ability to carry and deliver both hydrophobic and hydrophilic molecules in comparison with unmodified CaAlg microspheres. The release properties of the microspheres loaded with different model drugs can be appropriately modulated by the amount of the poly(AMPTMA-b-NIPAAM). Furthermore, the microspheres show the interesting capability of retaining the activity of a loaded enzyme (horseradish peroxidase), used as a model protein. The results obtained indicate that the proposed drug delivery system may be suitable for drug depot applications.     

Thermo‐Responsive Copolymers Based on Poly(N‐isopropylacrylamide) and Poly[2‐(methacryloyloxy)ethyl phosphorylcholine]: Light Scattering and Microscopy Experiments

Aqueous self‐assembly of thermosensitive triblock copolymers based on poly(N‐isopropylacrylamide) and poly[2‐(methacryloyloxy)ethyl phosphorylcholine] (PNIPAM_m–PMPC_n–PNIPAM_m and PNIPAM_m–PMPC_n–S–S–PMPC_n–PNIPAM_m) were studied using light scattering (SLS and DLS), TEM and fluorescence experiments. These techniques were used to investigate the morphological transition as a function of the temperature, below and above the LCST of the PNIPAM, at various triblock copolymer concentrations ranging from dilute to semi‐dilute regimes. Below the LCST and at low concentrations, aqueous solutions show micellar behavior, while above the LCST self‐assembly leading to large nanoparticles stabilized with PMPC chains. Such behavior is the onset of a gel‐like phase transition observed at higher concentrations.

     

An intelligent multicompartmental system based on thermo-sensitive starch microspheres for temperature-controlled release of drugs

An original multicompartmental drug delivery system based on encapsulation of “intelligent” starch microspheres was designed and developed. Starch microspheres with thermo-responsive properties and possessing strong anionic functional groups (-SO₃H), capable to bind electrostatically drugs, has been prepared. Firstly, the thermo-responsive units based on copolymer of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) with a lower critical solution temperature around 36oC, were grafted on preformed starch microspheres. Secondly, the strong anionic groups (-SO₃H) were introduced by sequential grafting of 2-acrylamido-2-methyl-1-propanesulfonic acid on the remaining—OH groups of starch. The thermo-sensitive microspheres with sulfonic groups display a sharp phase transition around the human body temperature. They were complexed with the positively-charged metoclopramide (low molecular weight model drug) and then encapsulated in cellulose acetate butyrate microcapsules by an oil-in-water solvent evaporation method. The swelling and diffusion of encapsulated microspheres to the aqueous continuous phase is avoided because the temperature of aqueous phase is higher than volume phase transition temperature (VPTT) of microspheres. This multicompartmental device could develop the background of “smart” implantable drug delivery system for persons that work in dangerous cold places (builders, climbers). When the temperature of the human body decreases below the normal temperature (the threshold temperature could be tuned), the encapsulated microspheres swell extensively in contact with physiological fluids, break the microcapsules and a large amount of bioactive compounds is released, keeping the activity of the vital organs. In normal physiological conditions (above LCST), the microspheres slightly swell, fill up the microcavities of microcapsules, but do not break them and release the drug in microcompartments. These microcompartments become microreservoirs with bioactive compounds and release it with a very low rate maintaining the necessary concentration for a sustained activity of the body.     

Effect of modification manner on the photodynamic antitumor activity of C60 modified with pullulan

To design a novel cytospecific photosensitizer for photodynamic antitumor therapy, a fullerene (C(60)) was chemically modified with pullulan, a water-soluble polysaccharide with a high affinity for asialoglycoprotein receptors (ASGPRs). The effect of the molecular weight of pullulan and the modification manner to C(60) on the photodynamic antitumor activity of C(60) modified with pullulan was evaluated. In this study, two modification manners were selected. First, ethylene diamine was chemically introduced to the hydroxyl groups of pullulan with different molecular weights. Then, C(60) was coupled to pullulan through the amino groups introduced (pendant type). Second, ethylene diamine was introduced to the terminal aldehyde groups of pullulan by a reductive amination reaction, and then the pullulan with the terminal amino groups was coupled to C(60) (terminal type). Irrespective of the pullulan molecular and the modification manner, the C(60)-pullulan conjugates exhibited a similar ability to generate superoxide anions upon light irradiation. Comparing the C(60)-pullulan conjugates of pendant and terminal types, a high lectin affinity was observed for the latter conjugates. The conjugates showed a high affinity for HepG2 cells with ASGPRs and, consequently, a strong in vitro antitumor activity on the cells. It is concluded that the manner of pullulan modification is a key factor contributing to the photodynamic antitumor activity of modified C(60).     

Preparation of Hierarchically Structured Amorphous Carbon Monoliths with Closed Spherical Mesopores via the Lower Critical Solution Temperature Phase Transition

Some polymer mixture systems become immiscible above a specific temperature, the so‐called lower critical solution temperature (LCST). In this work, the LCST behavior of a mixture of poly(ethylene oxide)‐block‐poly(propylene oxide)‐block‐poly(ethylene oxide) triblock copolymers and phenolic resin oligomers is observed, and the corresponding phase transition is exploited to develop a facile route to hierarchically structured carbon monoliths. Whereas evaporation‐induced self‐assembly generates hexagonal channels in the monoliths, an additional phase transition at the LCST leads to an ordered arrangement of isolated pores. The fabrication method involves annealing the gel‐phased mixture with polymeric microbeads in a 3D‐structured mold at the LCST, followed by thermosetting and a carbonization process. The LCST phase transition behavior is observed experimentally by in situ small‐angle X‐ray scattering, optical transparency measurements, differential scanning calorimetry, and infrared spectroscopy. The fundamental mechanism of the LCST phase transition is further investigated by atomistic molecular dynamics simulations.     

DL—聚乳酸微球大鼠体内的降解

采用凝胶渗透色谱，通过观察ＤＬ－聚乳酸分子量的变化，对两种不同分子量的ＤＬ－ＰＬＡ微球在大鼠体内的降解进行了研究，探讨分析了降解机理。结果表明：ＤＬ－ＰＬＡ微球在大鼠体内的降解为简单本体水解；初始ＤＬ－ＰＬＡ分子量的不同对降解速率影响不显著。     

Macroporous poly(N-isopropylacrylamide) hydrogels with fast response rates and improved protein release properties

A series of temperature-sensitive poly(N-isopropylacrylamide) (PNIPA) hydrogels with large pore size and fast response were prepared by carrying out polymerizations in aqueous sodium chloride solutions with different concentrations. In comparison with conventional PNIPA hydrogels, the PNIPA gels thus prepared have remarkably larger swelling ratios below their lower critical solution temperature (LCST), and exhibit much faster response rates as the temperature is raised above their LCST. The improved properties are due to the presence of inorganic salt, NaCl, which leads the phase separation and formation of a heterogeneous porous structure during the polymerizations. The study on the drug release properties shows the macroporous hydrogels exhibit modulated release in response to temperature. The model protein, bovine serum albumin (BSA), can be released completely from the porous hydrogels at the temperature lower than the LCST because the pore size of the hydrogels is larger than the protein molecules. However, the release of BSA from the gels almost stops after a "burst" release in the initial stage at the temperature higher than the LCST because the pores are closed at the high temperature.     

Effect of Modification Manner on the Photodynamic Antitumor Activity of C60 Modified with Pullulan

To design a novel cytospecific photosensitizer for photodynamic antitumor therapy, a fullerene (C₆₀) was chemically modified with pullulan, a water-soluble polysaccharide with a high affinity for asialoglycoprotein receptors (ASGPRs). The effect of the molecular weight of pullulan and the modification manner to C₆₀ on the photodynamic antitumor activity of C₆₀ modified with pullulan was evaluated. In this study, two modification manners were selected. First, ethylene diamine was chemically introduced to the hydroxyl groups of pullulan with different molecular weights. Then, C₆₀ was coupled to pullulan through the amino groups introduced (pendant type). Second, ethylene diamine was introduced to the terminal aldehyde groups of pullulan by a reductive amination reaction, and then the pullulan with the terminal amino groups was coupled to C₆₀ (terminal type). Irrespective of the pullulan molecular and the modification manner, the C₆₀–pullulan conjugates exhibited a similar ability to generate superoxide anions upon light irradiation. Comparing the C₆₀–pullulan conjugates of pendant and terminal types, a high lectin affinity was observed for the latter conjugates. The conjugates showed a high affinity for HepG2 cells with ASGPRs and, consequently, a strong in vitro antitumor activity on the cells. It is concluded that the manner of pullulan modification is a key factor contributing to the photodynamic antitumor activity of modified C₆₀.     

Synthesis and Characterization of Thermosensitive Poly(N‐Vinyl Caprolactam)‐Grafted‐Aminated Alginate Hydrogels

Thermosensitive hydrogels are characterized by the drastic and reversible change of their physical properties with temperature. Herein is presented the development of a thermosensitive poly(N‐vinylcaprolactam)‐grafted‐aminated alginate (PNVCL‐g‐Alg‐NH₂) having a temperature‐dependent phase transition close to physiological temperature. The hybrid copolymer is formed through the combinational use of chemical and physical methods, that is, carbodiimide chemistry, and ionotrophic gelation by calcium cations. PNVCL‐g‐Alg‐NH₂ exhibits a phase transition at ≈35 °C, and temperature‐dependent water uptake. Copolymerization with PNVCL leads to a decrease in the water uptake of aminated alginate, while improving its thermal stability. Model protein (bovine serum albumin) release from PNVCL‐g‐Alg‐NH₂ scaffolds indicates a higher rate of release below the lower critical solution temperature (LCST) than that of the above, owing to the fact that PNVCL chains collapse at above the LCST and forms a more compact network. In vitro cytotoxicity and hemocompatibility analyses confirm that PNVCL‐g‐Alg‐NH₂ scaffolds are basically non‐cytotoxic and non‐hemolytic.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels arc synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTS) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (poly(IPAAm-(-o-DMAAiii)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37°C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31°C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36°C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.     

Factors affecting size and swelling of poly(ethylene glycol) microspheres formed in aqueous sodium sulfate solutions without surfactants

The LCST behavior of poly(ethylene glycol) (PEG) in aqueous sodium sulfate solutions was exploited to fabricate microspheres without the use of other monomers, polymers, surfactants or organic solvents. Reactive PEG derivatives underwent thermally induced phase separation to produce spherical PEG-rich domains that coarsened in size pending gelation, resulting in stable hydrogel microspheres between ≈1 and 100 microns in size. The time required to reach the gel point during the coarsening process and the extent of crosslinking after gelation both affected the final microsphere size and swelling ratio. The gel point could be varied by pre-reaction of the PEG derivatives below the cloud point, or by controlling pH and temperature above the cloud point. Pre-reaction brought the PEG derivatives closer to the gel point prior to phase separation, while the pH and temperature influenced the rate of reaction. Dynamic light scattering indicated a percolation-to-cluster transition about 3–5 min following phase separation. The mean radius of PEG-rich droplets subsequently increased with time to the 1/4th power until gelation. PEG microspheres produced by these methods with controlled sizes and densities may be useful for the production of modular scaffolds for tissue engineering.     

Synthesis and swelling-deswelling kinetics of poly(N-isopropylacrylamide) hydrogels grafted with LCST modulated polymers

Two types of thermo-responsive hydrogels are synthesized to obtain comb-type grafted gels with different lower critical solution temperatures (LCSTs) between graft chains and cross-linked backbone networks: these are poly(N-isopropylacrylamide) (PIPAAm) cross-linked hydrogels grafted with poly(N-isopropylacryl amide-co-N,N-dimethylacrylamide) (poly(IPAAm-co-DMAAm)) maintaining a freely mobile end and poly(IPAAm-co-DMAAm) cross-linked hydrogels grafted with PIPAAm chains. The effect of graft chain hydrophilic/hydrophobic balance as well as its mobility on deswelling kinetics of these grafted gels are investigated through the polymer LCST modulation and external temperature changes. The deswelling rate of poly(IPAAm-co-DMAAm)-grafted PIPAAm gel increases with increasing in temperature. This gel shows a discontinuous increase of the deswelling rate when the temperature is applied from below to above the graft chain LCST (37 degrees C). The deswelling rate of PIPAAm-grafted poly(IPAAm-co-DMAAm) gel increases continuously when the temperature is applied from below to above the graft chain LCST (31 degrees C). Due to the strong hydrophilicity of backbone network, the hydrophobic aggregation force weak. In contrast to the graft-type gels, normal-type poly(IPAAm-co-DMAAm) cross-linked gel without graft chains demonstrates the discontinuous decrease for the deswelling rate when the temperature is applied from below to above the polymer LCST (36 degrees C), entrapping water inside the gel due to the formation of an impermeable dense skin layer at the gel surface. These gel deswelling mechanisms are discussed in terms of gel structures.