Fabrication of rapidly-responsive switches based on the coupling effect of polyacrylamide and poly(acrylic acid) without IPN structures

Abstract

Interpenetrating polymer network (IPN) structures have been applied in stimuli-responsive drug delivery systems. However, these structures may restrict the stimuli-responsive speed. In this paper, the traditional IPN structure was not applied and a novel coupling system, comprising two different polymers, polyacrylamide (PAAM) and poly(acrylic acid) (PAAC), immobilized onto different membranes, was studied for the first time. The formation and microstructures of the immobilizing membranes were investigated systematically by XPS and SEM. The thermoresponsive characteristics of the coupling membrane systems were investigated by tracking the diffusional permeability of NaCl at temperatures from below the upper critical solution temperature (UCST) to above the UCST. The results show that PAAM and PAAC were successfully immobilized onto the porous N6 membrane substrates. The proposed systems have positive switch effects with higher responsive speeds under the same conditions. The data provide valuable guidance for increasing thermoresponsive speeds and the design and preparation of new thermoresponsive switch membrane systems for different applications.

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Introduction

Environmental stimuli-sensitive polymeric systems exhibit volume or phase transitions in response to slight environmental changes such as temperature,^1–10 pH,^2,9,11–14 glucose concentration,^15–17 ethanol concentration¹⁸ and different ions and molecules.^9,19–25 They have attracted widespread interest in the last two decades due to their potential applications in numerous fields, including drug delivery, chemical separation, sensing and catalysis. As there are many cases in which environmental temperature fluctuations occur naturally, and in which the environmental temperature stimuli can be easily designed and artificially controlled, thermosensitive hydrogels or microgels have been the focus of much attention.

An important aim is to improve the thermoresponsive speeds of thermosensitive systems²⁶ because slow response speeds to temperature limit their applications in many fields, such as “smart” actuators and on–off switches. Several strategies^27–31 to increase responsive dynamics have been explored.

It is well known that polyacrylamide (PAAM) and poly(acrylic acid) (PAAC) with interpenetrating polymer network (IPN) structures can form polycomplexes in solution through hydrogen bonding.^10,26 When the environmental temperature is lower than the upper critical solution temperature (UCST) of PAAM/PAAC, the two polymer chains exhibit a so-called chain–chain zipper effect or intermolecular hydrogen bonds, which result in the IPN structures adopting shrunken states. On the other hand, when the environmental temperature is higher than the UCST, the intermolecular hydrogen bonds between PAAC and PAAM dissociate, and the IPN structure keeps a swollen state due to the relaxation of the two polymer chains. Consequently, when the temperature increases from below the UCST to above the UCST, the membrane pores change from “open” to “closed”,¹⁰ while the state of the microspheres changes from shrunken to swollen.²⁶

As shown in refs 10 and 26, the responsive range to temperature based on PAAM/PAAC with the IPN structure is about 10 °C. However, this range indicates that the thermoresponsive speed is relatively slow compared with the responsive range of poly(N-isopropylacrylamide), another thermoresponsive polymeric material (about 4 °C).²⁷

Our groups thought that the IPN structure might restrict the thermoresponsive speed, while it can also increase the mechanical strength. In this project, the traditional IPN structure was broken and the zipper effect of PAAC and PAAM was utilized. Firstly, the polymers PAAC and PAAM were immobilized on the surfaces of porous nylon 6 (N6) membranes. Then, the two immobilizing membranes were brought into close contact. We hoped that when the environmental temperature was lower than the UCST, the PAAC chains would form intermolecular hydrogen bonds with the PAAM chains. The entanglement between the two polymers would make a coupling membrane system in a closed state. However, when the environmental temperature was higher than the UCST, the intermolecular hydrogen bonds between the PAAM chains and PAAC chains would be disrupted and the coupling effect between the two polymers would no longer exist, which would put the proposed system in an open state. A schematic illustration of the proposed positively thermoresponsive switch membranes is shown in Fig. 1. The object of this project was to obtain some guidance for higher thermoresponsive speeds and to design and prepare thermoresponsive delivery systems with desired response temperatures for different applications. To our knowledge, this is the first report to break the traditional IPN structure and study the coupling effect.

Fig. 1 Schematic illustration of the concept of the proposed positively thermoresponsive switch membranes.

Experimental

Materials

Porous N6 membranes were used as the flat membrane substrates. The N6 substrates, with pore sizes of 0.22 μm, were supplied by the Xidoumen Membrane Co. Ltd, China. The acrylamide (AAM), acrylic acid (AAC), sodium hydroxide (NaOH), formic acid and ammonium cerium(IV) nitrate ((NH₄)₂Ce(NO₃)₆), as an initiator, were provided by the Sinopharm Chemical Reagent Co., Ltd, China. The AAM was used after purification by recrystallization in hexane and acetone and drying in vacuo at room temperature. The AAC was used after vacuum distillation. The N,N′-methylene bisacrylamide (BIS), as a cross-linker, was supplied by the Changsha Oumay Biotech Co., Ltd, China. Sulfuric acid (H₂SO₄) was supplied by the Kaifeng Dongda Chemical Co., Ltd, China. Other reagents were all analytical grade and used without further purification. The water used in the experiment was ultrapure water, and its resistance was 18 MΩ.

Preparation of polyacrylamide (PAAM) solution or poly(acrylic acid) (PAAC) solution

To investigate the effect of mixing PAAM solution and PAAC solution, PAAM solution and PAAC solution were prepared separately. The PAAM solution was synthesized as follows: 1 g of AAM was dissolved in 20 mL of ultrapure water and 100 mg of APS was dissolved in 5 mL of water. Nitrogen was bubbled into the two solutions to remove oxygen for 30 min. The AAM and APS solutions were then mixed. The mixture was poured immediately into 190 mL of water at 70 °C under stirring at a rate of 1000 rpm. The polymerization was carried out at 70 °C for 24 h.

The preparation of the PAAC solution used the same procedure as the PAAM solution except for changing from 1 g of AAM to 1 mL of AAC.

The optical relationship between the PAAM solution and PAAC solution

A series of mixed samples, including different volume ratios of PAAM solution and PAAC solution were obtained. All samples were put into constant-temperature baths kept at 15 to 40 °C and stored at an appointed temperature for 8 h, then photographs were taken. Finally, all photographs concerning a given sample were put together in order of increasing temperature.

Preparation of the PAAM or PAAC immobilizing membranes

In the present project, the PAAM or PAAC immobilizing membranes (N6-i-PAAM or PAAC) were prepared by applying a chemical copolymerization method. Firstly, the N6 membranes were washed with 4% (w/v) NaOH and dried to a constant weight, then the membranes were placed in 20% (w/v) formic acid solution for 2 h, then they were placed into the mixed solution including the AAM or AAC monomers, (NH₄)₂Ce(NO₃)₆/H₂SO₄ and BIS. The AAM and AAC monomer concentrations in the solution were 1 and 0.2 wt%, respectively. The weight percentage ratio of BIS to the monomer was 5 : 100. The solution was stirred and the polymerization was carried out in a constant-temperature bath at 60 °C for 4 h to obtain the immobilizing membrane. All sample membranes were immersed in ultrapure water at room temperature for 24 h to remove any unreacted monomer and homopolymer, and then were dried in oven at 40 °C overnight. The immobilizing yield of the membrane was defined as the weight increase of the membrane after the immobilizing process and could be calculated according to the equation:

Y = (m_g − m₀)/m₀ × 100% (1)

where Y stands for the immobilizing yield [%] of PAAM/PAAC on the membrane substrate, and m_g and m₀ stand for the mass [g] of the membrane after and before immobilizing, respectively.³²

Characterization of the membranes

X-ray photoelectron spectroscopy (XPS, XSAM800, Kratos, U.K.) was employed to study the composition of the membrane surface before and after immobilizing PAAM or PAAC. It used a monochromatic Al Kα X-ray source (1486.6 eV photons). The core-level signals were obtained at a photoelectron take-off angle (α, with respect to the sample surface) of 90°.

Scanning electron microscopy (SEM, Hitachi S-450, Japan) was employed to study the microscopic configuration of the N6-i-PAAM or PAAC membranes. To observe the cross-sections, the sample membranes were put into liquid nitrogen for an appropriate time, then cut with a slice and finally gilded.

Thermoresponsive diffusion experiments

The main aim of this project was to check how the thermoresponsive speed and the switch effect of the coupling system were different from that with an IPN structure. NaCl was used as a model drug and the release experiments were carried out according to a previously published method.³² To measure the permeability through the flat membrane, all membranes were dialyzed against aqueous NaCl with a known concentration for more than 3 days. All dialyses were carried out in a constant-temperature bath kept from 15 to 40 °C. The permeability of the solute across the membrane(s) was measured by determining the increase in the solute concentration of the surrounding medium with time. During the measurements, the liquid’s temperature was kept constant using a thermostatic unit. The concentration of NaCl was determined by measuring the electrical conductance with an electrical conductivity meter.

The diffusion coefficient of the solute across the flat membrane, D, can be calculated using the following equation, derived from Fick’s first law of diffusion:³²

D = −VL ln[1 − 2(C₂)_t/(C₁)₀]/(2At) (2)

where D is the diffusion coefficient [cm² s⁻¹], (C₁)₀ and (C₂)_t are the initial and intermediary concentrations (at time t) of the solute in the donor and receptor compartments, respectively [mol L⁻¹], V is the volume of liquid in the donor compartment and that in the receptor compartment [cm³], L is the thickness of the dry membrane [cm] and A is the effective diffusion area of the membrane [cm²].

Results and discussion

Thermoresponse of the mixtures including PAAM solution and PAAC solution

Fig. 2 displays the optical photographs of the mixtures containing different volume ratios of PAAM solution and PAAC solution at different temperatures. From these photos, the transmittance of all mixtures is shown to change from turbid to clear with increasing temperature. This is because when the environmental temperature was lower than the UCST of PAAM/PAAC, the two polymer chains linked together by intermolecular hydrogen bonds, which resulted in the dramatic scattering of light and the mixtures displaying turbidity. On the other hand, when the environmental temperature was higher than the UCST, the intermolecular hydrogen bonds between PAAC and PAAM dissociated, and the two polymer chains relaxed, which made the mixtures weakly scatter light and display as clear. The results verified that the mixed solutions including the two polymer chains were thermoresponsive and that the two polymer chains formed intermolecular hydrogen bonds like those of the IPN structure.

Fig. 2 The optical photographs of the mixtures including PAAM solution and PAAC solution at different temperature.

Immobilizing yields of the sample membranes

A series of the PAAM or PAAC immobilizing membranes were prepared by controlling the monomer concentrations and the reaction time. To study the effects of the immobilizing yield and the ratio of the immobilizing yield (R = Y_PAAC/Y_PAAM) of the coupling membranes on the thermoresponsive switch characteristics, two types of coupling membrane with the same R were chosen and are listed in Table 1.

Table 1 The immobilizing yields and the ratio of the immobilizing yields (R) of the different types of the coupling membranes

Number of the coupling membrane	YPAAC [%]	YPAAM [%]	R	The type of the coupling membrane
a When the diffusional solute went across the immobilizing-PAAC membrane and then the immobilizing-PAAM membrane, this type of coupling membrane was assigned as C–M, otherwise it was assigned as M–C.
a	—	—	—	Single virgin membrane
b	5.47		—	Single membrane
c		6.43	—	Single membrane
d	—	—	—	Double virgin membranes
e	5.47	6.43	0.85	C–M^a
f	5.47	6.43	0.85	M–C^a

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The chemical characterization and morphological analysis of the N6-i-PAAM or PAAC membrane

Fig. 3 shows the XPS O1s core-level spectra of the virgin N6 membrane, the immobilizing-PAAM membrane and the immobilizing-PAAC membrane. The peak areas representing the binding energy of the C=O species (531.2 eV) were compared for the virgin N6 membrane and the immobilizing-PAAM membrane (52 844.6 and 57 152.9, respectively) and the difference between the peak areas confirmed that PAAM had been successfully immobilized onto the porous N6 membrane substrate. A comparison of the binding energies for the C=O species and O–H species between the virgin N6 membrane and the immobilizing-PAAC membrane (531.0 eV and 532.2 eV, respectively) proved that PAAC had been successfully immobilized onto the porous N6 membrane substrate.

Fig. 3 XPS O1s core-level spectra of (a) the virgin N6 membrane, (b) the immobilizing-PAAM membrane and (c) the immobilizing-PAAC membrane.

The SEM images of the cross sections of the virgin porous N6 substrate, immobilizing PAAM membrane and immobilizing PAAC membrane are shown in Fig. 4. By comparing the inner pore surfaces and thicknesses near the membrane surface of the virgin substrate (Fig. 4a) with the immobilizing-PAAM membrane (Fig. 4b) and immobilizing-PAAC membrane (Fig. 4c), the changes in the microstructures indicated that PAAM and PAAC had been successfully immobilized onto the porous N6 membrane substrates, respectively.

Fig. 4 SEM micrographs of the cross sections of (a) the virgin N6 membrane, (b) the N6-i-PAAM membrane (Y_PAAM = 6.43%) and (c) the N6-i-PAAC membrane (Y_PAAC = 5.47%). Scale bar = 5 μm.

Thermoresponsive diffusional permeability of the coupling systems

Fig. 5a–f show the diffusional dynamics of the model drug permeating through the virgin N6 substrate membrane, the immobilizing-PAAM membrane, the immobilizing-PAAC membrane, two virgin N6 substrate membranes and the coupling membranes at a different temperature. The diffusional coefficient of the drug permeating through the single substrate membrane (as shown in Fig. 5a) increases simply with increasing environmental temperature in the range of 15–40 °C. The diffusional coefficients of the drug permeating through the immobilizing-PAAM or -PAAC membranes (as shown in Fig. 5b and c) were also simple, which means that the singly-immobilizing membranes had no thermoresponsive character because PAAM or PAAC alone had no sensitivity to the temperature. The reason for the diffusional coefficients increasing was only because of the thermal motion resulting from the increasing temperature.

Fig. 5 Effect of temperature on the permeation of NaCl through different membrane(s) with PAAC or PAAM switches. (a) The virgin N6 membrane. (b) The N6-i-PAAC membrane (Y_PAAC = 5.47%). (c) The N6-i-PAAM membrane (Y_PAAM = 6.43%). (d) Two virgin N6 membranes. (e) The C–M coupling membranes. (f) The M–C coupling membranes (Y_PAAC = 5.47% and Y_PAAM = 6.43%).

As shown in Fig. 5d, the diffusional coefficient of the drug running across two virgin membranes remained unchanged when the temperature increased from 15 to 40 °C, which indicates that this system had no thermoresponsive character. However, under the same experimental conditions, the diffusional coefficient of the drug running across the coupling membranes comprising of immobilizing-PAAM membrane and immobilizing-PAAC membrane exhibited an interesting phenomenon. The diffusional coefficient changed dramatically at temperatures around the UCST (as shown in Fig. 5e and f). These systems exhibited positive thermoresponsive characteristics, which meant that the permeabilities of these coupling membranes increased with increasing environmental temperature and were different from the membrane system with an IPN structure.¹⁰ This phenomenon demonstrated that the switch effect was in existence. The effect made the membrane systems adopt a closed state when the environmental temperature was lower than the UCST because the PAAC chains formed intermolecular hydrogen bonds with the PAAM chains. However, the systems displayed an opened state when the environmental temperature was higher than the UCST as the intermolecular hydrogen bonds between the PAAM chains-PAAC chains were being disrupted. The results testified again that the two polymers existed in a coupled relationship when the temperature was lower than the UCST.

It is also interesting that the thermoresponsive trend was obvious when the order of the immobilizing-PAAM membrane and the immobilizing-PAAC membrane was exchanged (as seen in Fig. 5e and f). A sharp transition in the permeability occurred when the temperature increased from 25 to 30 °C while the drug was running firstly across the immobilizing-PAAC membrane and then the immobilizing-PAAM membrane (as seen in Fig. 5e). While the transition range was from 20 to 35 °C when the drug was running firstly across the immobilizing-PAAM membrane and then the immobilizing-PAAC membrane (as seen in Fig. 5f). The reason may be that the immobilizing PAAC and PAAM are both swellable gels and the dilatability of PAAC is larger than that of PAAM, although the relative investigations are still continuing. However, this transition temperature range (5 °C) suggested the responsive speed to temperature was higher than that of a system with the IPN structure under the same conditions,^10,26 which means that our previous speculation is reasonable.

Conclusions

In summary, a novel family of thermoresponsive switch membranes comprising an immobilizing-PAAM membrane and an immobilizing-PAAC membrane have been successfully developed. These systems did not adopt the traditional IPN structure of PAAM and PAAC and exhibited their coupling effect through intermolecular hydrogen bonds. The XPS and SEM results show that PAAM and PAAC were successfully immobilized onto the porous membrane substrates. The diffusional permeabilities of the coupling systems exhibited significantly positive switch characteristics and higher thermoresponsive speeds than those with an IPN structure under the same conditions. The coupling membranes provide a new mode of behavior for thermoresponsive “smart” or “intelligent” membrane actuators, which are highly attractive for targeting delivery systems, chemical separations and sensors.

Acknowledgements

This work was funded by the National Natural Science Foundation of China (21276287, 20976202) and the Academic Team of the South-Central University for Nationalities (XTZ15013, CZW15017).

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