Poly(N-isopropylacrylamide)/poly[(N-acetylimino)ethylene] thermosensitive block and graft copolymers

Block and graft copolymers with poly(N-isopropylacrylamide) and poly[(N-acetylimino)ethylene] (PNAI) sequences were synthesized via PNAI derivatives (macroinitiators or macromers). The polymerization yields for block copolymers synthesized in ethanol, using the PNAI macroinitiator, were low (<10%), except where photochemical polymerization was applied. By contrast, for the copolymerizations of N-isopropylacrylamide with the PNAI macromers, performed in alcoholic solution, quite high polymerization yields, around 80-90%, were reached. ¹H-NMR and IR spectral and differential scanning calorimeter thermal data confirmed the copolymer formation. Thermosensitivity of the copolymers was investigated by means of turbidimetric technique as a function of their nature, average molecular weight and composition. It was found that the length of the chain of the PNAI macromer and the content in hydrophilic PNAI units of the resulted copolymer affected this behavior.     

Thermosensitive aggregates self-assembled by an asymmetric block copolymer of dendritic polyether and poly(N-isopropylacrylamide)

An asymmetric linear-dendritic block copolymer of polyether dendrimer and poly(N-isopropylacrylamide) was prepared by an atom transfer radical polymerization method. The self-assembly behavior and thermosensitive property of this copolymer in water were studied by dynamic light scattering (DLS), transmission electron microscopy (TEM) and fluorescence probe spectroscopy. It was found that the thermosensitive phase transition takes place at the temperature of 37.5 °C; simultaneously the spherical aggregates grow into larger entangled nanotubules. The unique temperature-sensitive supramolecular aggregates may make them especially useful as intelligent capsules for drug delivery systems and as chemical sensors.     

Complexation between poly(N,N-diethylacrylamide) and poly(acrylic acid) in aqueous solution

The complexation between poly(N,N-diethylacrylamide) (PDEA) and poly(acrylic acid) (PAA) in aqueous solution was studied by viscometric, potentiometric, and fluorescence techniques. It was found that an interpolymer complex formed between the two polymers through hydrogen bonding interactions with the stoichiometry of r=0.6 (r is unit molar ratio of PAA/PDEA), and the complex formation show the dependence on pH values. The phase behaviour studies showed that the lower critical solution temperature of the PDEA-PAA aqueous solution gradually increased with the increasing of r from 0.01 to 0.15, until a soluble system in the whole temperature region was obtained, which remained in the range of r=0.15-0.3. At higher PAA concentrations, when r is above 0.3, the system appeared phase separation, and almost no temperature dependence was observed. Based on these conclusion and structure characteristics of PDEA and PAA, a model containing only short sequences of monomer residues was proposed for the structure of PDEA-PAA complex.     

Random copolymers of N-isopropylacrylamide and methacrylic acid monomers with hydrophobic spacers: pH-tunable temperature sensitive materials

Two series of random copolymers of N-isopropylacrylamide (NIPAAm) and comonomers derived from methacrylic acid with a different number of methylene units as hydrophobic spacers (n=4, 7 and 10) were synthesized via free radicals. The first series was prepared having the acid groups methoxy-protected while the second series have the acid groups free. The NIPAAm-copolymers of both series were prepared varying the comonomer content from 5 to 20 mol%. All the copolymers were characterized by FTIR, DSC, ¹H NMR and SLS. The aqueous solution behaviour of the copolymers having methoxy-protected acid groups shows that the comonomer increases the hydrophobicity of the copolymer chain and decreases its lower critical solution temperature (LCST). For the copolymers having free acid groups, hydrogen-bonding is responsible for a further decrease in the LCST of these copolymers in pure water. In buffer solutions, every acid comonomer have a critical ionization degree (α_crit) above which the LCST increases with increasing comonomer content while at an ionization degree lower than α_crit the LCST decreases with increasing comonomer content. In dependence of comonomer content, number of methylene units in the spacer and the pH of the buffer solution, the LCST of the copolymers can be varied widely, showing that these random copolymers have pH-tunable temperature sensitivity.     

Synthesis and characterization of novel vinyl copolymers containing N-vinylphthalimide: Comonomers reactivity ratios and thermal stability

N-Vinylphthalimide (NVPh) was copolymerized with p-methylstyrene (PMS), p-methoxystyrene (PMOS) and p-chlorostyrene (PClS) at 60 °C, with 2,2′-azo-bis-isobutyronitrile as an initiator. Copolymer composition was determined by elemental analysis in case of the N-vinylphthalimide and p-methylstyrene comonomer pair, whereas proton nuclear magnetic resonance was used for the analysis of the two other copolymers.The reactivity ratios for each comonomer pair were estimated by the classical Fineman-Ross and Kelen-Tüdõs linear techniques. These data showed that N-vinylphthalimide was less reactive in all the cases and that the comonomer distribution, that was basically random in the poly(N-vinylphthalimide-co-p-methylstyrene) and poly(N-vinylphthalimide-co-p-chlorostyrene) copolymers, was rather alternate in the third poly(N-vinylphthalimide-co-p-methoxystyrene) copolymer. The difference observed in the reactivity ratios was discussed in reference to the structure of the comonomer units and the parent radicals. The thermal properties of the copolymers and model homopolymers were investigated by differential scanning calorimetry and thermogravimetric analysis.     

Dynamic deswelling studies of poly(N-vinyl-2-pyrrolidone/itaconic acid) hydrogels swollen in water and terbinafine hydrochloride solutions

Deswelling kinetics of water and terbinafine hydrochloride adsorbed poly(N-vinyl-2-pyrrolidone/itaconic acid) P(VP/IA) hydrogels were investigated. Hydrogels were prepared by irradiating the ternary mixture of VP/IA and cross-linking agent ethylene glycol dimethacrylate (EGDMA) in water by γ-rays at ambient temperature. Hydrogels swelled in pure water and terbinafine hydrochloride (TER-HCl) solutions at room temperature and deswelling or water loss were investigated between 4 and 45 °C temperature range and on human skin. The influence of IA content, % swelling, temperature and TER-HCl content on the water loss from gel matrix were investigated. Induction time for 80% water loss from hydrogel systems are found to increase from 9.6 to 21.2 h by increasing IA content in the gel system at 25 °C and decreased by 11 h with addition of TER-HCl in the gel system. Kinetic analyses had shown that the basic properties affecting the water loss behavior of these hydrogels are the IA and TER-HCl content and temperature of the medium.     

Synthesis and monomer reactivity ratios of (vinylcyclohexane-co-N-vinyl-2-pyrrolidone) copolymer

A copolymer containing vinylcyclohexane (VCH) and N-vinyl-2-pyrrolidone (VP) at different compositions was synthesized and characterized. The monomer reactivity ratios (MRR) were estimated by using the classical Fineman-Ross and Kelen-Tüdõs linear fitting methods. These parameters were also estimated using a nonlinear computational fitting procedure, known as reactivity ratios error in variable model (RREVM). In this case, the values of MRR are r_VP=2.2 and r_VCH=0.0. Composition shifts and MRR values for (vinylcyclohexane-co-N-vinyl-2-pyrrolidone) copolymer (VCH-co-VP) are interpreted in terms of the relative comonomeric structures. A copolymer with zones containing VP blocks with isolated units of VCH between them is obtained. The presence or absence of the resonance stabilization effect is taken into account. The results are compared with those of similar related copolymeric systems.     

ATRP synthesis and association properties of temperature responsive dextran copolymers grafted with poly(N-isopropylacrylamide)

Temperature responsive copolymers of dextran grafted with poly(N-isopropylacrylamide) (Dex-g-PNIPAAM) were prepared by atom transfer radical polymerization (ATRP) in homogeneous mild conditions without using protecting group chemistry. Dextran macroinitiator was synthesized by reaction of dextran with 2-chloropropionyl chloride at room temperature in DMF containing 2% LiCl. ATRP was carried out in DMF:water 50:50 (v/v) mixtures at room temperature with CuBr/Tris(2-dimethylaminoethyl)amine (Me₆TREN) as catalyst. Several grafted copolymers with well defined number and length of low polydispersity grafted chains were prepared. Temperature induced association properties in aqueous solution were studied as a function of temperature and polymer concentration by dynamic light scattering, fluorescence spectroscopy and atomic force microscopy (AFM). LCST, ranging from 35 to 41 °C, was significantly affected by number and length of grafted chains. The fine tuning of LCST around body temperature is an important characteristic not obtainable by conventional radical grafting of PNIPAAM. Well defined spherical nanoparticles were formed above the LCST of PNIPAAM. Hydrodynamic diameter was in the range 73-98 nm.     

Preparation and characterization of sodium carboxymethylcellulose/poly(N-isopropylacrylamide)/clay semi-IPN nanocomposite hydrogels

A new kind of pH-/temperature-responsive semi-interpenetrating polymer network hydrogels based on linear sodium carboxymethylcellulose (CMC) and poly(N-isopropylacrylamide) (PNIPA) cross-linked by inorganic clay (CMC/PNIPA/Clay hydrogel) was prepared. The temperature- and pH-responsive behaviors, the mechanical properties of these hydrogels were investigated. The CMC/PNIPA/Clay hydrogels exhibited a volume phase transition temperature around 32 °C with no significant deviation from the conventional PNIPA hydrogels. The swelling ratio of the CMC/PNIPA/Clay hydrogels gradually decreased with increasing the contents of clay. The influence of pH value on swelling behaviors showed that there is a maximum swelling ratio at pH 5.9. Moreover, the CMC/PNIPA/Clay hydrogels exhibited excellent mechanical properties with high tensile stress and elongation at break in excess of 1200%.     

H NMR study of temperature-induced phase separation in solutions of poly(N-isopropylmethacrylamide-co-acrylamide) copolymers

¹H NMR spectroscopy was applied to investigate temperature-induced phase separation in solutions of poly(N-isopropylmethacrylamide-co-acrylamide) [P(IPMAm/AAm)] random copolymers in D₂O, D₂O/ethanol and D₂O/acetone. The NMR relaxation behaviour of water (HDO) was also examined. The effects of P(IPMAm/AAm) composition and the ethanol or acetone content in the mixed solvents on the temperature, width and extent of the phase transition as well as on the mobility of polymer segments and water molecules were characterized. For D₂O solutions of the copolymers prepared with the AAm fraction in the polymerization mixture not exceeding 25 mol% ¹H NMR spectra show dynamic heterogeneity of copolymer chains in mesoglobules where AAm sequences and surrounding short IPMAm sequences are hydrated and mobile, while sufficiently long IPMAm sequences are dehydrated and their mobility is strongly reduced. The obtained results are consistent with the idea that P(IPMAm/AAm) copolymer mesoglobules are rather porous and disordered.     

Effects of synthesis-solvent on swelling and elastic properties of poly(N-isopropylacrylamide) hydrogels

Thermosensitive N-isopropylacrylamide (NIPA) hydrogels were synthesized by a free radical copolymerization with N,N′-methylenebisacrylamide (MBAA) in four solvents: water, ethanol, acetone and N,N-dimethylformamide. The swelling and elastic properties of the hydrogels were affected by the synthesis-solvents; the hydrogels (e.g. NIPA/MBAA = 1000/50 mol/m³-pre-gel solution) synthesized in water have smaller swelling volume and larger shear modulus at 10 °C than those synthesized in amphiphilic solvents. The network structure of hydrogels was estimated in terms of the conversion and two sorts of effective crosslinking density based on the Flory theory and the concentration of crosslinker. The hydrogels synthesized in water can have the microscopic inhomogeneous network arising from the entanglement of polymer chains, while the hydrogels synthesized in amphiphilic solvents can have the homogeneous network arising from the polymer concentration lower than the pre-gel solution and can be similar in network structure to the lightly crosslinked hydrogel synthesized in water.     

Synthesis and phase separation of amine-functional temperature responsive copolymers based on poly(N-isopropylacrylamide)

Free radical copolymerizations of N-isopropyl acrylamide (NIPAM) and cationic N-(3-aminopropyl) methacrylamide hydrochloride (APMH) were investigated to prepare amine-functional temperature responsive copolymers. The reactivity ratios for NIPAM and APMH were evaluated in media of different ionic strength (r_NIPAM = 0.7 and r_APMH = 0.7-1.2). Phase separation behavior of the random copolymers with only 5 mol% of the APMH was found to be suppressed in pure water at temperatures up to 45 °C due to electrostatic repulsion among the cationic amine groups randomly distributed along the copolymer chain. Alternate sequential addition of PNIPAM/APMH mixtures and pure NIPAM was used to provide increased control of the location of APMH units along the chain. Consequently (close to) homo-PNIPAM block(s) were formed as evidenced by its characteristic phase transition at 33 °C. The influences of the monomer feeding time and feeding interval time to the APMH distribution were investigated to prepare copolymers with thermo-induced phase separation under physiologically relevant temperature and to determine the extent of conjugation to poly(ethylene oxide).     

Ascorbate amperometric determination using conducting copolymers from aniline and N-(3-propane sulfonic acid)aniline

The sequential electrochemical polymerization of aniline and N-(3-propane sulfonic acid)aniline (PSA) is proposed to construct a sensor able to detect ascorbate at physiological conditions. Compared to poly(aniline) modified electrode, a device with improved conducting and electrochemical properties at neutral pH is obtained. The electrochemical copolymerization of the same starting materials is also carried out. For a PSA:aniline ratio of 10:90, a polymer with a similar electrochemical behavior to the one grown in the sequential mode is observed.The detection of ascorbate was tested for both configurations at pH 7.2, the modified electrode is able to determine ascorbate at 0 mV versus Ag/AgCl; an optimized sensor constructed by sequential polymerization can easily detect ascorbate concentrations with a detection limit of 2.2 μM. Uric acid and dopamine does not interfere in the ascorbate determination.     

Study on interaction between Tb(III) and poly(N-isopropylacrylamide)-g-poly(N-isopropylacrylamide-co-styrene) core-shell nanoparticles

Based on the synthesis of poly(N-isopropylacrylamide-co-styrene) P(NIPAM-co-St) and poly(N-isopropylacrylamide) (PNIPAM) grafted P(NIPAM-co-St) core-shell nanoparticle, a new kind of thermoresponsive and fluorescent complex of Tb(III) and PNIPAM-g-P(NIPAM-co-St) (PNNS) was successfully prepared. The PNNS-Tb(III) complex was characterized with the different techniques. It was found that when PNNS with the core-shell structure interact with Tb(III), Tb(III) mainly bonded to O of the carbonyl groups of PNNS, forming the novel PNNS-Tb(III) complex. After forming the complex, the emission fluorescence intensity of Tb(III) in the complex is significantly enhanced. Especially, the maximum emission intensity of the PNNS-Tb(III) complex at 545 nm is enhanced about 223 times comparing to that of the pure Tb(III) because the effective intramolecular energy transfer from PNNS to Tb(III). The intramolecular energy transfer efficiency from PNNS to Tb(III) reaches 50%. The fluorescence intensity is related the weight ratio of Tb(III) and PNNS in the PNNS-Tb(III) complex. When the weight ratio of Tb(III) and the PNNS is 12 wt%, the enhancement of the emission fluorescence intensity at 545 nm is highest. This novel fluorescence characterization of the PNNS-Tb(III) complex may be useful in the fluorescence systems and the biomedical field.     

Lower critical solution temperature control and swelling behaviour of physically crosslinked thermosensitive copolymers based on N-isopropylacrylamide

In this contribution we have developed thermosensitive polymer matrices based on N-isopropylacrylamide (NIPAAm). Preparation of the hydrogels involved photopolymerisation of a combination of NIPAAm, 1-vinyl-2-pyrrolidinone (NVP) and distilled water, in appropriate amounts and contained a UV-light sensitive initiator called 1-hydroxycyclohexylphenylketone. As NIPAAm monomer could be readily dissolved in mixtures of liquid NVP and distilled water, the use of organic solvents was not required in the polymerisation process. Furthermore, chemical crosslinking agents are not needed in the synthesis. By alternating the feed ratio, hydrogels were synthesised to have lower critical solution temperatures (LCST) in the vicinity of 37 °C. This ability to shift the phase transition temperature of the gels provides excellent flexibility in tailoring transitions for specific uses. The transition temperature of the pseudo gels was established using cloud point measurement and modulated differential scanning calorimetry (MDSC). The chemical structure of the xerogels was characterised by means of Fourier transform infrared spectroscopy (Ftir), while swelling experiments in distilled water indicate that the swelling and dissolution behaviour of the gels is strongly temperature dependent.     

Study on interaction between Tb(III) and poly(N-isopropylacrylamide)

A new kind of the thermo-sensitive and fluorescent complex of poly(N-isopropylacrylamide) (PNIPAM) and Tb(III) was synthesized by free radical polymerization, in which PNIPAM was used as a polymer ligand. The complex was characterized by using X-ray photoelectron spectroscopy (XPS), ultraviolet-visual (UV), Fourier transform infrared (FT-IR) and fluorescence spectroscopy. The results from the experiments indicated that there is a strong interaction between PNIPAM and Tb(III), leading to a decrease in the electron density of nitrogen and oxygen atoms and an increase in the electron density of Tb(III) in the PNIPAM containing Tb(III) by contrast with PNIPAM and Tb(III), respectively, meanwhile, exhibiting that the Tb(III) is mainly bonded to oxygen atoms in the polymer chain of PNIPAM and formed the complex of PNIPAM-Tb(III). After forming the PNIPAM-Tb(III) complex, the emission fluorescence intensity of Tb(III) in the PNIPAM-Tb(III) complex is significantly enhanced because the effective intramolecular energy transfer from PNIPAM to Tb(III). Especially, the emission intensity of the fluorescence peak at 547 nm can be increased as high as 145 times comparing with that of the pure Tb(III). The intramolecular energy transfer efficiency for fluorescence peak at 547 nm can reach as high as 68%. The fluorescence intensity is related the weight ratio of Tb(III) and PNIPAM in the PNIPAM-Tb(III) complex. When the weight ratio is 1.4%, the maximum fluorescence enhancement can be obtained. Nevertheless, the lower critical solution temperature of PNIPAM containing a low content of Tb(III) has not obviously changed after the formation of the complex of PNIPAM-Tb(III) by the interaction between PNIPAM and Tb(III). This novel thermosensitive and fluorescence characterization of the PNIPAM-Tb(III) complex may be useful in the fluorescence systems and the biomedical field.     

Rapid swelling and deswelling in cryogels of crosslinked poly(N-isopropylacrylamide-co-acrylic acid)

Thermally sensitive hydrogels of poly[N-isopropylacrylamide (NIPA)-co-acrylic acid (AA)] hydrogels with N,N-methylene bisacrylamide (BIS) as crosslinker have been synthesized via a two-step procedure in which, the initial polymerisation is conducted for various times at 18 °C, this step being followed by polymerisation for one fixed time at −22 °C. The gravimetrically determined rates of swelling/deswelling for these materials termed “cryogels” prepared by this two-step polymerisation are much higher than those for the same type of hydrogel prepared via conventional methods (30 °C for 24 h). For example the time for the former xerogel to take up 70% of its final water content at 25 °C is just 18 min, compared with a time 300 min for the latter to attain the same uptake of water. During deswelling (shrinking) at 50 °C, which is above the lower critical temperature, the hydrogel loses 60 and 90 wt% water in 1 and 10 min respectively, compared to a timescale for the corresponding crosslinked copolymers prepared by conventional methods of about 100 min for 50 wt% water loss. A third type of hydrogel was made by a cold treatment (CT), for which the hydrogel prepared by conventional polymerization was stored in the frozen state. The swelling rate of these CT xerogels was the same as that for xerogels prepared by conventional polymerization, but the deswelling rate of the former was higher than that of the latter; for example, during deswelling, a loss of 90% water is attained within a few minutes.Scanning electron microscopy, digital photographs and flotation experiments together with swelling ratio studies reveal that the polymeric network of cryogel produced by the two-step polymerization method is characterized by an open structure with more pores and higher swelling ratio but lower mechanical strength compared to the conventional hydrogels. Such rapid response hydrogels have potential applications in separation and drug release technologies for example.     

Thermo- and pH-sensitive comb-type grafted poly(N,N-diethylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors

Poly(N,N-diethylacrylamide) with a terminal hydroxyl end group (PDEA-OH) was synthesized by radical telomerization of N,N-diethylacrylamide (DEA) monomer using 2-hydroxyethanethiol as a chain transfer agent. Macromonomer of thermo-sensitive PDEA was synthesized by condensation reaction of PDEA-OH with acryloyl chloride. The macromonomer was characterized by FTIR and ¹H NMR, and the molecular weight was determined by GPC. Thermo- and pH-sensitive comb-type grafted poly(N,N-diethylacrylamide-co-acrylic acid) (PDEA-co-AA) hydrogels (GHs) were successfully prepared by grafting PDEA chains with freely mobile ends onto the backbone of a cross-linked (PDEA-co-AA) network. The results showed that the deswelling behavior of the hydrogels was dependent on the test temperature. At 45 °C (beneath the VPTT of the hydrogels), both the normal-type hydrogels (NHs) and comb-type grafted P(DEA-co-AA) hydrogels had lower deswelling rates. While at 60 °C (far beyond the VPTT of the hydrogels), the deswelling rates of the GHs were faster than that of the NHs. Furthermore, pulsatile stimuli-responsive studies indicated that the GHs had excellent thermo-reversibility and were superior to the NHs in the magnitude of their swelling ratios to temperature changes. However, the reversibility to pH changes was poor for both the NHs and the GHs.     

Study of free-radical copolymerization of itaconic acid/2-acrylamido-2-methyl-1-propanesulfonic acid and their metal chelates

The monomer reactivity ratios for itaconic acid (IA)/2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) in N,N-dimethylformamide solution using the benzoyl peroxide (Bz₂O₂) as an initiator with different monomer-to-monomer ratios in the feed were investigated by studying the resulting copolymer composition via elemental analysis. Composition results were summarized and various methods were employed to estimate the monomer reactivity ratios including the use of the Error-in Variables-Model method using a computer program, RREVM. The estimates of the reactivity ratios from the EVM method are found to be r_IA = 0.4636 and r_AMPS = 0.0357. These values suggest that IA is more reactive than AMPS and the copolymer will be richer in IA units. Cu(II) and Ni(II) chelates of the copolymers were prepared and the formation constants of each complex were determined by the mole-ratio method using the UV-vis spectroscopy. UV-vis studies showed that the complex formation tendency increased in the followed order: Cu(II) > Ni(II). The copolymers and their metal chelates were characterized by FT-IR spectra and SEM analysis. Also, thermal stabilities of the copolymers and their metal chelates were investigated using TGA and DSC analysis.     

Poly(N-isopropylacrylamide) thermoresponsive cross-linked conjugates containing polymeric soybean oil and/or polypropylene glycol

Synthesis, characterization and solution properties of a new series of the PNIPAM-soybean oil and/or polypropylene glycol, PPG, conjugates (conjugates also referred to as co-networks) have been described. For this purpose free radical polymerization of NIPAM monomer was initiated by macroinitiators based on PSB and/or PPG in order to obtain PSB-g-PNIPAM, PPG-g-PNIPAM and PSB-g-PPG-g-PNIPAM cross-linked graft copolymers. The autooxidation of soybean oil under air at room temperature rendered waxy soluble polymeric soybean oil peroxide associated with cross-linked parts. The soluble polymeric oil macro-peroxide isolated from the cross-linked part was used to initiate the free radical polymerization of NIPAM to give PSB-g-PNIPAM cross-linked copolymer. To obtain PPG-macromonomeric initiator, PPG-MIM, PPG-bis amino propyl ether with Mn 400 (or 2000) Dalton was reacted with 4,4′-azo bis cyanopentanoyl chloride and methacryloyl chloride, respectively. PPG-MIM also initiated the free radical polymerization of NIPAM at 80 °C to yield PPG-g-PNIPAM cross-linked thermoresponsive product. In order to obtain PSB-g-PPG-g-PNIPAM cross-linked triblock copolymer, NIPAM was polymerized by using the mixture of two macroinitiators, PSB and PPG-MIM. PSB contents in the graft copolymers were calculated via elemental analysis of nitrogen in graft copolymers. Thermal analysis, SEM, FTIR and ¹H NMR techniques were used in the characterization of the products. The effect of polymeric soybean oil, PSB, and/or PPG on the thermal response rate of poly(N-isopropylacrylamide, PNIPAM, cross-linked-graft copolymers swollen in water has been investigated by means of swelling-deswelling and drug release behaviors against to temperature change. Lower critical solution temperatures (LCST) of the cross-linked PNIPAM conjugates (conjugates also referred to as co-networks) were determined from the curves of swelling degrees versus solution temperatures. The response temperature of the hydrophobically modified PNIPAM conjugates was reduced to 27 °C, 23 °C and 27 °C for PSB-g-PNIPAM, PPG-g-PNIPAM and PSB-g-PPG-g-PNIPAM, respectively. We have found that the graft copolymers were not pH-responsive. In addition, higher pH ranges cause the hydrolysis of the PSB ester linkages, quickly and makes the cross-linked graft copolymers soluble.The fastest shrinking of the gels was observed by loosing water between 65% and 98% at 50 °C.Methyl orange (MO), was used as a model drug, loaded into cross-linked graft copolymers to examine and compare the effects of controlled release at lower and higher temperatures of lower critical solution temperature (LCST).