Article pubs.acs.org/IECR
Thermoreversible Poly(isopropyl lactate diol)-Based Polyurethane Hydrogels: Effect of Isocyanate on Some Physical Properties Luiza M. Gradinaru,*,†,‡ Constantin Ciobanu,† Stelian Vlad,† Maria Bercea,† and Marcel Popa‡ †
“Petru Poni” Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487, Iasi, Romania Faculty of Chemical Engineering and Environmental Protection, “Gh. Asachi” Technical University, 73 Dimitrie Mangeron Street, 700050, Iaşi, Romania
‡
ABSTRACT: A series of polyurethanes were synthesized from poly(isopropyl lactate)diol, poly(ethylene oxide)− poly(propylene oxide)−poly(ethylene oxide) triblock copolymer, and different aliphatic diisocyanates. The chemical structure and molecular characteristics were investigated by 1H NMR, FT-IR, and GPC analysis. The effect of the isocyanate moiety on the polymer properties was studied. The wetting properties were evaluated from the contact angle determination. The obtained water-soluble polyurethanes present very low critical micelle concentration as determined by surface tension measurements. Aqueous solutions of these polyurethanes underwent a sol−gel−sol transition in a certain range of temperature, as a function of their chemical composition. The gelation for aqueous polyurethane solutions has been also realized under isothermal condition, and the viscoelastic properties of the hydrogels at 37 °C were investigated. The chemical structure of the diisocyanates influences the gelation process as well as the properties of the polyurethane hydrogels. These polyurethane properties might aid in devising new theoretical and practical approaches in many areas, such as pharmacology and materials fabrication.
1. INTRODUCTION The development of many thermoreversible polymers has been progressing rapidly over the past decade.1−3 The characteristic property of these polymers is their ability to form low viscosity aqueous solutions at ambient temperature and creating a gel at a temperature close to that of the human body. These in situ gelling systems show several advantages such as convenience for application because no surgical procedure is required; the risk of infection is low, the hospitalization time is short, and they are less painful; they are water-based and show no problems of solvent toxicity; and they can easily fill the complex shapes. Also, they have been widely studied in many pharmaceutical and biomedical applications as delivery systems of drugs, cells, proteins, and genes,4,5 scaffolds for tissue engineering,6 etc. Because of their biocompatibility,7−10 chemical versatility,11,12 and superior mechanical properties,13 polyurethanes have been extensively investigated for biomedical applications, including cardiovascular devices,14,15 wound dressings,16 and medical supplies.17 Besides their traditional applications, the development of polyurethane hydrogels for novel biomedical applications, including controlled release of drugs18,19 and proteins,20 matrixes in tissue engineering,21,22 etc., has been investigated. The properties of the polyurethane are directly related to their two-phase microstructure, with a hard domain including the diisocyanates and/or a chain extender, and a soft domain constituting the flexible segments. The aromatic diisocyanates were replaced by more biologically friendly compounds such as aliphatic diisocyanates: lysine diisocyanate, hexamethylene diisocyanate, etc. The release of degradation products from the urethane segments of this polyurethane is theoretically harmless. For example, upon degradation of the polyurethanebased L-lysine-ethyl ester diisocyanate is released L-lysine, an © 2012 American Chemical Society
essential amino acid, which will not produce side effects into the body.23 Poly(isopropyl lactate) diol, obtained from polycondensation of D,L-lactic acid with 1,2-propane diol, is a nontoxic, biodegradable, and biocompatible polymer belonging to the class of poly(lactic acid) polymers.24 Because of their good bioresorbability, which leads to the formation of inactive substances for organism, they are suitable for applications in drug delivery.25,26 Another candidate for obtaining the polyurethane soft segments could be the poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) triblock copolymer, commercially known as Pluronic or Poloxamer. This copolymer has thermoreversible properties and undergoes self-assembly into micelles at a low critical micelle concentration due to the hydrophilic/hydrophobic balance. This balance can be adjusted by introducing some chains with hydrophobic or hydrophilic segments. Thus, this copolymer is used extensively in the pharmaceutical application as a vehicle for the controlled release of drugs27 or as a coating for wounds.28 The aim of this work was to synthesize thermoreversible polyurethane hydrogels based on biocompatible and biodegradable compounds and to study the effect of the isocyanate moiety on the polyurethane properties. Thus, we synthesized some polyurethane hydrogels starting from poly(isopropyl lactate)diol, poly(ethylene oxide)−poly(propylene oxide)− poly(ethylene oxide) triblock copolymer, and different aliphatic diisocyanates. The thermal-induced gelation (which can be easily controlled from the chemical structure) and the excellent Received: Revised: Accepted: Published: 12344
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mechanical properties of the hydrogels at 37 °C lead us to recommend these polyurethane hydrogels to be used for drug or enzyme delivery.
determined by GPC. The structure of the resulting polyol was confirmed by FT-IR and 1H NMR. FT-IR (cm−1): 3517 (w, ν, O−H), 2996, 2946 (w, νasym, −CH2 and −CH3), 2882 (vw, νsym, −CH2 and −CH3), 1753 (vs, ν, CO), 1192 (s, ν, C−CO−O), 1093 (s, ν, O−C−C). 1 H NMR (400 MHz,CDCl3, δ in ppm): 5.17 (−OCO−CH(CH3)−OCO−), 4.37 (−OCO−CH(CH3)−OH), 4.19 (−OCO−CH2−CH−), 3.82 (−OH), 1.57−1.27 (−CH3). 2.3. Synthesis of Polyurethanes. The polyurethanes were synthesized by bulk polymerization method using poly(isopropyl lactate) diol (PILD) and poly(ethylene oxide)− poly(propylene oxide)−poly(ethylene oxide) triblock copolymer (PEO−PPO−PEO) as soft segments and different aliphatic diisocyanates, ethyl ester L-lysine diisocyanate (LDI), 1,6-hexamethylene diisocyanate (HDI), and isophorone diisocyanate (IPDI) as the hard segment. In Scheme 2 is shown the structure of these polyurethanes. Typically, 0.01 mol of PILD and 0.01 mol of PEO−PPO−PEO were dehydrated 4 h in a three-neck glass reactor equipped with a mechanical stirrer at 80 °C, under vacuum (0.2 mmHg). Next, the required amount of diisocyanate was added dropwise to the mixture so that the molar ratio NCO:OH was 1:0.8. To the reaction mixture was also added 3 drops of catalyst (dibutyltin dilaurate). The reaction between diisocyanate and macrodiol took place for 8 h under stirring and dry nitrogen atmosphere at 70 °C. The resulting polymers were denominated PU-HDI, PULDI, and PU-IPDI, respectively. 2.4. Characterization of the Polyurethanes. 1H NMR spectra were recorded at room temperature on a Bruker Avance DRX-400 spectrometer (400 MHz). All of the samples were dissolved in deuterated dimethyl sulfoxide (DMSO-d6). The characterization of the functional groups was carried out by FTIR analysis using a Bruker Vertex 70 type spectrometer (U.S.), with a diamond crystal, provided with software for spectral processing. The sample surface was scanned in the range 400−4000 cm−1, at a 45° angle. The FTIR spectra were recorded at a constant temperature of 25 °C. The average molecular weight and the polydispersity of the samples were determined by gel permeation chromatography (GPC), with a GPC PL-EMD 950 evaporative mass detector instrument. The system columns were thermostatted at 25 °C. Calibration was performed with narrow polydispersity polystyrene standards (Polymers Laboratories Ltd.). The samples were eluted with DMF, and the flow rate was 0.7 mL min−1. Analysis of the elution data was performed using a computer program based on normalization of the chromatograms. 2.5. Contact Angle Measurements. Static contact angles were measured by the sessile-drop method, with a CAM-101 (KSV Instruments, Helsinki, Finland) contact angle measure-
2. EXPERIMENTAL SECTION 2.1. Materials. D,L-Lactic acid (90%) and propilenglicol (>98%) were purchased from Fluka AG. All of the reagents were of analytical grade and used without further purification. Poly(ethyleneglycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO−PPO−PEO) with Mn of ca. 5800 Da was purchased from Sigma-Aldrich and used as received. Ethyl ester L-lysine diisocyanate (LDI) was supplied by Infine Chemicals, China. 1,6-Hexamethylene diisocyanate (HDI) and isophorone diisocyanate (IPDI) were purchased from Aldrich. All diisocyanates were used as received, without further purification. 2.2. Synthesis of Poly(isopropyl lactate) Diol. Poly(isopropyl lactate) diol was prepared by direct polycondensation of a racemic mixture of D- and L-lactic acid and 1,2-propane diol as shown in Scheme 1. Briefly, in a three-neck roundScheme 1. Synthesis Route of Poly(isopropyl lactate) Diol
bottom flask equipped with a mechanical stirrer, a predetermined amount of D,L-lactic acid was charged and placed in an oil bath at 100 −150 °C under vacuum (0.2 mmHg) for 12 h. The compound was maintained at this temperature until a desired molecular weight was attained. Next, the product was washed with anhydrous methanol and dried under vacuum to remove the cyclic compound. The final product was reacted with a calculated amount of 1,2-propane diol at 150−170 °C for 4 h, under stirring and progressive vacuum. pToluenesulfonic acid was used as catalyst for this synthesis. The traces of catalyst and oligomers were removed by washing with chloroform and water, and then the product was dried under vacuum (1.2 mmHg) for 8 h. The number average molecular weight of the final product was 2000 Da as Scheme 2. Structure of Polyurethanes
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Figure 1. 1H NMR spectra of the polyurethanes: (a) PU-HDI, (b) PU-LDI, and (c) PU-IPDI.
behavior of the polymer samples in conditions close to that of the human body, the evolution of the viscoelastic parameters in time was followed at 37 °C and at constant frequency of oscillation (ω = 1 rad s−1) and shear stress (1 Pa). The samples kept at 4 °C were put into the geometry of the rheometer for which the temperature was also fixed at 4 °C, and the gap of 500 μm was reached. Next, the geometry with the sample was heated at 37 °C, and as soon as the thermal equilibrium was established, the viscoelastic parameters were monitored.
ment system equipped with a liquid dispenser, video camera, and drop-shape analysis software, at room temperature. Double distilled water, ethylene glycol, diiodomethane, and 1-octanol were used as solvents for these studies. For each kind of liquid, three different regions of the surface were selected to obtain a statistical result. 2.6. Determination of Critical Micelle Concentration. The critical micelle concentration (CMC) was determined from surface tension measurements of initial 0.1% aqueous solutions of polymers at room temperature, using Wilhelmy method and a Sigma 700 tensiometer (KSV Instruments, Finland). 2.7. Rheological Measurements. Steady shear and dynamic oscillatory investigations were carried out at 37 °C with a Bohlin CVO rheometer equipped with a Peltier device for the temperature control. The measurements were performed by using parallel plate geometry, the upper plate having a radius of 30 mm (gap of 500 μm). Also, the behavior of the sample in temperature sweep tests was followed from 0 to 80 °C. To prevent the water evaporation, an antievaporation device was used. Prior to oscillatory measurements, the amplitude sweep tests were made at a constant frequency (ω) of 1 rad s−1 to establish the linear viscoelastic range when the storage (G′) and loss (G″) moduli as well as the loss tangent (tan δ) are independent of the strain amplitude. The linear viscoelastic regime is reached for shear stress lower than 1 Pa. Hydrogels aqueous solutions of 15% concentration were prepared and were then stored at 4 °C overnight before rheological measurements were performed. To determine the
3. RESULTS AND DISCUSSION 3.1. Synthesis and Characterization of Polyurethanes. The polyurethanes were synthesized by polyaddition of the isocyanate groups and the hydroxyl groups of the PILD and PEO−PPO−PEO. The chemical structures of polyurethane (Scheme 2) were verified by 1H NMR and FT-IR spectroscopy. Figure 1 shows the 1H NMR spectrum of PU-HDI, PU-LDI, and PU-IPDI in DMSO-d6, in which all proton signals belonging to the row material segments are confirmed. The peaks belonging to the poly(isopropyl lactate)diol segments were found at 1.46 (−CH3, b), 3.44−3.52 (−CH2−, h), and ∼5.15 (−CH−, j) ppm, respectively.29 The signals corresponding to methyl protons (−CH3, a), methylene (−CH2−, g), and methine (−CH−, i) groups in the PEO−PPO−PEO segments are observed at 1.03, 3.30−3.35, and 3.44−3.52 ppm, respectively.30 Thus, the 1H NMR results clearly indicate the coexistence of the PILD and PEO−PPO−PEO segments. The protons from the urethane moiety (−NH, k) were found at ∼7.16 ppm. 12346
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The regions of carbonyl stretching vibration are important because these regions provide information on the mode of hydrogen bonding. Thus, the ratio of the hydrogen-bonded carbonyl groups to the free counterparts was calculated by the ratio of the area of hydrogen-bonded to free carbonyl groups. Table 1 shows that the ratio of the area of hydrogen-bonded to
The FT-IR absorption spectra of the polyurethanes are shown in Figure 2.
Table 1. Ratio Area for the Carbonyl and −NH Groups sample
H-bonded/free COa
H-bonded/free N−Hb
PU-HDI PU-LDI PU-IPDI
1.97 1.40 1.58
1.66 0.51 0.60
Area (1740−1680 cm−1)/area (1787−1740 cm−1). bArea (3444− 3243 cm−1)/area (3660−3444 cm−1). a
free carbonyl groups is in the following order: PU-HDI > PUIPDI > PU-LDI. Similar results were also obtained from the N−H stretching vibration analysis. This indicates that PU-HDI consists of more orderly packed urethane hard segment domains than two other polyurethanes. The steric nonregularity of the LDI urethane moiety does not form a strong hydrogen bond, resulting in disorder in urethane hard segment domains. Thus, from this table and further from the deconvolution of the carbonyl bands, it can be observed that the PU-HDI has the most crystalline structure. The morphological changes of these polyurethane structures can be better highlighted by deconvolution of the carbonyl band using Gaussian function. These deconvolutions were performed in 1787−1680 cm−1 region and are illustrated in Figure 3. In this figure, three different samples are distinguished, because the deconvolution peaks varies in height, width, and wavenumbers. Thus, the deconvolution peaks from the higher frequency are assigned to the free CO stretching vibration, and those from lower frequency are attributed to the H-bonded CO stretching vibration.31,32 The deconvolution peaks at higher frequencies correspond to the free carbonyl groups, without any hydrogen bonds from the urethane or ester structure (Figure 4). The absorption bands around 1720 cm−1 are attributed to the urethane end group associated with an ester group. The hydrogen bond between the urethane CO group of one unit and the urethane N−H group of another appears around 1700 cm −1 (urethane−urethane structures).33−35 The average molecular weight (Mw), the number average molecular weight (Mn), and the molecular weight distribution (Mw/Mn) were determined using gel permeation chromatography (GPC). Table 2 shows the molecular weights and polydispersity of these three synthesized polyurethanes. From this table, we notice that the number average molecular weight (Mn) of these polyurethane ranges from 39 000 to 45 700 Da. PU-HDI has the highest number average molecular weight, and, in contrast, PU-LDI has the lowest Mn. Polydispersity (Mw/Mn) was in the range 1.26−1.3. 3.2. Contact Angle and Surface Free Energy. Because the interaction between biomaterials and blood occurs at their interface, the blood compatibility of biomaterials depends strongly on their surface characteristics. Solid surface dynamics can be described by contact angle measurements. The contact angle is the angle that is formed by the baseline and the tangent to the drop contour at the three-phase point.36 This value is specific for any given system being determined by the
Figure 2. FTIR spectra of the polyurethanes.
All of the polyurethane spectra are substantially similar to each other and demonstrate the presence of the expected functional groups. Thus, the presence of the absorption bands in the 3700−3200 cm−1 region has been assigned to the O−H and N−H stretching vibration. The peaks at 3580 and 3520 cm−1 correspond to the O−H stretching vibration from the PEO−PPO−PEO and PILD, respectively. The peaks at lower frequency (3343 cm−1) are characteristic of the H-bonded N− H stretching vibration with urethane carbonyl. Between 3000 and 2700 cm−1 are four characteristic bands due to the asymmetric and symmetric stretching vibration of −CH2 and −CH3 groups. Thus, the peaks at 2970 and 2931 cm−1 correspond to the asymmetric and symmetric stretching vibrations of −CH2 groups from PILD and PEO−PPO−PEO segments. The peaks at 2896 and 2870 cm−1, respectively, are due to the asymmetric and symmetric stretching vibration of −CH3 groups. The peak at 1750 cm−1 corresponds to the stretching vibration of free carbonyl υ(CO), and at 1720 cm−1 is the peak attributed to H-bonded carbonyl from the ester and urethane structures. At 1533 cm−1 is the characteristic peaks of deformation vibration δ(N−H), which overlaps with the stretching vibration ν(C−N) (amide II). The absorption bands in the 1400−1300 cm−1 region are attributed to the vibration deformation of δ(CH2) and δ(CH3) groups. The peak at 1296 cm−1 corresponds to deformation vibration δ(N−H), which overlaps with the stretching vibration ν(C−N) (amide III) and at 1250 cm−1 is the deformation vibration of δ(OH) groups. The 1100−900 cm−1 region is attributed in special to the stretching vibration of ν(C−O−C) from esteric and etheric functional groups. Thus, the shoulder at 1153 cm−1 can be attributed to the stretching vibration of ν(−C(O)−O−C−) from the urethane and ester groups. The intensive peak observed at 1107 cm−1 can be assigned to the stretching vibration of ν(−C(O)−O−C−) from esteric groups that overlaps with the stretching vibration ν(C−O−C) from aliphatic ether. At 933 cm−1 is the peak characteristic of the stretching vibration ν(C−O−C). The peaks at 865 and 842 cm−1 correspond to the deformation vibration δ(N−H), which overlaps with the stretching vibration ν(C−N) (amide IV). 12347
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Figure 3. Deconvolution of the carbonyl bands of the polyurethanes using the Gauss method.
which quantify the characteristic of the solid surface and its wettability. The surface energy of the films was calculated using the Young equation: γLV cos θ = γSV − γSL
where γSV is the energy of the surface, γSL is the interfacial tension between the solid and the drop, γLV is the liquid−vapor surface tension, and cos θ is the contact angle of the drop with the surface.36 The surface tensions (γSV, γSL) can be divided into two components: polar component (γpSV, γpSL) including two types of coulomb interactions dipole−dipole and dipole− induced dipole, and dispersive components (γdSV, γdSL) represent the van der Waals interactions. The interfacial solid−liquid tension is represented by the equations:
Figure 4. Some possible intramolecular hydrogen bonds formed in the polyurethane systems.
Table 2. Molecular Characteristics of the Polyurethanes sample
Mn (Da)
Mp (Da)
Mz (Da)
Mw/Mn
CMC (mol L−1)
PU-HDI PU-LDI PU-IPDI
45 699 39 108 41 273
55 512 49 150 50 242
74 541 61 529 71 146
1.29 1.26 1.30
3.16 × 10−7 3.95 × 10−7 5.09 × 10−7
(1)
(
γSL = γSV + γLV − 2
p p γSV γLV +
d d γSV γLV
)
(2)
From eqs 1 and 2 results: interactions of the three interfaces. These data can be used to estimate the surface tension of a solid. Calculations based on these measurements give several parameters (surface free energy, adhesion work, interfacial solid−liquid tension, etc.),
p p d d γLV(1 + cos θ ) = 2 γSV γLV + 2 γSV γLV
(3)
The surface energy can be given as: 12348
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interfacial tension will be and the less spreading of the liquid over the solid surface.38 3.3. Critical Micelle Concentration. The critical micelle concentration (CMC) can be determined by carrying out surface tension measurements. Like surfactants, these polymers exhibit a specific surface tension curve as a function of the concentration. Before reaching the CMC, the surface tension changes strongly with the concentration of the polymer.41 After reaching the CMC, the surface tensions remain relatively constant or changes with a lower slope. Subsequently, the CMC was determined from the intersection of the two lines fitted through the data points. In Figure 5, the plots of the surface tension versus the concentration of the polymers are shown.
(4)
The surface-free energy values (γSV) as well as the polar (γpSV) and dispersive (γdSV) components were obtained according to the Owens−Wendt−Rabel and Kaelbe methods.36
(
d d γSV γLV +
Wa = 2
p p γSV γLV
)
(5)
where Wa is the work of adhesion. In the present work, the contact angles were measured on the dry polyurethane surfaces using four liquids: double distilled water, ethylene glycol, diiodomethane, and 1-octanol. Table 3 shows the water contact angle results, and it is observed that the contact angle values are different for the synthesized polyurethane. Table 3. Surface Parameters of the Polyurethanes γSV, mN m−1
γpSV, mN m−1
γdSV, mN m−1
γSL, mN m−1
sample
θ, deg
Wa, mN m−1
PUHDI PULDI PUIPDI
102.51 ± 0.6
57.03
14.75
3.09
11.66
30.52
101.87 ± 0.7
57.82
15.14
3.2
11.94
30.12
112.22 ± 0.5
45.26
16.12
0.32
15.79
43.65
a
a
Each value is expressed as mean ± standard error.
According to these data, the PU-IPDI has a higher value of the contact angle, indicating that the surface is enriched in hydrophobic domains. This phenomenon can be explained by the fact that the polymer surfaces are dynamic and the macromolecules from the surface can change their conformation depending on the environment. Thus, the macromolecules change their conformation, and in contact with the air they have a minimum energy.37,38 Because of the structure of the IPDI, which is more rigid than the other two, the molecules from the surfaces cannot easily change their conformations. Also, the stereo configurations of this diisocyanate limit the linearity in the polymer chain. The values of the contact angles of the polyurethanes, which have in the structure other diisocyanates, HDI and LDI, are almost the same (102°, 101°, respectively). On exposure to polar liquids, the polymers will rotate so that the hydrophilic groups are pointing toward the polar phase. This increases the wettability of the solid surface. Surface free energy was determined according to Owens− Wendt−Rabel and Kaelbe method36 using the contact angles values shown in Table 3. The results revealed that the surface free energy increases with the contact angles values. The calculations of dispersive (γdSV) and polar (γpSV) components of surface free energy can give us more information on the surface properties of the polyurethanes. As can be observed, the dispersive components increase, and the polar components of surface energy decrease (Table 3). This phenomenon is due to the fact that any increase in contact angle values leads to an increase in surface energy.39 The work of adhesion has higher values at the PU-HDI and PU-LDI because the polar components increase contrary to dispersive components.40 The interfacial solid−liquid tension has higher values at the PUIPDI (43.65 mN/m). The values of the interfacial tension could be high or low, depending on the attractive forces between the molecules in the liquid and the solid. The lower is the attraction between the liquid and the solid, the higher the
Figure 5. Surface tension versus concentration for polyurethanes.
From these plots, we can observe that the PU-HDI selfassemble into micelles at a lower CMC of 3.16 × 10−7 mol L−1, and the CMC of the PU-IPDI is 5.09 × 10−7 mol L−1 (Table 2). The CMC of the PU-LDI is 3.95 × 10−7 mol L−1. As compared to the CMC of Pluronic (4.4 × 10−6 mol L−1),42 our synthesized polymers have a lower critical micelle concentration. Also, it is know from the literature43 that the lower is the CMC value of a given amphiphilic polymer, the more stable are the micelles. PU-HDI forms micelle at the lowest concentration because this polymer has a crystalline structure (FTIR characterization), and also the gel is stronger as will be seen from rheological measurements. It has been demonstrated that the micellar stability increases with the length of the hydrophobic segment and the overall hydrophobicity of the amphiphile.27 In our case, the hydrophobicity is given by both the polyester used in synthesis (PILD) as well as the aliphatic diisocyanates. Because the quantity of PILD is the same in all of the synthesized polymers, the properties are influenced only by diisocyanate structures. The CMC is very important for biomedical applications, because micelles with a high CMC value may dissociate into unimers, and their content may precipitate in the blood.43 3.4. Thermoreversible Gelation of the Polyurethane/ Water Systems. Dynamic rheology is a powerful tool to investigate the gelation process and the microstructural changes of the material, as it allows properties to be probed as in at rest conditions without disruption of the sample microstructure.44−46 To investigate the influence of diisocyanate on the 12349
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only 3 orders of magnitude in the same temperature interval, when the loss tangent tends to a minimum value. When G′ = G″ and tan δ = 1, a first crossover point is observed, and it is a characteristic for each polymer structure. Practically, this point represents the sol−gel transition temperature, which was located at the following values: 22, 23, and 20 °C for PUHDI, PU-LDI, and PU-IPDI samples, respectively. A second crossover point of the viscoelastic parameters is observed around 54 °C, when the gel “melts” and the gel−sol transition occurs. Between these two transition temperatures, G′ > G″ and tan δ < 1. For PU-IPDI, the ratio G″/G′ is slightly lower than unity, behavior typical of a critical gel state. This phenomenon is due to the structural rigidity and steric nonregularity of the IPDI structure. Thus, the three-dimensional structure of this hydrogel is formed at a lower temperature than for the other samples. Furthermore, the PU-LDI sample presents a wider temperature where the gel state exists. Depending on the polymer structure, the samples are present in the gel state in a broad range of temperatures from 20 to 50 °C, which corresponds with our interest. 3.5. Viscoelastic Behavior at 37 °C. The variation of the complex viscosity at a temperature of 37 °C is illustrated in Figure 8. At 37 °C, it can be observed that the polyurethane hydrogels in aqueous solutions reach quickly the gel state, and after the stationary state is obtained differently for the three investigated samples. Thus, the PU-HDI reaches the gel state in approximately 50 s, and after that the viscosity remains contant. For PU-LDI, the viscosity increases sharply in the first ∼50 s, and then the increase continues during the next 30 s when the stationary state is reached. This sample shows a lower viscosity than PU-HDI. The behavior is different for the PUIPDI sample; the sharp viscosity increase observed during the first 30 s is followed by a continuous decrease during the next 360 s, which indicates that the intermolecular interactions evolve in time and stabilize only after approximately 400 s. Although this polymer gelified in a shorter time, the gel is weaker, and this is due to the rigidity of the diisocyanate. After the stationary state at 37 °C was registered, the behavior of the samples in frequency sweep tests was followed (Figure 9). For the samples PU-HDI and PU-LDI, the evolution of the viscoelastic parameters is very similar, and their values are closed (as it can be clearly observed in Figures 10 and 11). As mentioned previously, the steric conformation of the isocyanate structures influences the viscoelastic parameters. Although PU-HDI has in its structure a linear diisocyanate (HDI) and PU-LDI a branched diisocyanate (LDI), the viscoelastic parameters have not been influenced. This is also confirmed by the relaxation time (5 × 10−3 s), which indicates a structuring of these networks. Only the PU-IPDI sample, having a rigid and a nonregular steric structure, behaves differently. The viscoelastic moduli present closed values, and two crossover points are registered. The relaxation time is 5 × 10−2 s and indicates a lower structuring of this network because the distance between the physical cross-link points of the network is too high. The high gel strength observed for PU-HDI and PU-LDI can be explained as a consequence of their structures. In the conditions of shear flow, the hydrogels show nearly the same dependence of the viscosity on the shear rate (γ̇), the pseudoplastic behavior being described by the following dependence: η ≈ γ̇−0.7.
thermoreversible properties, the sol−gel−sol transition of aqueous polymer solution was investigated. The rheological properties of the polyurethane hydrogels were obtained as a function of temperature or at 37 °C as a function of time or shear conditions. In Figure 6, the evolution of the complex viscosity as a function of temperature for 15% (w/w) aqueous polyurethane
Figure 6. Evolution of the complex viscosity as a function of temperature for the polyurethane hydrogels in aqueous solution.
solutions at a heating rate of 0.5 °C min−1 (1 Pa, 1 rad s−1) is illustrated. All of the samples are in sol state at low temperatures (below 15 °C), and the viscosity is less than 0.05 Pa s. By increasing the temperature above 25 °C, the viscosity shows a sharp increase by more than 3 orders of magnitude. The sharp discontinuity is associated with a very fast answer of the macromolecular chains at the thermal stimulus. This phenomenon is generally attributed to the hydrophobic interactions between the macromolecular chains, which are not strong enough to form a stable gel at low temperature. Nevertheless, with increasing temperature, the micellar interactions increase and gelation occurs, due to the micelles aggregations into a well-defined crystalline structure.18,47 It is also observed that the increase of viscosity occurs in a narrow range of temperature (around 5 °C), and then a maximum is reached, followed above 40 °C by a region where the viscosity decreases more slowly than its increase. The structure of the polyurethane influences the transition temperatures. Thus, the PU-IPDI undergoes the sol−gel and gel−sol transitions at lower temperatures as compared to the other two polyurethane samples, due to the structural rigidity and steric nonregularity of the IPDI structure. It is followed by PU-HDI, which has a linear structure of the diisocyanate, but the viscosity of the gel is higher. On the other hand, at 37 °C, PUHDI also reaches the highest value of the viscosity. A clearer image on the kinetics of thermal-induced gelation is obtained by monitoring the variation of viscoelastic material functions, that is, the elastic (G′) and the viscous (G″) moduli and the loss tangent (tan δ) (Figure 7). In this figure, it is observed that all polyurethane samples present a liquid-like behavior at low temperatures when G″ > G′ and tan δ is high. Around the gelation point, these parameters change abruptly, and the gel state is rapidly reached. G′ increases faster than G″, and its value increases with 5 decades in magnitude. For G″, the registered increase is smaller, 12350
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Figure 7. Evolution of the viscoelastic parameters as a function of temperature for the polyurethane hydrogels (heating rate: 0.5 °C min−1, 1rad s−1, 1 Pa).
contributions. By following the recovery phase after the release of the applied stress, one can separate the total strain into the instantaneous elastic part, the recovered elastic part, and the permanently viscous part. In a creep test, a constant stress (τ) is assigned and the timerelated strain (γ) is measured. This can be expressed by the following relationship: γ (t ) = J (t ) · τ
(6)
Viscoelastic creep data can be presented by plotting the creep modulus (constant applied stress divided by total strain at a particular time) or the strain, as a function of time. Figure 12 shows the curves that represent the viscoelastic response at an applied stress of 5 Pa for the three hydrogels obtained at 37 °C, in a creep test followed by recovery. The creep curves comprise three parts: the instantaneous strain, the retardation strain, and the viscous strain. When the applied stress is removed, the recovery process starts, and first the instantaneous strain is recovered, then the retardation one, and finally remains the viscous part. The high elasticity of the hydrogels based on PU-HDI can be observed, where the reached strain after the stress of 5 Pa was applied for 60 s is very high, and the recovered strain represents 52% from the maximum value reached by the strain in the creep test, while for PU-LDI and PU-IPDI this represents 42% and 37%, respectively.
Figure 8. Evolution of the complex viscosity as a function of time for the polyurethane samples (37 °C, 1 rad s−1, 1 Pa).
Creep and recovery tests allow the differentiation between viscous and elastic responses when the viscoelastic material is subjected to a step constant stress (creep) and then the applied stress is removed (recovery). During the creep test, the stress causes a transient response, including the elastic and the viscous 12351
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Figure 9. Evolution of the viscoelastic parameters as a function of the oscillation frequency for (a) PU-HDI, (b) PU-LDI, and (c) PU-IPDI (37 °C, 1 Pa).
Figure 10. Elastic modulus for the hydrogels obtained at 37 °C.
Figure 11. Flow curves for the hydrogels obtained at 37 °C.
4. CONCLUSIONS In this study, thermoreversible polyurethane hydrogels based on poly(isopropyl lactate)diol, with gelation point near body
temperature, were synthesized and characterized. The influence of the chemical structure of diisocyanate on the polyurethane properties was studied. The crystallinity of these polyurethanes decreases in the following order: PU-HDI < PU-IPDI < PU12352
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Figure 12. Creep (open symbols) and recovery (full symbols) curves for the hydrogels at 37 °C when a stress of 5 Pa was applied for 60 s.
LDI, as seen from the FT-IR analysis. The diisocyanate structures decrease the CMC values of studied hydrogel polyurethanes as compared to the Pluronic. Also, the hydrophobic/hydrophilic balance of the polymer surfaces is due to the structure of the diisocyanate used in synthesis. The surface of the PU-IPDI is more hydrophobic, because the contact angle value is high. These polyurethane hydrogels can undergo sol−gel transitions in aqueous environment, when the polymer chains are connected together to form some physical networks by different kinds of physical forces, such as hydrogen bonds, electrostatic attraction, van der Waals forces, hydrophobic interactions, etc. The gelation temperature is near body temperature (20−23 °C), and the gelation time is very short (seconds), so that can be used in different biomedical applications. The sol−gel−sol transitions, the viscoelastic parameters (G′, G″, tan δ), as well as the gelation time are influenced by the chemical architecture of the diisocyanates. All of these properties allow them to be easily used in different industrial applications in the biomedical field. Future work will focus on the study of proteins, enzymes, or drugs delivery from these polyurethane hydrogels.
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AUTHOR INFORMATION
Corresponding Author
*Tel.: +40232-217454. Fax: +40232-211299. E-mail: gradinaru.
[email protected]. Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by a Seventh Framework Programme, NMP-2007-2.3-1, BIOSCENT, No. 214539/01.01.2009, and a grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-ID-PCE2011-3-0199 (contract 300/2011).
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