Bio-Medical Materials and Engineering 24 (2014) 695–701 DOI 10.3233/BME-130857 IOS Press

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Influence of sheath solvents on the quality of ethyl cellulose nanofibers in a coaxial electrospinning process Deng-Guang Yu*, Xiao-Yan Li, Wei Chian, Ying Li and Xia Wang* School of Materials Science & Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China

Abstract. The influence of different types of solvents as sheath fluids on the quality of electrospun ethyl cellulose (EC) nanofibers is investigated in this paper by a modified coaxial process. With 24 w/v % EC in ethanol as electrospinning core fluid and pure solvents including methanol, ethanol and N,N-dimethyl formamide (DMF) as sheath fluids, EC nanofibers were generated by the modified processes. Field emission scanning electron microscope observations demonstrate that the modified process is effective in improving the nanofibers’ quality in terms of nanofibers’ diameters, distributions and structural uniformity. The key of the modified coaxial process is the reasonable selection of the sheath solvents that is suitable for the drawing process of core EC fluid during the electrpospinning. The EC nanofibers’ diameters (D, nm) could be manipulated through the reasonable selection of the type of the sheath solvents based on their boiling point (T, °C) D = 841-3.71T (R= 0.9753). This paper provides useful methods for the implementation of the modified coaxial process controllably to obtain polymer nanofibers with high quality. Keywords: Coaxial electrospinning, sheath solvent, nanofibers, quality, ethyl cellulose

1. Introduction As an advanced nanotechnology technique, coaxial electrospinning has the capability, flexibility, and practicality for producing core/sheath nano-structures and micro-structures through a concentric spinneret that can accommodate two different liquids [1, 2]. It is regarded as one of the most significant breakthroughs in the electrospinning field, and has been applied broadly in controlling the secondary structures of nanofibers, encapsulating drugs and biological agents into polymer nanofibers, preparing nanofibers from materials that lack filament-forming properties, and enclosing functional liquids within an existing fiber matrix [3–7]. It is common sense that sheath fluids must have enough viscosity to overcome the interfacial tension caused by “viscous dragging” and “contact friction” between two solutions for a successful coaxial electrospinning process [3]. However, a modified coaxial electrospinning process has been recently reported [8–11] that is characterized by unspinnable sheath fluids such as pure solvents, mixed solvents, solutions with small-sized molecules, and dilute polymer solutions [12]. *

Corresponding author. E-mail: [email protected]; [email protected].

0959-2989/14/$27.50 © 2014 – IOS Press and the authors. All rights reserved

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In this study, a modified coaxial electrospinning process is developed to prepare ethyl cellulose (EC) nanofibers using different types of solvents as sheath fluids. EC is used as a model filament-forming polymer. It is a derivative of cellulose having a defined percentage of the hydroxyl groups in the repeating glucose units that are substituted with ethyl ether groups. It fulfills all requirements of the major pharmacopoeias (USP, EP, and JP) and food regulations, and is often selected as a drug carrier and polymer matrix to generate composite fibers and microparticles to achieve sustained-release profiles [13]. 2. Experimental 2.1. Materials The EC (6 mPa·s to 9 mPa·s) used in this study was obtained from Aladdin Chemistry Co., Ltd (Shanghai, China). Methylene blue, methanol, anhydrous ethanol and N, N-dimethyl formamide (DMF) were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). All other chemicals used were of analytical grade. 2.2. Modified coaxial electrospinning Core solutions were prepared by dissolving 24 g EC and 2 mg methylene blue in 100 mL ethanol. Three types of pure solvents, i.e., methanol, ethanol, and DMF, were trialed as sheath fluids for carrying out modified coaxial electrospinning to generate EC nanofibers. Two syringe pumps (KDS100 and KDS200, Cole-Parmer, IL, USA) and a high-voltage power supply (ZGF 60kV/2 mA, Shanghai Sute Corp., Shanghai, China) were used for coaxial electrospinning. A homemade concentric spinneret was used to conduct the coaxial electrospinning processes. The electrospinning process was recorded using a digital video recorder (PowerShot A490, Canon, Tokyo, Japan). After some pre-experiments, the applied voltage was fixed at 14 kV, and the nanofibers were collected on an aluminum foil at a distance of 20 cm. All other parameters are listed in Table 1. Table 1 Parameters of EC nanofibers and their preparation a

No. F1 F2 F3 F4 b

Electrospinning Diameter Morphology b (μm) Sheath fluid Core fluid None Line 860 ± 230 EC ethanol Methanol Line 670 ± 130 solution Ethanol Line 410 ± 110 DMF Mixed 300 ± 140 a The sheath-to-core flow rate ratio is fixed at 0.2/0.8 except for nanofibers F1

In this column, “Line” morphology refers to nanofibers having few beads or spindles on them; “Mixed” morphology refers to nanofibers having beads/spindles.

2.3. Characterization The surface morphologies of electrospun fibers were assessed using a JSM-5600LV field emission scanning electron microscope (FESEM, Japan Electron Optics Laboratory Co. Ltd.). Prior to examination, the samples were gold sputter-coated in an argon atmosphere to render them electrically conductive. Pictures were then taken at an excitation voltage of 10 kV. The average nanofiber

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diameter was determined from FESEM images, using Image J software (National Institutes of Health, USA) by measuring diameters of fibers at over 100 different locations. 3. Results and discussion 3.1. Coaxial electrospinning process A schematic diagram of the modified coaxial electrospinning process with a solvent as the sheath fluid is shown in Figure 1(a). The homemade concentric spinneret used to carry out the modified process is depicted in the inset of Figure 1(a). When single fluid electrospinning of the EC solutions was conducted with a sheath flow rate of zero, the spinneret clogged from time to time. The fast evaporation of ethanol on the surface of the fluid jet led to the formation of a highly viscous semi-solid substance, which clung to the nozzle of spinneret, thus retarding the electrospinning process. Manual remove of this semi-solid substance was required to keep the electrospinning process going. When conducting the modified coaxial electrospinning process to prepare the EC nanofibers, two syringe pumps were used to drive the sheath and core fluids independently. An alligator clip was used to connect the inner stainless steel capillary with the high voltage supply (Figure 1(b)). With ethanol as the sheath fluid, and with a sheath-to-core flow rate ratio of 0.25, a typical fluid jet trajectory was produced, in which a Taylor cone was followed by a straight fluid jet and a bending and whipping instability region (Figure 1(c)). The compounded Taylor cone is composed of two parts, with the sheath solvent clearly surrounding the core polymer solutions, indicated by the methylene blue in the inset of Figure 1(c).

Fig. 1. Modified coaxial electrospinning process and equipment: (a) Schematic diagram of the modified process, the inset is the homemade concentric spinneret; (b) a digital picture of the connection of the concentric spinneret with the power supply; (c) a typical coaxial electrospinning process with ethanol as the sheath fluid with a sheath-to-core flow rate ratio of 0.25 (at 12x magnification), the inset is a compound Taylor cone.

The coaxial electrospinning process can be carried out without any clogging and run smoothly, using all the EC solution in the syringe. Solvent evaporation and viscosity of the solution have strong impacts on clogging, as noted above. The high volatility of a solvent accelerates its evaporation, and increases the likelihood of clogging [14]. This is because the applied electric field cannot overcome

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the viscous drag force. If the solution viscosity is too high, it is possible that the applied electrical force may not be adequate to overcome the viscous drag force at the droplet-air interface, leading to clogging at the spinneret. When a sheath solvent is used to surround the core EC solution during electrospinning, it effectively prevents the fast evaporation of the ethanol from the surface of the core EC solutions, and retards the formation of any “skin” surface, resulting in smooth electrospinning of the EC solutions. 3.2. Morphology and size of nanofibers Nanofibers obtained from single fluid and modified coaxial electrospinning processes are shown in Figure 2, and the nanofibers’ diameter distributions are given in Figure 3. All the nanofibers had a linear morphology, except F4 nanofibers, which had the typical beads-on-a-string morphology (Figure 2(d)). F1 Nanofibers, obtained from the single fluid electrospinning, are shown in Figure 2(a), and they had an average diameter of 860 ± 230 nm (Figure 3(a)). Besides having a larger diameter, F1 nanofibers also have a wide distribution of diameters. Using methanol and ethanol as sheath fluids, the resultant F2 and F3 nanofibers were narrower (Figures 2(b), 2(c) and Figures 3(b), 3(c)), with diameters of 670 ± 130 nm and 410 ± 110 nm, respectively. Since both F2 and F3 nanofibers had diameters smaller than F1 nanofibers, this indicates that nanofibers from the modified coaxial process have better quality in terms of diameter size, distribution and structural uniformity. However, when DMF is used as a sheath fluid, the resulting EC nanofibers show the typical spindles-on-a-string morphology although the diameters are further diminished to 300 ± 140 nm (Figures 2(d) and 3(d)).

Fig. 2. FESEM images of EC nanofibers: (a) F1; (b) F2; (c) F3; (d) F4, the scale bar represents 5 μm

Solvent selection is a significant factor in determining both the electrospinnability of polymer solutions and the quality of the resultant nanofibers in traditional single fluid electrospinning. In the modified coaxial process, the physical properties of the sheath solvent (i.e. boiling point, conductivity and surface tension) have an impact on the process, thus influencing the quality of the resultant nanofibers. In the present study, all the three types of sheath solvents have poorer conductivity than the core solutions due to the presence of EC in the ethanol. The surface tension mainly has an impact on the initiation of the electrospinning process. Thus, the different boiling points are likely to be the

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main factor in the generation of EC nanofibers of differing morphology and size. This is reflected in the results showing that as solvent boiling point increases: methanol (65 °C) < ethanol (78 °C) < DMF (155 °C), the resultant nanofibers diameter decreases: methanol (670 ± 130 nm) > ethanol (410 ± 110 nm) > DMF (300 ± 140 nm). Provided that the boiling point of the gas (the single fluid electrospinning for preparation of F1 nanofibers was conducted in the open atmosphere) is the ambient temperature (21 °C), an inverse relationship between solvent boiling points and diameters of nanofiber can be described as D (nm) = 841-3.71T (°C), with a correlation coefficient of 0.9753 (Figure 2(e)), where D is the nanofibers’ diameter and T is the temperature of solvent boiling point. These results demonstrate that boiling points play a key role in controlling the diameter of nanofibers. The primary reason for including a sheath solvent in the process is to synthesize finer nanofibers by reducing solvent evaporation from the surface of the core electrospinning polymer solution. This enables the polymer jet to have a longer electrical drawing force in the fluid phase. Thus, the period spent by the sheath solvent in company with the core fluid during coaxial electrospinning could be a key factor for influencing the quality of resultant nanofibers. Both ethanol and methanol are volatile, they can surround the core EC solution in a reasonable time period and thus they can reduce the size of the EC nanofibers and make the nanofibers more homogeneous by improving the resistance during the electrospinning process to increase stability. However, since DMF has a high boiling point of 155 °C and is an aprotic solvent, a resulting 0.25 sheath-to-core flow rate ratio would make evaporation of the DMF sheath difficult in a suitable time. Hence, DMF would surround and remain with the core fluid as it enters the second or third bending instability regions and perhaps even as it enters the collector. Thus, although smaller nanofibers can be produced using DMF as a sheath solvent, the persistence of DMF negatively influences nanofiber quality.

Fig. 3. Nanofiber diameters’ distributions: (a) F1; (b) F2; (c) F3; (d) F4; and (e) the relationships between the EC nanofibers’ diameter and the sheath boiling point.

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3.3. Mechanisms When modified coaxial electrospinning is carried out, the sheath solvent exerts the following influences on the process: (1) facilitating the formation of a Taylor cone due to having lower surface tensions; (2) surrounding the straight thinning jet of the core electrospinning EC solutions, which retards the fast evaporation of the core solvent, while the sheath solvent itself outwardly evaporates to the open air (as indicated by “A” in Figure 4); and (3) following the core fluid to enter the instability region. The primary reason why the sheath solvent thins the nanofibers is the solvents’ retarding effect on evaporation from the surface of the core spinning polymer solutions, which in turn maintains the fluid state of the core jet so that it can be effectively subjected to electrical drawing for a longer period in the instability region. This is the most likely reason why the modified coaxial electrospinning process generates thinner EC nanofibers than single fluid electrospinning (as indicated by “B” in Figure 4). The single fluid electrospinning process is very sensitive to environmental changes, in particular when the spinnable liquid is prepared from volatile organic solvents such as ethanol. The modified process presented in this study provides a stable and robust core-sheath interface for the core EC solutions to be drawn into the electrical field, keeping them from the disturbances of any environmental changes. This modified coaxial process can produce EC nanofibers with more uniform diameter distributions. However, when a solvent with a high boiling point such as DMF is used and also has a relatively big sheath-to-core flow rate ratio, the surrounding solvent remains with the core fluid for a relatively longer time and breaks into separate segments along the core EC jets due to its lack of viscoelasticity. It is postulated that the divided sheath solvent might mix with the core fluid locally to form sections of the fluid jet having different local polymer concentrations, which in turn result in nanofibers with a beads-on-a-string structure, as shown in Figure 2(d).

Fig. 4. The proposed mechanisms of sheath solvent on the formation of EC nanofibers using modified coaxial electrospinning

4. Conclusions A modified coaxial electrospinning process, in which only pure organic solvents are used as sheath fluids, has been successfully developed to produce EC nanofibers. FESEM observations show that the modified coaxial electrospinning process is an effective method for preparing high quality EC nanofibers in terms of nanofibers’ diameter, distribution, and structural uniformity. The key to the

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modified coaxial process is the selection of the appropriate type of sheath solvent, which must match the drawing process of the core EC fluid during electrospinning. The EC nanofibers’ diameters (D, nm) can be manipulated by the selection of different types of the sheath solvents based on their boiling point (T, °C) as D = 815-3.45 T (R = 0.9657). The mechanism of the sheath solvent’s influence on the formation of EC nanofibers is discussed. This report provides a simple method for implementing a modified coaxial process to smooth electrospinning and obtain high quality polymer nanofibers. 5. Acknowledgements This work was supported by the Natural Science Foundation of Shanghai (No.13ZR1428900), the Key project of Shanghai Municipal Education Commission (No.13ZZ113), and the Innovation project of University of Shanghai for Science and Technology (No. 13XGM01).

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Influence of sheath solvents on the quality of ethyl cellulose nanofibers in a coaxial electrospinning process.

The influence of different types of solvents as sheath fluids on the quality of electrospun ethyl cellulose (EC) nanofibers is investigated in this pa...
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