Article pubs.acs.org/Langmuir
Schizophrenic Core−Shell Microgels: Thermoregulated Core and Shell Swelling/Collapse by Combining UCST and LCST Phase Transitions Jun Yin,*,† Jinming Hu,‡ Guoying Zhang,‡ and Shiyong Liu*,‡ †
Key Laboratory of Advanced Functional Materials and Devices, Anhui Province, Department of Polymer Material and Engineering, School of Chemical Engineering, Hefei University of Technology, Hefei 230009, China ‡ CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China S Supporting Information *
ABSTRACT: A variety of slightly cross-linked poly(2-vinylpyridine)−poly(N-isopropylacrylamide) (P2VP−PNIPAM) core− shell microgels with pH- and temperature-responsive characteristic were prepared via seeded emulsion polymerization. Negatively charged sodium 2,6-naphthalenedisulfonate (2,6-NDS) could be internalized into the inner core, followed by formation of (P2VPH+/SO32−) supramolecular complex through the electrostatic attractive interaction in acid condition. The thermoresponsive characteristic feature of the (P2VPH+/SO32−)−PNIPAM core−shell microgels was investigated by laser light scattering and UV−vis measurement, revealing an integration of upper critical solution temperature (UCST) and lower critical solution temperature (LCST) behaviors in the temperature range of 20−55 °C. The UCST performance arised from the compromised electrostatic attractive interaction between P2VPH+ and 2,6-NDS at elevated temperatures, while the subsequent LCST transition is correlated to the thermo-induced collapse of PNIPAM shells. The controlled release of 2,6-NDS was monitored by static fluorescence spectra as a function of temperature change. Moreover, stopped-flow equipped with a temperature-jump accessory was then employed to assess the dynamic process, suggesting a millisecond characteristic relaxation time of the 2,6-NDS diffusion process. Interestingly, the characteristic relaxation time is independent of the shell cross-link density, whereas it was significantly affected by shell thickness. We believe that these dual thermoresponsive core−shell microgels with thermotunable volume phase transition may augur promising applications in the fields of polymer science and materials, particularly for temperature-triggered release.
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been studied.7−10 Contrary to the well-known LCST micelles, UCST micelles will form when the temperature is below a critical temperature and disassemble when the temperature is above it. Recent reported UCST systems include the assemblies fabricated from zwitterionic block copolymers or formed in organic solvent driven by H-bonding between synthetic or biological copolymers.11−16 In addition, UCST systems can be also constructed by complementary multivalent cross-linkers,
INTRODUCTION
The design and synthesis of soft materials capable to respond to external stimuli is one of the most attractive fields in polymer chemistry.1,2 Water-soluble polymeric materials have been a tremendous research focus in academic and applied polymer science over the past decades because of their drastic property responsibility upon small changes of external stimuli, such as temperature or pH.3−6 Thermoresponsive polymers can exhibit change in hydrophilicity upon heating or cooling. Polymeric micelles with a lower critical solution temperature (LCST) behavior or an upper critical solution temperature (UCST) behavior have © 2014 American Chemical Society
Received: January 11, 2014 Revised: February 20, 2014 Published: February 20, 2014 2551
dx.doi.org/10.1021/la500133y | Langmuir 2014, 30, 2551−2558
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Scheme 1. Schematic Illustration of the Reversible Thermoresponsive Volume Phase Transition of P2VP−PNIPAM Core−Shell Microgels at Low pH as Well as Its Thermo-Induced Uptake and Release of 2,6-NDS in Aqueous Dispersion
such as multivalent ions.10,17,18 For example, core−shell UCST micelles derived from the ionic cross-linking of PEO-b-P2VPH+ by S2O82− in water were reported by Chen et al., and the complex formation and thermal induced dissociation are reversible.17 Similarly, Shi and Zhu et al. studied SO42−induced micellization of PEG-b-P4VPH+ and demonstrated their corresponding responsiveness was also thermoreversible.18 Such complexes share the same features that are sensitive to the variation of environmental parameters that affect electrostatic interactions. Moreover, the responsibility of these cross-linking of oppositely charged polymers/multivalent ions cross-linkers (S2O82− or SO42−) is thermoreversible. Although the temperature dependence of the structure of micellar complexes is of both theoretical and practical significance and UCST behaviors are expected to be very promising in applications, only a few systems with unique UCST performances are exploited thus far. Microgels are of mounting interest and extensively studied because of their speedy responses to external stimuli, which has spurred potential applications in a number of fields.19−21 In contrast to the conventional microgels exhibiting LCST behaviors in aqueous solution, microgels bearing UCST phase transition behavior are scarce. Recent reported examples are mainly involved in the self-assembly of copolymers in aqueous solution via H-bonding or electrostatic interactions, termed as UCST-like microgels.22−25 For instance, temperature-inert polyacrylamide (PAAm) can be conferred unexpected UCST performance in the presence of poly(acrylic acid) (PAA).22 The microgels are in collapsed states when temperature is lower than the UCST, while it undergoes disintegration upon heating the solution over UCST due to the breakdown of the hydrogen bonding between PAAm and PAA. Additionally, a UCST thermal phase transition could also be observed at lower temperatures for moderately cross-linked core−shell nanogel particles obtained from self-assembly in aqueous solution of double hydrophilic block copolymers.26 Besides the UCST transition, LCST that determined the micelle-to-nanogel transition was also observed at elevated temperatures. It should be noted that such micro- or nanogels are distinctly different from the classical cross-linked stimuli-
responsive microgels, and no UCST behavior will be retained if these interpolymer complexes are too stable to be decomplexed by raising the temperature.17 Inspired by above aspects concerning water-soluble polymeric materials with UCST transition behaviors, we attempted to synthesize true microgel-based thermoresponsive smart materials with both UCST and LCST properties. Although You et al. had reported a block copolymer with tunable LCST and UCST behavior by adjusting the fraction of oligo(ethylene glycol) methacrylate (OEGMA) units in the random copolymer and selective quaternization of poly(N-(3(dimethylamino)propyl)methacrylamide) (PDMAPMA) block using 1,3-propane sultone, respectively,9 microgel-based double thermoresponsive materials with both of UCST and LCST are less explored. Herein, we encapsulated cross-linked poly(2vinylpyridine) (P2VP) cores inside a series of cross-linked poly(N-isopropylacrylamide) (PNIPAM) shell with varying cross-linking density and thickness to form P2VP−PNIPAM core−shell microgels using seeded emulsion polymerization. Once in acid solution, the swollen protonated P2VP core (P2VPH+) absorbed negatively charged sodium 2,6-naphthalenedisulfonate (2,6-NDS), a hydrophilic fluorescein with two SO32− groups, into the microgel interior to form (P2VPH+/ SO32−) complex with a tunable UCST behavior owing to electrostatic attractive interactions between 2,6-NDS and P2VPH+ core. PNIPAM is well-known to display strong collapsed tendency upon heating when the LCST is approached (∼32 °C).27−29 The dispersion properties of such core−shell microgels and their uptake and release of 2,6-NDS ability were systematically studied as a function of temperature changes by LLS, UV−vis, fluorescence, and stopped-flow techniques. These microgel carriers possessing both tunable UCST and LCST, accompanied by significant fluorescence variation, endow them a potential highly drug loading system and render an easy, flexible, and effective strategy for the controlled release, as indicated in Scheme 1.
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EXPERIMENT PART
Materials. N-Isopropylacrylamide (NIPAM, 97%, Tokyo Kasei Kagyo Co.) was purified by recrystallization from a mixture of benzene 2552
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samples for SEM observations were prepared by placing 20 μL of microgel dispersion on copper grids successively coated with thin films of Formvar and carbon. Potentiometric Titrations. The core−shell P2VP−PNIPAM microgels were first dispersed in deionized water and then titrated to pH 10.0. This dispersion was titrated by the dropwise addition of 0.1 M HCl, and the solution pH was monitored with a Corning Check-Mite pH meter (precalibrated with pH 4.0, 7.0, and 10.0 buffer solutions). UV−vis Transmittance Measurements. The optical transmittance of the aqueous dispersion of microgels was acquired on a Unico UV− vis 2802PCS spectrophotometer and measured at a wavelength of 700 nm using a thermostatically controlled cuvette. Fluorescence Measurements. Fluorescence spectra were recorded using a RF-5301/PC (Shimadzu) spectrofluorometer. The temperature of the water-jacketed cell holder was controlled by a programmable circulation bath. The slit widths were set at 5 nm for excitation and 5 nm for emission. Laser Light Scattering (LLS). A commercial spectrometer (ALV/ DLS/SLS-5022F) equipped with a multitaudigital time correlator (ALV5000) and a cylindrical 22 mW UNIPHASE He−Ne laser (λ0 = 632 nm) as the light source was employed for dynamic LLS measurements. Scattered light was collected at a fixed angle of 90° for duration of 5 min. Distribution averages and particle size distributions were computed using cumulants analysis and CONTIN routines. All data were averaged over three consecutive measurements. Stopped-Flow Measurements. Stopped-flow studies were carried out using a Bio-Logic SFM300/S stopped-flow instrument. It is equipped with three 10 mL step-motor-driven syringes (S1, S2, and S3), which can be operated independently to carry out single- or double-mixing. The stopped-flow device is attached to a MOS-250 spectrometer; kinetic data were fitted using the Biokine program provided by Bio-Logic. The excitation and emission wavelengths were adjusted to 268 and 330 nm, respectively, with 10 nm slits. Using FC08 or FC-15 flow cells, typical dead times are 1.1 and 2.6 ms, respectively. The solution temperature was maintained at 15 °C by circulating water around the syringe chamber and the observation head. Prior to loading into the motor-driven syringes, all aqueous solutions were clarified by passing through 2.0 μm Millipore Nylon filters. The millisecond temperature jump (mT-jump) accessory is equipped with a standard Bio-Logic stopped-flow observation cell; three thermoelectric Peltier elements are used to control the initial temperatures of the two solutions and that of the observation cell after mixing. The temperature of the mixed solution was calibrated to be the same as the observation cell (Peltier controlled) with the aid of a thermosensitive fluorescent dye, N-acetyl-L-tryptophanamide (NATA). The precision of the temperature jump is within ±0.1 °C, and the temperature stability in the observation cell after temperature jump was
