Synthesis and characterization of biodegradable copolymer derived from dextrin and poly(vinyl acetate) via atom transfer radical polymerization

Abstract

This article reports the development of a dextrin-based amphiphilic biodegradable graft copolymer (Dxt-g-pVAc) via atom transfer radical polymerization (ATRP). The copolymer was synthesized by a “grafting from” approach using 2-bromopropionyl bromide as a bromo compound, vinyl acetate as a monomer and CuBr/bpy as an activator. The monomer concentration, temperature and time were varied to obtain the copolymer (Dxt-g-pVAc) with a relatively high molecular weight (M_n) and low polydispersity index (PDI). The synthesized copolymer was well characterized using FTIR and ¹H NMR spectral analyses, GPC, TGA, AFM, FESEM and EDAX analyses. The degree of substitution (DS) of dextrin was determined using ¹H NMR spectroscopy. A GPC kinetics study confirmed the livingness of the ATRP of vinyl acetate on dextrin. Scanning electron microscopy (SEM) analysis showed that the copolymer has a microporous morphology, whereas an atomic force microscopy (AFM) study indicated that the roughness of the copolymer decreased after the copolymerization of poly(vinyl acetate). The gel characteristics of the copolymer were investigated using rheological parameters. A biodegradation study using hen egg lysozyme confirmed the biodegradability of the copolymer.

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Introduction

Recently, the biopolymer dextrin has received significant interest for the development of functional materials with desired properties because of its chemical structure, solubility in aqueous media, low cost, commercial availability, non-cytotoxicity and biodegradable nature.¹ Dextrin is extensively used in various applications such as foods, textiles, and cosmetics.^1,2 To design macromolecular devices with essential features, it is imperative to modify dextrin with various functional groups, which may provide precise interfacial characteristics.¹ The modification of dextrin by grafting or crosslinking provides significant approaches that combine the benefits of using natural polysaccharides and synthetic polymers in different potential applications, including protein delivery,^3,4 MRI agents,⁵ superabsorbent materials,⁶ crosslinking agents,⁷ and drug delivery.^8–12 Although there are a few interesting reports in the literature on modified dextrin-based crosslinked hydrogels,^2,4,11–14 nanogels,^3,10 composites,^6,15 and conjugates,^16,17 which were developed by different techniques, such as enzymatic methods and conventional radical polymerization, control of the architecture using these methods was inadequate.¹⁸ Moreover, conventional free-radical polymerization is not controlled and thus causes an asymmetrical distribution of the grafted chain length and molecular weight, which directly influence the practical applications of the developed copolymers.¹⁹

Recently, atom transfer radical polymerization (ATRP) has acquired much attention for the synthesis of graft copolymers.¹⁸ This method involves a cyclic transition metal-catalysed reversible oxidation–reduction reaction.¹⁸ In this reaction, the metal appears in different oxidation states to attain a reversible dynamic equilibrium between propagating radicals and dormant species so that the polymerization reaction would be controlled.¹⁸ ATRP has several advantages such as mild conditions, simple operation, and the involvement of a wide range of monomers.²⁰ This method has been recognised to be useful for the development of functional polymeric networks with precisely controlled molecular weight, narrow polydispersity, definite architecture (combs, stars, rings, brushes, regular networks) and composition (graft, block, alternating, gradient copolymers).^18,19,21 On the other hand, graft copolymers are a network of main chain polymers with one or more side chains.^22,23 Grafting of a unique polymer with effective features onto the parent polymer can confer attractive surface properties such as wettability, non-specific adsorption, adhesion, responsiveness to stimuli and biocompatibility.²⁴ There are three synthetic methods for the development of graft copolymers via ATRP:^22,24,25 (i) “grafting through”, that requires a macromonomer for polymerization; (ii) “grafting from”, which involves the utilization of a macroinitiator for the polymerization of the monomer; and (iii) “grafting onto”, wherein properly functionalized polymeric chains are attached with a multifunctional backbone. Among the abovementioned methods, the “grafting from” method is a very effective route for obtaining a high grafting density and well-controlled polymer network on different types of surfaces.^24,25

In this article, we successfully developed a dextrin and vinyl acetate-based graft copolymer (Dxt-g-pVAc) via a “grafting from” approach. In the first step, a macroinitiator (Dxt-Br) was prepared using 2-bromopropionyl bromide and pyridine. Then, grafting of vinyl acetate on the macroinitiator occurred in the presence of CuBr/bpy activators. The reaction parameters were varied to obtain a graft copolymer with relatively higher molecular weight and lower PDI. Herein, we report for the first time on the development of a biodegradable copolymer derived from dextrin and poly(vinyl acetate) via ATRP.

Experimental section

Materials

Dextrin (source: potato starch) was purchased from Fluka, Switzerland. 2,2′-Bipyridine (bpy) was obtained from Loba Chemie, India. Pyridine, CuBr, dimethylsulfoxide and DCM were procured from Merck, India. 2-Bromopropionyl bromide (98% pure) and vinyl acetate were supplied by Acros Organics, USA. For all experimental study, double-distilled water was used.

Synthesis of dextrin macroinitiator (Dxt-Br)

At first, the required amount of dextrin was dissolved in a mixture of pyridine (Py) and DMSO (Table 1) at room temperature. Subsequently, the requisite amount of 2-bromopropionyl bromide (2-BPB) was added dropwise into the reaction mixture in an inert (N₂) atmosphere and ice-cold conditions under continuous stirring. The reaction was continued at room temperature for different time intervals (Table 1). The reaction mixture was poured into an excess amount of DCM for precipitation. The precipitate was washed thoroughly with DCM, filtered and dried under vacuum at 50 °C for 96 h. The reaction pathway and structure of the Dxt-Br macroinitiator are depicted in Scheme 1.

Table 1 Synthetic parameters of the Dxt-Br macroinitiator

10 mmol dextrin (Dxt) was taken in 15 mL DMSO
Materials	2-BPB (mmol)	Py (mmol)	Time (h)	% conversion	Mn (× 10^4 g mol^−1)	PDI	DS (%)
Dextrin	—	—	—	—	0.57	1.31	—
Dxt-Br 1	10	10	12	74.5	1.55	1.12	12.8
Dxt-Br 2	12	10	12	80.2	1.86	1.01	14.0
Dxt-Br 3	20	10	12	83.6	2.06	1.79	15.9
Dxt-Br 4	12	15	12	85.7	2.08	1.04	16.1
Dxt-Br 5	12	20	12	88.9	2.12	1.36	16.8

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Scheme 1 Schematic representation of the synthesis of Dxt-Br macroinitiator and Dxt-g-pVAc copolymer.

Synthesis of Dxt-g-pVAc copolymer via ATRP

The prerequisite amount of Dxt-Br 2 (Table 2) was dissolved in DMSO solution in a dried three-necked round-bottom flask at 40 °C on an oil bath fitted with a magnetic stirrer for 2 h. Then, N₂ gas was purged for 15 min. Subsequently, 2,2′-bipyridine, CuBr and vinyl acetate (Table 2) were added to the reaction medium separately. Furthermore, the temperature was increased to 60–70 °C and the mixture was stirred for 6–24 h (Table 2). The reaction was terminated on exposure to air. Then, the resulting mixture was precipitated in DCM and the precipitate filtered and dried at 50 °C under vacuum for 72 h (Table 2). The structure of the copolymer and mechanism of the reaction are explained in Scheme 1.

Table 2 Experimental data for the synthesis of Dxt-g-pVAc via ATRP

Copolymer	Dxt-Br 2 : VAc : CuBr : bpy (mmol)	DMSO (mL)	Temp. (°C)	Time (h)	Mn (× 10^4 g mol^−1)	PDI	Conversion (%)	Graft ratio (%)
Dxt-g-pVAc 1	0.1 : 100 : 0.1 : 0.2	20	60	6	2.57	1.23	26.21	245
Dxt-g-pVAc 2	0.1 : 100 : 0.1 : 0.2	20	60	8	2.94	1.12	27.72	278
Dxt-g-pVAc 3	0.1 : 100 : 0.1 : 0.2	20	60	12	3.89	1.14	31.13	330
Dxt-g-pVAc 4	0.1 : 100 : 0.1 : 0.2	20	60	24	6.02	1.16	42.23	550
Dxt-g-pVAc 5	0.1 : 100 : 0.1 : 0.2	20	70	8	8.17	1.11	50.57	671
Dxt-g-pVAc 6	0.1 : 150 : 0.1 : 0.2	20	70	6	8.68	1.13	53.89	760
Dxt-g-pVAc 7	0.1 : 150 : 0.1 : 0.2	20	70	8	8.95	1.13	55.22	820
Dxt-g-pVAc 8	0.1 : 150 : 0.1 : 0.2	20	70	12	10.83	1.15	58.35	953
Dxt-g-pVAc 9	0.1 : 150 : 0.1 : 0.2	20	70	24	12.13	1.28	65.45	1064
Dxt-g-pVAc 10	0.1 : 250 : 0.1 : 0.2	20	70	8	25.93	1.47	73.56	1647

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The monomer conversion and grafting ratio were calculated using eqn (1) and (2), respectively by the equations as follows:

where W_Br (g), W_Gft (g) and W_mon (g) are the dry weights of Dxt-Br, graft copolymer and monomer, respectively.²⁶

Characterization

The developed graft copolymer was characterized using GPC analysis, FTIR and ¹H NMR spectroscopy, SEM, AFM and TGA analyses. The detailed experimental procedure and instruments used are explained in the ESI.†

Rheological characteristics

The rheological characteristics of Dxt-g-pVAc 5 copolymer were determined in the swollen state at pH 7 and a temperature of 37 ± 0.1 °C using a Bohlin Gemini-2 rheometer (Malvern, UK) to investigate the gel characteristics of the prepared copolymer. A frequency sweep measurement was performed in the range of 1–10 Hz with a constant stress of 1 Pa. The elastic modulus (G′), viscous modulus (G′′) and gel strength of the copolymer (Dxt-g-pVAc 5) were determined by an oscillatory sweep measurement with a fixed gap of 500 μm. The experiment was performed with a constant frequency of 1 Hz and in the shear stress range of 1–1000 Pa using parallel-plate geometry. The shear viscosity of Dxt-g-pVAc 5 was measured in the shear rate range of 0.1–100 s⁻¹.

Biodegradation study

An enzymatic degradation study of Dxt-g-pVAc was carried out using lysozyme hydrochloride solution as explained in the previous literature.^11–13 The detailed procedure is explained in the ESI.†

Results and discussion

Synthesis of dextrin-Br macroinitiator

A schematic of the synthesis step of the Dxt-Br macroinitiator is shown in Scheme 1. The macroinitiator was obtained by the esterification of hydroxyl groups of dextrin using 2-bromopropionyl bromide as an acyl bromide. In this reaction, pyridine acted as a base to abstract hydroxyl protons of dextrin. Furthermore, the incorporation of bromoester groups occurred via an S_N² reaction.

As a result of the exothermic nature of the reaction, the bromo compound was added in ice-cold conditions. The macroinitiator (i.e. Dxt-Br 2) with relatively higher molecular weight and lower PDI (Table 1) was used for the further synthesis of the graft copolymer. It has been observed that the molecular weight and percentage conversion increased with the Dxt-Br macroinitiator (Table 1, Fig. 2 and S1, ESI†), which is probably because of the increase in the ratio of 2BPB : Py, whereas the lower PDI may be due to the occurrence of chain scission, which resulted in the chains being more evenly distributed.

Synthesis of Dxt-g-pVAc copolymer

Scheme 1 represents the formation of the Dxt-g-pVAc copolymer via ATRP. The polymerization reaction was carried out in DMSO using CuBr/bpy as activators. This is a catalytic process mediated by redox-activated transition metal complexes (CuBr/bpy and CuBr₂/bpy).

To obtain a copolymer with a narrow PDI, we altered the monomer concentration, temperature and time (Table 2). The number average molecular weight (M_n) of the graft copolymers varied from 25 710 to 259 303 g mol⁻¹ (Table 2, Fig. 1b and c and S2, ESI†) with a narrow PDI, which suggests that the formation of the copolymer is “living” in nature.

Fig. 1 (a) Kinetics study and (b) and (c) molecular weight/PDI vs. percentage monomer conversion for Dxt-g-pVAc copolymers obtained via ATRP at 60 °C and 70 °C.

The effects of the monomer concentration (vinyl acetate) and monomer : initiator ratio on the molecular weight and PDI of the graft copolymers at different temperatures (60 °C and 70 °C) are shown in Table 2. It is obvious that with an increase in the vinyl acetate concentration from 100 mmol to 250 mmol, the percentage conversion (Table 2) as well as the molecular weight of the Dxt-g-pVAc increased. Moreover, the PDI values remained in a narrow range, which indicates that the grafting of vinyl acetate occurred via ATRP (Table 2/Fig. 1).

To confirm the livingness of the graft copolymerization, the reaction time was varied (Table 2) and kinetics studies were performed. From Fig. 1a, it is evident that the plots of ln([M]₀/[M]) vs. time and M_n vs. percentage conversion are linear, which reveals that the polymerization was first-order (where [M]₀ and [M] are the initial monomer concentration and monomer concentration at time t, respectively).

Significantly, the PDI values are in a narrow range, which implies that the grafting of vinyl acetate on dextrin is a controlled living radical polymerization. When the molar ratio of the reactants (Dxt-Br : VAc CuBr : bpy) was 0.1 : 100 : 0.1 : 0.2 (mmol) at 70 °C, the copolymer (Dxt-g-pVAc 5) was formed with a relatively high molecular weight (8.17 × 10⁴ g mol⁻¹) and lower PDI (1.11) (Table 2, Fig. 2).

Fig. 2 GPC plot of dwt/d(log M) vs. slice log M_w of dextrin, Dxt-Br 2 macroinitiator and Dxt-g-pVAc 5 copolymer.

Characterization of Dxt-g-pVAc copolymer

The FTIR spectrum of dextrin (Fig. 3a) exhibits five characteristic peaks at 3393, 2925, 1425, 1155 and 1025 cm⁻¹, which are assigned to O–H stretching, C–H stretching, C–H bending, C–O–C asymmetric and C–O–C symmetric stretching vibrations, respectively.

Fig. 3 FTIR spectra of (a) dextrin, (b) Dxt-Br 2, and (c) Dxt-g-pVAc 5 copolymer.

In the FTIR spectrum of Dxt-Br 2, the absorption peak at 1736 cm⁻¹ (Fig. 3b) is assigned to the C=O stretching frequency. The peak at 685 cm⁻¹ is assigned to the C–Br bond vibration. Moreover, the intensity of the O–H bond stretching of the dextrin moiety decreases, which indicates the esterification reaction between dextrin and the bromo compound. Thus, the appearance of the new peaks (for C=O and C–Br) and the reduction in the O–H bond vibration signify the successful incorporation of the bromo compound in the dextrin moiety.

In the FTIR spectrum of Dxt-g-pVAc copolymer (Fig. 3c), all the characteristic peaks of the macroinitiator (Dxt-Br 2) are present. However, the peak of the carbonyl group (C=O) is shifted from 1736 cm⁻¹ to 1745 cm⁻¹, which is because of the insertion of the C=O group of vinyl acetate. This suggests the grafting of poly(vinyl acetate) on the dextrin backbone.

From the ¹H NMR spectrum of dextrin (Fig. 4a, 400 MHz, DMSO-d₆, ppm), the peaks at δ = 3.323–3.595, 5.449 and 5.362 are attributed to H2–H6, anomeric protons (H1) and anomeric protons in α-1,6 linkages (<5% of the total for dextrin), respectively (Fig. 4a). The peaks at δ = 4.540 and 4.865–5.061 are assigned to –OH (2) and –OH (3, 4 or 6) protons, respectively.^3,27

Fig. 4 ¹H NMR spectra of (a) dextrin and (b) Dxt-Br 2 macroinitiator in DMSO-d₆.

In the ¹H NMR spectrum of the Dxt-Br 2 macroinitiator (Fig. 4b, 400 MHz, DMSO-d₆, ppm), the new peaks at δ = 5.758–5.813 (q) are attributed to H^a protons, whereas the peaks at δ = 1.861–1.880 (d) are due to –CH₃ protons (H^b). In general, primary hydroxyl protons [–OH (6)] are more acidic than secondary protons [–OH (2, 3, 4, 6)]. Moreover, from the ¹H NMR spectrum of Dxt-Br 2, it is obvious that the peak intensities of –OH (2) and –OH (3, 6) protons in dextrin decreased sharply. The decrease in peak intensities and the appearance of additional peaks confirmed that most of the substitution occurred on the –OH (2, 3, 6) positions of dextrin, further confirming the formation of the Dxt-Br macroinitiator.

Quantification of degree of substitution (DS). The degree of substitution (DS) was determined by performing integration of the signals of the methyl protons of the bromo compound and the protons of the polysaccharide unit (excluding the protons of hydroxyl groups, which were not measured by this method).²⁸ As each polysaccharide unit has seven protons (apart from the OH-protons) and each methyl group has three protons, thus the DS was determined using eqn (3) given as follows:where I_me and I_Polys are the values of the integration areas of the methyl protons and polysaccharide protons, respectively. It was observed that the DS of the macroinitiator varied from 12.8% to 16.8% (Fig. 4b, S3–S6† and Table 1).

In the ¹H NMR spectrum of Dxt-g-pVAc 5 (Fig. 5, 400 MHz, DMSO-d₆, ppm), there are peaks at δ = 1.190 (broad, 3H, i.e., H^d), 1.910 (broad, 3H, i.e., H^g), 2.279–2.295 (m, 2H, i.e., H^e), 2.621–2.633 (q, 1H, i.e., H^c), and 5.922 (m, 1H, i.e., H^f). Moreover, the shifting of the peaks for H^a protons (5.758–5.813) to H^c (2.621–2.633) and H^b protons (1.861–1.880) to H^d (1.190), along with the appearance of new peaks for H^e, H^f and H^g protons, confirmed the formation of the Dxt-g-pVAc copolymer via ATRP.

Fig. 5 ¹H NMR spectrum of Dxt-g-pVAc 5 copolymer in DMSO-d₆.

The surface morphologies of dextrin, the Dxt-Br 2 macroinitiator and the Dxt-g-pVAc 5 copolymer are shown in Fig. 6. Dextrin (Fig. 6a) has a fine granular morphology. After reaction with the bromo compound, the granular morphology of dextrin changed to macroporous (Fig. 6b), which suggested the formation of the macroinitiator. Moreover, on copolymerization with poly(vinyl acetate), the macroporous morphology of Dxt-Br changed to microporous. The decrease in porosity indicates the formation of the copolymer (Fig. 6c).

Fig. 6 SEM images of (a) dextrin, (b) Dxt-Br 2, and (b) Dxt-g-pVAc 5 copolymer (magnification ×800).

Fig. S7, ESI† presents EDX analyses of Dxt-Br 2 and the Dxt-g-pVAc 5 copolymer. The presence of Br along with C and O indicates good distribution of Br on the surface of the macroinitiator and graft copolymer. It further signifies the successful synthesis of the macroinitiator, which acts as an effective initiator for the grafting of vinyl acetate on the dextrin moiety.²⁹

From two-dimensional (Fig. 7a) and three-dimensional (Fig. 7c) AFM height images of the Dxt-Br 2 macroinitiator, it is apparent that the surface is rough with a root-mean-square (RMS) roughness value of 17.32 nm. However, after grafting, the surface roughness of Dxt-g-pVAc 5 decreased, with an RMS roughness value of 3.58 nm (Fig. 7b and d).

Fig. 7 Two-dimensional height sensor (a and b), 3-dimensional height sensor (c and d) and phase images (e and f) of Dxt-Br 2 (a, c and e) and Dxt-g-pVAc 5 copolymer (b, d and f) as cast film.

Moreover, in the phase images (Fig. 7f), the relatively bright spots are probably because of the presence of poly(vinyl acetate) in the graft copolymer, whereas the dark regions (Fig. 7e and f) may be due to the esterification of dextrin by 2-bromopropionyl bromide. The appearance of dark regions over the bright surface of dextrin suggests the presence of two distinct units, which also supports the grafting of poly(vinyl acetate) on the dextrin moiety.

Fig. 8 depicts TGA analyses of dextrin, Dxt-Br 2 and Dxt-g-pVAc 5. The TGA curve of dextrin (Fig. 8) shows two weight loss regions: (a) below 100 °C, which is due to the presence of moisture, and (b) the region at temperatures between 258 °C and 298 °C is due to the degradation of the dextrin backbone. In the TGA plot of Dxt-Br 2, the weight loss zone between 122 °C and 210 °C is assigned to the degradation of the bromo compound. Moreover, the TGA curve of Dxt-g-pVAc 5 exhibited three additional regions of weight loss (Fig. 8): (i) 112–220 °C, which is because of the breakage of macroinitiator units; (ii) 240–310 °C, which is due to the deacetylation of PVAc units and breakdown of polysaccharide moieties; and (iii) 320–370 °C, which is assigned to the degradation of aromatic hydrocarbons, i.e., polyenic structures produced during the degradation of PVAc.³⁰

Fig. 8 TGA plots of dextrin, Dxt-Br 2 and Dxt-g-pVAc 5.

Rheological study

Fig. 9 presents the rheological characteristics of the Dxt-g-pVAc 5 copolymer at pH 7.0. From the frequency sweep measurement (Fig. 9a), it was observed that the storage modulus (G′) is greater than the viscous modulus (G′′).

Fig. 9 Plots of (a) G′ and G′′ vs. frequency, (b) G′ and G′′ vs. shear stress, and (c) shear viscosity vs. shear rate using Dxt-g-pVAc 5 copolymer.

Moreover, the increases in both moduli with frequency signify the elastic nature of the Dxt-g-pVAc 5 copolymer. In addition, the strength of the copolymer was determined from a plot of G′ and G′′ vs. shear stress (Fig. 9b). Both G′ and G′′ decreased above a definite shear stress (i.e. the yield stress, σ)¹³ (here, σ = 236 Pa). This was because of the breakdown of the grafting network. Moreover, the decrease in shear viscosity with an increase in shear rate (Fig. 9c) suggests non-Newtonian shear thinning behavior of the Dxt-g-pVAc 5 copolymer.

Biodegradation study

Fig. 10 indicates the results of the degradation of the Dxt-g-pVAc 5 copolymer after 0, 3, 7 and 14 days using lysozyme. Hen egg white lysozyme has similar binding sites to those present in human lysozyme.¹³ The progressive weight loss (Fig. 10) implies the degradation of the copolymer in the presence of lysozyme. Lysozyme degrades a polysaccharide backbone by enzymatic hydrolysis of the glycosidic bonds.^12,13,31 However, after breakage of the polysaccharide backbone at pH 7.4, the ester linkage of the copolymer was hydrolysed, which was also responsible for further weight loss (Fig. 10).

Fig. 10 Progressive mass loss of Dxt-g-pVAc 5 in lysozyme/PBS. Results represented are mean ± SD, n = 3.

Conclusions

A novel biodegradable porous copolymer (Dxt-g-pVAc) was successfully synthesized using dextrin as a biopolymer, 2-bromopropionyl bromide as a bromo compound, and CuBr/bpy as catalysts via ATRP. The effects of monomer concentration, temperature and time were investigated. When the temperature of the reaction was 70 °C and the molar ratio of Dxt-Br 2 : vinyl acetate : CuBr : bpy (mmol) was 0.1 : 100 : 0.1 : 0.2, a graft copolymer (Dxt-g-pVAc 5) was formed with a relatively high molecular weight and lower PDI. Rheological parameters suggest that the developed copolymer exhibited gel characteristics in aqueous media. Finally, a kinetics study revealed that the polymerization was a controlled living radical polymerization.

Acknowledgements

The first author acknowledges the University Grant Commission, New Delhi, India (Reference No. 19-06/2011(i) EU-IV; Sr. No. 2061110303, dated Nov 30, 2011) for providing financial assistance under the Junior Research Fellowship Scheme. The corresponding author (S. P.) acknowledges the financial support from SERB, Department of Science & Technology, New Delhi, India in the form of a research grant (File No. EMR/2014/000471).

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Footnote

† Electronic supplementary information (ESI) available: Characterization techniques, ¹H NMR spectra of various grades of Dxt-Br macroinitiator, GPC and EDAX analyses result. See DOI: 10.1039/c5ra22762c

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