polymers Article
Thixotropic Supramolecular Pectin-Poly(Ethylene Glycol) Methacrylate (PEGMA) Hydrogels Siew Yin Chan 1,2 , Wee Sim Choo 1, *, David James Young 1,2,3, * and Xian Jun Loh 2,4,5, * 1 2 3 4 5
*
School of Science, Monash University Malaysia, Subang Jaya 47500, Malaysia;
[email protected] Institute of Materials Research and Engineering (IMRE), A*STAR (Agency for Science, Technology and Research), Singapore 138634, Singapore Faculty of Science, Health, Education and Engineering, University of the Sunshine Coast, Sunshine Coast, QLD 4558, Australia Department of Materials Science and Engineering, National University of Singapore, Singapore 117576, Singapore Singapore Eye Research Institute, Singapore 168751, Singapore Correspondence:
[email protected] (W.S.C.);
[email protected] (D.J.Y.);
[email protected] (X.J.L.); Tel.: +60-3-5514-6114 (W.S.C.); +61-7-5456-3448 (D.J.Y.); +65-6416-8932 (X.J.L.)
Academic Editor: Alexander Böker Received: 2 October 2016; Accepted: 10 November 2016; Published: 18 November 2016
Abstract: Pectin is an anionic, water-soluble polymer predominantly consisting of covalently 1,4-linked α-D-galacturonic acid units. This naturally occurring, renewable and biodegradable polymer is underutilized in polymer science due to its insolubility in organic solvents, which renders conventional polymerization methods impractical. To circumvent this problem, cerium-initiated radical polymerization was utilized to graft methoxy-poly(ethylene glycol) methacrylate (mPEGMA) onto pectin in water. The copolymers were characterized by 1 H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA), and used in the formation of supramolecular hydrogels through the addition of α-cyclodextrin (α-CD) to induce crosslinking. These hydrogels possessed thixotropic properties; shear-thinning to liquid upon agitation but settling into gels at rest. In contrast to most of the other hydrogels produced through the use of poly(ethylene glycol) (PEG)-grafted polymers, the pectin-PEGMA/α-CD hydrogels were unaffected by temperature changes. Keywords: pectin; poly(ethylene glycol) methacrylate; cerium; α-cyclodextrin; supramolecular hydrogel
1. Introduction Pectins are complex carbohydrates derived from dicotyledonous and some monocotyledonous plants [1]. Commercially, pectins are produced from food industry waste [2]. They are mainly extracted with hot dilute mineral acid from citrus peel, apple pomace and to a smaller extent, sugar beet pulp [3,4]. Pectin is a safe food additive with no limit on acceptable daily intake. It is non-toxic, biodegradable and biocompatible [5,6]. Its applications are diverse spanning the food, pharmaceutical, cosmetic and polymer industries [7–9]. Pectins are primarily utilized as emulsifiers, gelling agents, glazing agents, stabilizers or thickeners [10]. This family of polysaccharides consists of galacturonic acid (GalA) units covalently-linked by α-(1→4) glycosidic bonds and are classified according to the degree of methylation (DM). DM is defined as the molar ratio of methyl-esters present relative to the total moles of GalA units. It is the major parameter affecting gelling [11]. Pectins are classified as either high methoxy pectin (HMP) with a DM > 50% or low methoxy pectin (LMP) with a DM < 50%. HMP gels in high co-solute concentration
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with acid through a combination of hydrophobic forces and hydrogen bonding [12]. LMP gels in the presence of divalent metal cations such as calcium over a broad range of pH and the gels are formed through ionic cross-linking between free carboxylate groups in an arrangement known as the egg-box model [13]. 8, 404 2 of 12 WePolymers have2016, an interest in grafting pectin with synthetic polymers to improve its processability in organicpresence solventsofand to impart biocompatibility and biodegradability to the resulting copolymer for use divalent metal cations such as calcium over a broad range of pH and the gels are formed in biomedical applications. Herein, we free describe pectin-poly(ethylene glycol) known methacrylate (PEGMA) through ionic cross-linking between carboxylate groups in an arrangement as the eggcopolymer and subsequently generated supramolecular hydrogels by threading the poly(ethylene box model [13]. Wetendrils have anwith interest in grafting pectin with units. synthetic polymers to[14] improve processability in glycol) (PEG) α-cyclodextrin (α-CD) Harada et al. first its reported supramolecular organic solvents to impartα-cyclodextrin biocompatibility toroids and biodegradability resulting copolymer for hydrogel formed by and threading onto PEG to ofthe high molecular weight. This use in biomedical applications. Herein, we describe pectin-poly(ethylene glycol) methacrylate PEG-graft forms physical cross-linking points via the aggregation of the inclusion complexes, yielding (PEGMA) copolymer and subsequently generated supramolecular hydrogels by threading the supramolecular hydrogels [15–19]. poly(ethylene glycol) (PEG) tendrils with α-cyclodextrin (α-CD) units. Harada et al. [14] first reported Pectin is a hydrophilic insoluble in all organic polymerization supramolecular hydrogelpolymer formed byand threading α-cyclodextrin toroids solvents. onto PEG ofMost high molecular weight. This PEG-graft forms physical points via the aggregation of the inclusion methods require organic solvents, making cross-linking it a challenge to graft pectin with synthetic polymers. We yielding supramolecular hydrogels [15–19]. reaction in water to graft PEGMA onto pectin have forcomplexes, the first time utilized a redox polymerization Pectin is a hydrophilic polymer and insoluble in all organic solvents. Most polymerization and have thereby generated pectin supramolecular gels with unique rheology. methods require organic solvents, making it a challenge to graft pectin with synthetic polymers. We have for the first time utilized a redox polymerization reaction in water to graft PEGMA onto pectin 2. Materials and Methods and have thereby generated pectin supramolecular gels with unique rheology.
Ammonium cerium (IV) sulfate dihydrate, apple pectin and sodium nitrate were purchased from 2. Materials and Methods Sigma-Aldrich, Singapore, Singapore. Methoxy-poly(ethylene glycol) methacrylate (mPEGMA) with Ammonium (IV) sulfate from dihydrate, apple Xiamen, pectin andChina. sodium α-Cyclodextrin nitrate were purchased Mn of 10,000 g·mol−1 cerium was purchased Sinopeg, (α-CD) was fromfrom Sigma-Aldrich, Singapore,Japan. Singapore. (mPEGMA) purchased TCI, Kawaguchi, All Methoxy-poly(ethylene reagent and solventsglycol) were methacrylate used as received. with Mn of 10,000 g·mol−1 was purchased from Sinopeg, Xiamen, China. α-Cyclodextrin (α-CD) was purchased from TCI, Kawaguchi, Japan. P-10K All reagent and solvents were used as received. 2.1. Synthesis of Pectin-PEGMA Copolymer,
2.1. Synthesiscerium of Pectin-PEGMA Copolymer, P-10K(0.005 M, based on the final volume of solution) was Ammonium (IV) sulfate dihydrate added into aAmmonium pectin solution (1% w/v in water). stirred at room cerium (IV) sulfate dihydrate The (0.005solution M, basedwas on the final volume of temperature solution) was for 2 h. added into a pectin (1% w/vThe in water). The mixture solution was at room temperature for 2 h.for 48 h. mPEGMA (1% w/v) wassolution then added. reaction wasstirred stirred at room temperature mPEGMA w/v) and was then added. Themixture reaction mixture room temperaturewas for 48 h. Chloroform was (1% added the resulting was leftwas to stirred settle.atPectin-PEGMA obtained in Chloroform was added and the resulting mixture was left to settle. Pectin-PEGMA was obtained in 61.5% yield by precipitating the white emulsion layer in hexane followed by drying under vacuum at 61.5% yield by precipitating the white emulsion layer in hexane followed by drying under vacuum 40 ◦ C. The mechanism of cerium-initiated radical polymerization is shown in Figure 1. at 40 °C. The mechanism of cerium-initiated radical polymerization is shown in Figure 1.
Figure 1. Mechanism of cerium-initiated radical polymerization.
Figure 1. Mechanism of cerium-initiated radical polymerization.
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2.2. Polymer Characterisation 1H
Nuclear magnetic resonance (NMR) spectra were recorded on a JEOL 500 MHz NMR Polymers 2016, 8, 404 3 of 12 spectrometer (JEOL, Tokyo, Japan) at room temperature. The 1 H NMR measurements were carried out Polymer Characterisation with an 2.2. acquisition time of 4.37 s, a pulse repetition time of 9.37 s and a 90◦ pulse width. Measurements 1H Nuclear were done with 16 scans and chemical referred to the solvent peak = 4.79 ppm for magnetic resonance shifts (NMR) were spectra were recorded on a JEOL 500 (δ MHz NMR 1H NMR measurements were carried spectrometer Tokyo, Japan) at room temperature. The deuterium oxide, D(JEOL, O). 2 out with an acquisition time of 4.37 s, a pulse repetition time of 9.37 s and a 90° pulse width. Elmer Fourier transform infrared (FTIR) spectra of the pellet samples were recorded on a Perkin Measurements were done with 16 scans and chemical shifts were referred to the solvent peak (δ = Spectrum 2000 FTIR spectrometer (Perkin Elmer, Waltham, MA, USA); 64 scans were signal-averaged 4.79 ppm for deuterium oxide, D 2O). with a resolution of 4 cm−1 at room temperature. Pellets were prepared by coating the samples with Fourier transform infrared (FTIR) spectra of the pellet samples were recorded on a Perkin Elmer potassium bromide. Spectrum 2000 FTIR spectrometer (Perkin Elmer, Waltham, MA, USA); 64 scans were signal-averaged with a resolution of 4 cm−1 at room temperature. Pellets were prepared by coating the samples with
2.3. Thermal Analysis potassium bromide.
Thermogravimetric analysis (TGA) was performed on a TA Instruments TGA Q500 (TA Instruments, 2.3. Thermal Analysis New Castle, DE, USA). Samples were heated from room temperature to 900 ◦ C at a rate of 20 ◦ C·min−1 Thermogravimetric analysis (TGA) was performed on a TA Instruments TGA Q500 (TA under continuous nitrogen purge with a flow rate of 40 mL·min−1 . Instruments, New Castle, DE, USA). Samples were heated from room temperature to 900 °C at a rate of 20 °C·min−1 under continuous nitrogen purge with a flow rate of 40 mL·min−1.
2.4. Preparation of Pectin-PEGMA/α-CD Hydrogels
2.4. Preparation of Pectin-PEGMA/α-CD Hydrogels Solutions of α-CD in water were added into pectin-PEGMA solutions of different compositions. Solutions of α-CD in water were added intoto pectin-PEGMA solutions of different compositions. The resultant mixtures were sonicated and left stand at room temperature. Gel formation was The resultant mixtures were sonicated and left to stand at room temperature. Gel formation was α-CD observed at 24 h (Figure 2). The sol-gel transition for P-10K was determined by plotting observed at 24 h (Figure 2). The sol-gel transition for P-10K was determined by plotting α-CD concentration versus polymer concentration over the polymer to α-CD solution composition range of concentration versus polymer concentration over the polymer to α-CD solution composition range 1%–10%ofw/v, permitting determination of the critical gelation concentration. 1%–10% w/v, permitting determination of the critical gelation concentration.
Figure 2. The preparation of pectin-PEGMA/α-CD gels.
Figure 2. The preparation of pectin-PEGMA/α-CD gels. 2.5. Rheology Studies
2.5. RheologyThe Studies rheological behavior of pectin-PEGMA/α-CD gels was investigated using a Discovery DHRhybrid rheometer (TA Instruments, New Castle, DE, USA) withinvestigated flat plate geometries of DHR-3 The3 rheological behavior of pectin-PEGMA/α-CD gels was using a(diameters Discovery 20 and 40 mm) in steady and dynamic modes. All the tests were performed using a flat plate geometry hybrid rheometer (TA Instruments, New Castle, DE, USA) with flat plate geometries (diameters of with diameter of 40 mm unless otherwise stated. Amplitude sweeps were performed under 20 and 40 mm) in shear steady and dynamic modes. All thethat tests were performed a flat plate geometry oscillatory at strain of 0.01%–100% to ensure subsequent data were using collected in the linear with diameter of 40 mm unless otherwise stated. Amplitude sweeps were performed under oscillatory viscoelastic region (LVR). Frequency sweeps were then performed in the range of 0.01–50 Hz under at a strain 0.05%. that Reversibility of thedata hydrogels determined amplitude shear atoscillatory strain of shear 0.01%–100% toofensure subsequent were was collected in thebylinear viscoelastic sweeps Frequency at 2 points (0.05% and 25% strain), and 2.5 min, respectively, at each strain point, for 3 cycles. region (LVR). sweeps were then5 performed in the range of 0.01–50 Hz under oscillatory shear at a strain of 0.05%. Reversibility of the hydrogels was determined by amplitude sweeps at 2 points (0.05% and 25% strain), 5 and 2.5 min, respectively, at each strain point, for 3 cycles. All tests
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Polymers 2016, 8,at404 4 of 12 were performed 25 ◦ C (room temperature) and 37 ◦ C to mimic body temperature. Temperature sweeps were performed using a flat plate geometry with diameter of 20 mm at a strain of 0.5% and All tests were performed at 25 °C (room temperature) and 37 °C to mimic body temperature. ◦ C, with a ramp rate of 5 ◦ C·min−1 . frequency of 1 Hz sweeps in the temperature range of a10–40 Temperature were performed using flat plate geometry with diameter of 20 mm at a strain
of 0.5% and frequency of 1 Hz in the temperature range of 10–40 °C, with a ramp rate of 5 °C·min−1.
3. Results
3. Results
3.1. Synthesis and Characterization of Pectin-PEGMA Copolymer, P-10K 3.1. Synthesis andcopolymer Characterization of Pectin-PEGMA Copolymer, P-10Kpolymerization in distilled water Pectin-PEGMA (P-10K) was prepared by radical using ammonium ceriumcopolymer (IV) sulfate dihydrate as a redox Chloroform was added to extract Pectin-PEGMA (P-10K) was prepared byinitiator. radical polymerization in distilled water ammonium sulfatein dihydrate as a redox initiator. Chloroform addedmiddle to extractlayer excessusing PEGMA. Threecerium layers(IV) formed settling; cloudy brown solution, was a white excess PEGMA. Three layers formed in settling; a containing cloudy brown a white middle layer emulsion and at the bottom a transparent chloroform thesolution, unreacted mPEGMA. emulsion and at the bottom a transparent chloroform containing the unreacted mPEGMA. 1H NMR spectroscopy in D2 O was performed on the middle emulsion layer, but proved 1H NMR spectroscopy in D2O was performed on the middle emulsion layer, but proved inconclusive (Figure S1). FTIR, however, contained absorption characteristics of pectin and mPEGMA inconclusive (Figure S1). FTIR, however, contained absorption characteristics of pectin and (10KPEGMA). Pectin exhibits a broad peak at around 3450 cm−1 , arising from hydroxyl group mPEGMA (10KPEGMA). Pectin exhibits a broad peak at around − 3450 cm−1, arising from hydroxyl 1 stretching (Figure 3) [20]. Absorptions at 1750 and cm 1630 were to the carboxylic −1 were assigned group(O–H) stretching (O–H) (Figure 3) [20]. Absorptions at 1630 1750 and cmassigned to the acid and ester groups (C=O stretches) of the pectin polymers [21]. 10KPEGMA displays a broad apeak carboxylic acid and ester groups (C=O stretches) of the pectin polymers [21]. 10KPEGMA displays 1 but not as intensive around 3450peak cm−around as as forintensive pectin. The FTIR spectrum of 10KPEGMA also contained broad 3450 cm−1 but not as for pectin. The FTIR spectrum of 10KPEGMA 1 . CH (bending) −1 , CHat (bending) −1. CH2 (bending) −1 CH3 distinctive C–H stretches at 2875 cm− at 1450 cm also contained distinctive C–H stretches stretches 2 at 2875 cmstretches 3 1450 cm , stretches − 1 − 1 −1 −1 (bending) stretches at 1350 cm and cm C–O stretches 1110 cm The wereFTIR also spectrum observed. The FTIR for at 1350 cm and C–O stretches at 1110 were alsoatobserved. obtained spectrum obtained for 10KPEGMA matched those reported by Wang et al. [22] and Bagheri et al. [23]. 10KPEGMA matched those reported by Wang et al. [22] and Bagheri et al. [23].
Figure 3. FTIR spectra of the precursors(pectin (pectinand and 10KPEGMA) 10KPEGMA) and P-10K. Figure 3. FTIR spectra of the precursors andofofcopolymer copolymer P-10K.
3.2. Thermal Analysis
3.2. Thermal Analysis
Thermal stabilities of the precursors and copolymer were studied by TGA. The degradation
Thermal stabilities of the precursors and copolymer were studied by TGA. The degradation temperatures were determined from the peak of derivative weight curves and are summarized in temperatures were were determined from thetemperatures peak of derivative curves are summarized Table 1. There two degradation recorded weight for pectin; 86.33 and and 253.33 °C (Figure in ◦ C (Figure 4). Table 1. There were two degradation temperatures recorded for pectin; 86.33 and 253.33 4). The first degradation temperature corresponds to the loss of water. 10KPEGMA exhibited a The first degradation temperature corresponds to the loss ofrevealed water. 10KPEGMA exhibited a degradation degradation temperature of 413.53 °C. TGA of P-10K three degradation temperatures, ◦ C. TGA corresponding to those for pectin and mPEGMA. amount of pectin in P-10K was calculated to be temperature of 413.53 of P-10K revealedThe three degradation temperatures, corresponding around 17% (Table to those for pectin and1).mPEGMA. The amount of pectin in P-10K was calculated to be around 17% (Table 1).
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Polymers1. 2016,Decomposition 8, 404 12 Table temperatures (Td ) of the precursors (pectin and 10KPEGMA)5 of and Table 1. Decomposition temperatures (Td) of the precursors (pectin and 10KPEGMA) and copolymer copolymer P-10K.
P-10K. Table 1. Decomposition temperatures (Td) of the precursors (pectin and 10KPEGMA) and copolymer P-10K. SampleSample (◦ C) Weight change Weight(%) change (%) TTd d(°C) d86.33 (°C) Weight 8.95 change (%) T86.33 8.95
Sample
Pectin Pectin
Pectin 10KPEGMA 10KPEGMA 10KPEGMA
P-10K P-10K P-10K
253.33 86.33 253.33
8.95 80.82
80.82
418.07 253.33 418.07
80.82 99.02
99.02 5.74 16.70 62.91
418.07 85.89 85.89
99.02 5.74
240.29 85.89 240.29
5.74 16.70
240.29 421.19
421.19
16.70 62.91
421.19
62.91
Pectin 10KPEGMA Pectin P-10K 10KPEGMA P-10K
100 90 100
Weight Weight (%) (%)
80 90 70 80 60 70 50 60 40 50 30 40 20 30 10 20 0 10 0
0
100 200 300 400 500 600 700 800 900 1000
0
100 200 300 400 500 600 700 800 900 1000 Temperature (°C)
Temperature Figure 4. TGA curves of the precursors (pectin and(°C) 10KPEGMA) and copolymer P-10K. Figure 4. TGA curves of the precursors (pectin and 10KPEGMA) and copolymer P-10K. Figure 4. TGA curves of the precursors (pectin and 10KPEGMA) and copolymer P-10K.
3.3. Critical Gelation Concentration Determination 3.3. Critical Gelation Concentration Determination 3.3. Critical Gelation Concentration Determination Aqueous solutions of α-CD were added to P-10K solutions and the mixtures became gradually
Aqueous solutions ofturned α-CD were added to solutions and mixtures became gradually opaque. The mixtures white and formed gels after a timeand period. The effects of thegradually polymer Aqueous solutions of α-CD were added to P-10K P-10K solutions thethe mixtures became and α-CD concentrations onwhite gelling behavior were studied mixing a range of polymer and opaque. The mixtures turned gels afteraby atime time period. effects of theα-CD polymer opaque. The mixtures turned whiteand andformed formed gels after period. TheThe effects of the polymer compositions (1%–10% w/v). Hydrogel could be formed at a low polymer concentration of 1% (w/v) and α-CD concentrations on gelling behavior were studied by mixing a range of polymer and α-CD and α-CD concentrations on gelling behavior were studied by mixing a range of polymer and α-CD (Figure 5).(1%–10% The(1%–10% copolymer gelled at an optimum of 1% polymer and 5% (w/v) α-CD. compositions w/v). Hydrogel could be be ratio formed atata(w/v) concentration of 1% (w/v) compositions w/v). Hydrogel could formed alow lowpolymer polymer concentration ofYe 1%et(w/v) al. have reported that higher cyclodextrin concentrations increase the gel strength [24]. (Figure 5). copolymer The copolymer gelled at an optimum ratioofof1% 1%(w/v) (w/v) polymer polymer and α-CD. Ye Ye et et al. (Figure 5). The gelled at an optimum ratio and5% 5%(w/v) (w/v) α-CD. al. have reported that higher cyclodextrin concentrations increase the gel strength [24]. have reported that higher cyclodextrin concentrations increase the gel strength [24]. 10
Concentration of α-CD Concentration of α-CD (%) (%)
9 10
Gel
89
Gel
78 67 56 45 34
Liquid
23
Liquid
12 01 0
0
1
2
0
1
2 Concentration 3 4 5 of Polymer 6 7 (%) 8
3
4
5
6
7
8
9
10
9
10
Concentration of Polymer (%)
Figure 5. Sol-gel transition graph for different compositions of P-10K/α-CD.
Figure 5. Sol-gel transition compositions P-10K/α-CD. Figure 5. Sol-gel transitiongraph graphfor for different different compositions ofof P-10K/α-CD.
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3.4. Rheology of Pectin-PEGMA/α-CD Hydrogel
3.4. Rheology Pectin-PEGMA/α-CD Hydrogel The rheologyofof hydrogels prepared with 10% P-10K and 10% α-CD was investigated. Amplitude sweeps to measure shear strain were in the range of 0.01%–100% at temperatures of 25 ◦ C (room The rheology of hydrogels prepared with 10% P-10K and 10% α-CD was investigated. 3.4. Rheology of Pectin-PEGMA/α-CD Hydrogel Amplitude sweeps measure shear strain were the range proved of 0.01%–100% at temperatures of 25true °C gels temperature) and 37 ◦ Cto(body temperature). The in hydrogels to be highly structured, The rheology of hydrogels prepared with 10% P-10K and proved 10% α-CD was investigated. (room temperature) and 37 °C (body temperature). The hydrogels to be highly structured, with storage moduli (G’) greater then loss moduli (G”) at low shear strain (Figure 6). As the shear Amplitude sweeps to measure shear strainthen wereloss in the range(G”) of 0.01%–100% at temperatures 25the °C true gels with moduli (G’) greater moduli lowAs shear (Figure 6).ofAs strain(room increased, G’storage began to 37 decrease at temperature). a rate faster than that ofatG”. the strain oscillation strain increased temperature) and °C (body hydrogels structured, shear strain increased, G’ began to decrease at a rateThe faster than thatproved of G”. to Asbe thehighly oscillation strain fromtrue 0.01% 100%, the moduli hydrogels greater changed from gel (G’ > G”) toshear a liquid (G’ < G”). The critical gelsto with then loss a moduli at (G’ low (Figure As The the increased fromstorage 0.01% to 100%,(G’) the hydrogels changed from(G”) a gel > G”) tostrain a liquid (G’ G”) tohad a liquid < G”). shearing. The strain, G’ from dropped G”, the indicating that the gelfrom network been (G’ disrupted by critical strain of the hydrogel was around 7%–11% for P-10K. At a shear strain greater than the critical The linear viscoelastic region (LVR) of the hydrogels was 0.01% to 1% strain [25]. shearing. The linear viscoelastic region (LVR) of the hydrogels was 0.01% to 1% strain [25]. strain, G’ dropped below G”, indicating that the gel network structures had been disrupted by G"strain [25]. shearing. The linear viscoelastic region (LVR) of the hydrogels was 0.01%G' to 1% 25 °C 37 °C G' 25 °C 37 °C
105 5 4
G', G"G', (Pa) G" (Pa)
10 10
G"
1043 10 1032 10 1021 10 1010 10 10-2
10-1
0
10
10-2
10-1
100
101
102
Oscillation strain (%) 100 101
102
Figure 6. Amplitude sweeps performed from 0.01% to 100% of oscillation strain at 25 and 37 °C on strain Figure 6. Amplitude sweeps performedOscillation from 0.01% to (%) 100% of oscillation strain at 25 and 37 ◦ C on hydrogels prepared with 10% P-10K and 10% α-CD. hydrogels withsweeps 10% P-10K and 10% Figureprepared 6. Amplitude performed fromα-CD. 0.01% to 100% of oscillation strain at 25 and 37 °C on hydrogels prepared with 10% P-10K and 10% α-CD. Frequency sweeps were performed on the hydrogels from 0.01–50 Hz at 0.05% strain at 25 and
37 °C. G’ were higherwere than performed G” and bothon thethe moduli were dependent on frequency at both 25 and Frequency sweeps hydrogels from 0.01–50 Hz at 0.05% strain at 37 25 and
Frequency sweeps were performed on the hydrogels from 0.01–50 Hz atforces 0.05%orstrain at 25 and ◦ ◦ C.°CG’ (Figure 7). Frequency sweeps provide on the effect of colloidal interaction were higher than G” and both theinformation moduli were dependent on frequency at the both 25 and 37 C
37 37 °C. G’particles were higher than G” and both the moduli were dependent oninteraction frequencybetween at both 25 and 37 among [26]. As frequency increased, there on appeared to beofno particles, (Figure 7). Frequency sweeps provide information the effect colloidal forces or interaction the interaction °C (Figure 7). Frequency sweeps provide information on the effect of colloidal forces or the presumably because of sufficient separation to eliminate interactions and/or collisions. among particles [26]. As frequency increased, there appeared to be no interaction between particles, among particles [26]. As frequency increased, there appeared to be no interaction between particles, presumably because of sufficient separation interactionsand/or and/or presumably because of sufficient separationto toeliminate eliminate interactions G' collisions. G"collisions. 25 °C 37 °C G'
105 10 10
G', G"G', (Pa) G" (Pa)
G"
25 °C 37 °C
5 4
1043 10 1032 10 1021 10 1010 10 10-2
10-1
100
101
102
10-1
Frequency (Hz) 100
101
102
0
10
10-2
Figure 7. Frequency sweeps performed from 0.01 to(Hz) 50 Hz of oscillation strain at 25 and 37 °C on Frequency hydrogels prepared with 10% P-10K and 10% α-CD. Figure 7. Frequency sweeps performed from 0.01 to 50 Hz of oscillation strain at 25 and 37 °C on◦ Figure 7. Frequency sweeps performed from 0.01 to 50 Hz of oscillation strain at 25 and 37 C on hydrogels prepared with 10% P-10K and 10% α-CD.
hydrogels prepared with 10% P-10K and 10% α-CD.
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3.5. Thixotropic Properties of Pectin-PEGMA/α-CD Hydrogels
Instantaneously varying strain at 0.05% and 25% in amplitude sweeps for three cycles indicated 3.5. Thixotropic Properties of Pectin-PEGMA/α-CD Hydrogels that P-10K/α-CD hydrogels recovered their original gel structure (Figure 8) [27]. G’ was7 ofhigher than Polymers 2016, 8, 404 12 G” during the first 5 min of 0.05% strain and the gel was immediately sheared into a liquid where G’ Instantaneously varying strain at 0.05% and 25% in amplitude sweeps for three cycles indicated 3.5. Thixotropic Properties of Pectin-PEGMA/α-CD Hydrogels < G” during the 2.5 min of 25% strain. The liquid then reverted back to gel (G’ > G”) when the strain that P-10K/α-CD hydrogels recovered their original gel structure (Figure 8) [27]. G’ was higher than was reduced to 0.05%. the hydrogel some recovery time cycles to into revert back towhere the at 0.05% 25% amplitude sweeps forsheared three indicated G” during theInstantaneously first 5 minHowever, ofvarying 0.05%strain strain and and therequired gelinwas immediately a liquid that form. P-10K/α-CD hydrogelsnetwork recovered structure their original gel structure (Figure 8) [27]. G’shearing, was higherand thanrequired original gel The internal could be broken down by G’ < G” during the 2.5 min of 25% strain. The liquid then reverted back to gel (G’ > G”) when the G” during the first 5 min of 0.05% strain and the gel was immediately sheared into a liquid where G’ time was to rebuild, as shown by the coincides of G’ and G” at each 0.05% strain point after beingback sheared strain reduced 0.05%. theThe hydrogel required time to the revert to the < G” duringto the 2.5 minHowever, of 25% strain. liquid then reverted some back torecovery gel (G’ > G”) when strain at 25% strain. This shear–recovery phenomenon was repeatable for all the hydrogels at a minimum was reduced to internal 0.05%. However, the structure hydrogel required recovery time to back toand the required original gel form. The network could some be broken down byrevert shearing, of three cycles, proving thixotropy of P-10K/α-CD hydrogels. originalas gelshown form. the The network structure be each broken0.05% down strain by shearing, required time to rebuild, by internal the coincides of G’ andcould G” at pointand after being sheared time to rebuild, as shown by the coincides of G’ and G” at each 0.05% strain point after being sheared at 25% strain. This shear–recovery phenomenon was repeatable for all the hydrogels at a minimum of at 25% strain. This shear–recovery phenomenon was repeatable for all the hydrogels minimum G'at a G" three cycles, proving thixotropy of P-10K/α-CD hydrogels. of three cycles,the proving the thixotropy of P-10K/α-CD hydrogels. 25 °C 105 37 °C G'
10
104
G"
25 °C 37 °C
5
10
G', G" (Pa)
G', G" (Pa)
104 3
102
103 102
101
101
100
100
0
0
2
2
4
4
6
6
8
8
10 12 14 16 18 20 22 24
10 12 14 16 18 20 22 24 Time (min)
Time (min) Figure 8. Amplitude sweeps at 0.05% and 25% strains performed instantaneously for three cycles at
Figure 8. Amplitude sweeps at 0.05% and 25% strains performed instantaneously for three cycles at and 37 °C onsweeps hydrogels with25% 10% P-10K and 10% α-CD. instantaneously for three cycles at Figure 8.25Amplitude atprepared 0.05% and strains performed 25 and 37 ◦ C on hydrogels prepared with 10% P-10K and 10% α-CD. 25 and 37 °C on hydrogels prepared with 10% P-10K and 10% α-CD. 3.6. The Effect of Temperature on Pectin-PEGMA/α-CD Hydrogels
3.6. on Temperature sweeps were performed to probe Hydrogels the temperature responsiveness of P-10K/α-CD 3.6.The TheEffect Effectof ofTemperature Temperature onPectin-PEGMA/α-CD Pectin-PEGMA/α-CD Hydrogels
hydrogels (Figure 9) and demonstrated that these gels were not affected by temperature from 10 to
Temperature sweeps performed to the temperature responsiveness of P-10K/α-CD P-10K/α-CD Temperature sweeps wereG” performed toprobe probe thealmost temperature responsiveness of 40 °C. G’ was higherwere than and the moduli remained constant over this range. hydrogels gels were were not not affected affectedby bytemperature temperaturefrom from1010toto hydrogels(Figure (Figure9)9)and anddemonstrated demonstrated that these gels G' G" 4040◦ C. almost constant constantover overthis thisrange. range. °C.G’G’was washigher higherthan thanG” G”and and the the moduli moduli remained almost 105
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Figure9.9.Temperature Temperaturesweep sweepperformed performed from from 10 10 to to 40 40 °C ◦ C on Figure on hydrogel hydrogelprepared preparedwith with10% 10%P-10K P-10Kand and 10% α-CD. 10% α-CD.
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4. Discussion 4. Discussion Pectin-PEGMA Pectin-PEGMA copolymer copolymer was was successfully successfully synthesized synthesized through through cerium-initiated cerium-initiated radical radical polymerization, as evidenced by FTIR spectroscopy (Figure 3) and TGA (Figure The latter, latter, in polymerization, as evidenced by FTIR spectroscopy (Figure 3) and TGA (Figure 4). 4). The in particular, was diagnostic, indicating the presence of two components in P-10K and a shift in the particular, was diagnostic, indicating the presence of two components in P-10K and a shift in the degradation degradation temperature temperature of of the the copolymer copolymer relative relative to to its its component component precursors. precursors. Based Based on on the the weight weight change determined from these TGA curves (Table 1), it can be concluded there was 17% pectin in P-10K change determined from these TGA curves (Table 1), it can be concluded there was 17% pectin in P(Table 1). The FTIR spectra of this block copolymer supported the presence of pectin as a minority 10K (Table 1). The FTIR spectra of this block copolymer supported the presence of pectin as a minority component component (Figure (Figure 3). 3). Pectin-PEGMA Pectin-PEGMA copolymer copolymer was was able able to to form form gels gels with with α-CD α-CD (Figure (Figure 5). 5). The The α-CD α-CD threaded threaded onto onto PEG tendrils to form stacked inclusion complexes (Figure 10) [28,29] that interact with each other PEG tendrils to form stacked inclusion complexes (Figure 10) [28,29] that interact with each other to to aggregate hydrogen bonding These polypseudorotaxanes can interor intra-crosslink aggregate viavia hydrogen bonding [30].[30]. These polypseudorotaxanes can interor intra-crosslink with with each other while some chains of stacked inclusion complexes may remain separated (Figure each other while some chains of stacked inclusion complexes may remain separated (Figure 11).11). A A control experimentinvolving involvingmPEGMA mPEGMAalone aloneturned turnedopaque opaqueand andeventually eventually white white when when α-CD α-CD was control experiment was added, added, but but no no gel gel was was formed formed (Table (Table 2). 2). Inclusion Inclusion complexes complexes still still formed formed between between α-CD α-CD and and PEG PEG chains. However, the columns of threaded PEG chains remained free with no gelation [31]. P-10K chains. However, the columns of threaded PEG chains remained free with no gelation [31]. P-10K required of of 10% α-CD into 10% 10KPEGMA andand 10%10% P-10K required 5% 5%α-CD α-CDtotogel gel(Figure (Figure5).5).Upon Uponaddition addition 10% α-CD into 10% 10KPEGMA Psolutions, respectively, the co-polymer sample gelled, but not mPEGMA (Figure 12). 10K solutions, respectively, the co-polymer sample gelled, but not mPEGMA (Figure 12). The hydrogel to to shear shear strain strain and and its its dependence dependence on on frequency frequency The response response of of pectin-PEGMA/α-CD pectin-PEGMA/α-CD hydrogel demonstrated shear-thinning. The higher the strain percentage was, the more liquid-like the hydrogel demonstrated shear-thinning. The higher the strain percentage was, the more liquid-like the hydrogel became. The time time oscillation oscillation test test further further demonstrated demonstrated that that the the hydrogel hydrogel was was thixotropic. thixotropic. Thixotropic Thixotropic became. The materials provide a gel consistency when at rest and flow when shear is introduced (Figure 13). 13). materials provide a gel consistency when at rest and flow when shear is introduced (Figure Pectin-PEGMA/α-CD hydrogel was sheared beyond critical strain, but reverted back to gel on resting. Pectin-PEGMA/α-CD hydrogel was sheared beyond critical strain, but reverted back to gel on resting. Most with the the network Most PEG-grafted PEG-grafted polymers polymers are are temperature-sensitive, temperature-sensitive, with network structure structure disrupted disrupted by by an an increase in temperature [15,19]. High temperature may disrupt the non-covalent interactions increase in temperature [15,19]. High temperature may disrupt the non-covalent interactions in in supramolecular to to de-thread from PEGPEG chains [15]. [15]. The physical cross-linked supramolecular hydrogels, hydrogels,causing causingα-CD α-CD de-thread from chains The physical crossnetwork will then collapse. This effect notwas observed for pectin-PEGMA/α-CD hydrogel which linked network will then collapse. Thiswas effect not observed for pectin-PEGMA/α-CD hydrogel ◦ C. We hypothesize that pectin may confer thermal stability maintained its gel consistency from 10 to 40 which maintained its gel consistency from 10 to 40 °C. We hypothesize that pectin may confer thermal to the pectin-PEGMA/α-CD hydrogels. In support this proposition, it has been reported heat stability to the pectin-PEGMA/α-CD hydrogels. In of support of this proposition, it has been that reported treatment of milk does not affect the ability of pectin to stabilize particles such as casein and denatured that heat treatment of milk does not affect the ability of pectin to stabilize particles such as casein and whey complex [32]. denatured whey complex [32].
Figure 10. Threading α-CD onto PEG chains chains to to form form columns columns of of stacked stacked inclusion inclusion complexes. complexes. Figure 10. Threading of of α-CD onto PEG
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Figure 11.11. Polypseudorotaxanes interor or intra-crosslink with each other viavia hydrogen bonding. Figure Polypseudorotaxanes interintra-crosslink with each other hydrogen bonding. Figure Polypseudorotaxanes interintra-crosslink with each other hydrogen bonding. Figure 11.11. Polypseudorotaxanes interor or intra-crosslink with each other viavia hydrogen bonding. Table 2. Ten percent 10KPEGMA 10KPEGMA and and 10% 10% P-10K P-10K solutions solutions with with 10% 10% α-CD. α-CD. Table 2. Ten percent Table 2. Ten percent 10KPEGMA and 10% P-10K solutions with 10% α-CD. Table 2. Ten percent 10KPEGMA and 10% P-10K solutions with 10% α-CD. Sample Gel Sample Gel Gel 10KPEGMA Sample Gel Sample P-10K 10KPEGMA 10KPEGMA 10KPEGMA P-10KP-10K P-10K X
Figure 12. Pectin-PEGMA solution turned white after the addition of α-CD: (a) original 10% P-10K solution; (b) 10% P-10K solution after the addition of the α-CD (10%). Figure 12. Pectin-PEGMA solution turned white after addition α-CD: original 10% P-10K Figure 12.and Pectin-PEGMA solution turned white after the addition of of α-CD: (a)(a) original 10% P-10K Figure 12. Pectin-PEGMA solution turned white after the addition of α-CD: (a) original 10% P-10K solution; and (b) 10% P-10K solution after the addition of α-CD (10%). solution; and (b) 10% P-10K solution after the addition of α-CD (10%). solution; and (b) 10% P-10K solution after the addition of α-CD (10%).
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Figure hydrogels. Figure 13. 13. Thixotropic Thixotropic behavior behavior of of pectin-PEGMA/α-CD pectin-PEGMA/α-CD hydrogels.
In conclusion, (P-10K) copolymer was successfully synthesized using ceriumIn conclusion,pectin-PEGMA pectin-PEGMA (P-10K) copolymer was successfully synthesized using initiated radical polymerization in water. This process is a safer, greener, eco-friendlier way to graft cerium-initiated radical polymerization in water. This process is a safer, greener, eco-friendlier way polymers. α-CD wasα-CD incorporated into pectin-PEGMA copolymercopolymer and supramolecular gels were to graft polymers. was incorporated into pectin-PEGMA and supramolecular formed. copolymer gelled at low polymer (1%) with (1%) 5% ofwith α-CD. total gels wereThe formed. The copolymer gelled at lowconcentration polymer concentration 5% The of α-CD. concentration of polymer could be lowered to achieve a desired consistency of gel. These The total concentration of polymer could be lowered to achieve a desired consistency of gel. These supramolecular hydrogels were thixotropic, thixotropic, i.e., i.e., the the gel gel could could be be sheared supramolecular hydrogels were sheared to to liquid liquid and and reverted reverted back back to gel at rest. Industrially, a thixotropic material is easier to process or transfer without disrupting to gel at rest. Industrially, a thixotropic material is easier to process or transfer without disrupting the the consistency. Interestingly, pectin-PEGMA/α-CD hydrogels not affected by temperature consistency. Interestingly, pectin-PEGMA/α-CD hydrogels werewere not affected by temperature from ◦ from 10 to 40 °C, unlike the hydrogels of other PEG-grafted polymers [15,19,33,34]. This 10 to 40 C, unlike the hydrogels of other PEG-grafted polymers [15,19,33,34]. This supramolecular supramolecular hydrogel has potential to be developed for cosmetic, body and hair care products, or hydrogel has potential to be developed for cosmetic, body and hair care products, or even as an even as pharmaceutical an injectable pharmaceutical [35,36]. evaluating We are currently evaluating and the injectable incipient [35,36].incipient We are currently the biocompatibility biocompatibility and biodegradability of pectin-PEGMA and exploring the response of this material biodegradability of pectin-PEGMA and exploring the response of this material to other external stimuli. to other external stimuli. Supplementary Materials: The following are available online at www.mdpi.com/2073-4360/8/11/404/s1. Supplementary Materials: The following are available online at www.mdpi.com/2073-4360/8/11/404/s1. Figure Figure S1: 500 MHz 1 H NMR spectra of the precursors (pectin and 10KPEGMA) and of copolymer P-10K. S1: 500 MHz 1H NMR spectra of the precursors (pectin and 10KPEGMA) and of copolymer P-10K. Acknowledgments: Siew Yin Chan gratefully acknowledges the funding and support from Monash University Acknowledgments: Siew YinofChan gratefully acknowledges the funding and support from Monash Malaysia and the Institute Materials Research and Engineering, A*STAR. The authors thankUniversity Benjamin Qi Yu Chan and Cally Owh for their assistance with illustrations. Malaysia and the Institute of Materials Research and Engineering, A*STAR. The authors thank Benjamin Qi Yu Chan and Cally Owh forXian theirJun assistance withSim illustrations. Loh, Wee Choo and David James Young conceived and designed the Author Contributions: experiments. Siew Yin Chan and Xian Jun Loh designed the polymers. Siew Yin Chan synthesized and Author Contributions: Xian Jun Loh, Wee Sim Choo and David James Young conceived and designed the characterized the polymers. Siew Yin Chan, Wee Sim Choo, David James Young and Xian Jun Loh co-wrote the experiments. Siewdiscussed Yin Chantheand Xianand Jun Loh designed polymers. Siew Yin Chan synthesized and paper. All authors results commented on thethe manuscript. characterized the polymers. Siew Yin Chan, Wee Sim Choo, David James Young and Xian Jun Loh co-wrote the Conflicts of Interest: The authors declare no conflict of interest. paper. All authors discussed the results and commented on the manuscript.
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