Electrospinning of Cellulose Acetate Phthalate from Different Solvent

Jan 6, 2010 - Electrospinning of cellulose acetate phthalate (CAP) has been performed from an acetone-water mixture. 85/15 (v/v), 2-methoxyethanol, an...
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Ind. Eng. Chem. Res. 2010, 49, 1953–1957

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Electrospinning of Cellulose Acetate Phthalate from Different Solvent Systems Niculae Olaru* and Liliana Olaru “Petru Poni” Institute of Macromolecular Chemistry, Aleea Grigore Ghica-Voda 41A, Iasi 700487, Romania

Electrospinning of cellulose acetate phthalate (CAP) has been performed from an acetone-water mixture 85/15 (v/v), 2-methoxyethanol, and a 2-methoxyethanol-acetone-water mixture 50/42.5/7.5 (v/v/v). It has been observed that, at low polymer concentration (12.5%, w/v), a solution in an acetone-water mixture 85/15 (v/v) gave uniform fibers with diameters lower than 500 nm, whereas in 2-methoxyethanol fine particles that look like void hemispheres were obtained. The morphology of the electrospun CAP from this solvent gradually changed by increasing the polymer concentration and beaded fibers and fibers without beads have been produced from solutions of 25% (w/v) and 35% (w/v), respectively. Smooth filaments with no beads and diameters of about 600 nm could be obtained from a solution of CAP in the ternary system 2-methoxyethanol-acetone-water 50/42.5/7.5 (v/v/v) at a polymer concentration of 25% (w/v). The electrospinnability of CAP from 2-methoxyethanol-containing solvents was better than that from the acetone-water mixture 85/15 (v/v). Introduction Cellulose is a natural resource of great interest in polymer science because of its versatility and biodegradability. Either derivatized or not, cellulose found many uses in various technical and medical fields. A particular concern in recent decades is related to the possibility of producing cellulose and cellulose derivatives as powders and fibers with dimensions in the submicrometer range. The reason for this approach is based on recent findings regarding the new and interesting properties of nanostructured materials. The very high specific surface area and porosity of ultrafine fibers or powders make them suitable for a wide range of advanced applications in filtration, catalysis, sensors, tissue-engineering scaffolds, protective clothing, affinity membranes, controlled release, etc.1,2 Cellulose derivatives like cellulose acetate,3-8 ethyl cellulose,9-11 carboxymethyl cellulose sodium salt, hydroxypropyl methylcellulose, and methylcellulose12 and also underivatized cellulose11,13-15 have been electrospun from their solutions in adequate solvents and their possible applications especially in biomedicine and technology are reported. Cellulose acetate phthalate (CAP) is a mixed ester of cellulose commonly used as a pharmaceutical excipient for enteric coating of tablets and capsules. Recent literature revealed that when properly formulated, CAP also exhibits activity against the human immunodeficiency virus type I (HIV-I), several herpes viruses (herpes simplex viruses I and II), and also many nonviral sexually transmitted disease pathogens.16-21 Because of its water insolubility at pH < 5.5, micronized CAP formulations have been prepared and the interaction between micronized CAP and HIV-1 was investigated and compared with antiviral properties of other anti-HIV-1 microbicides.22 A microbicidal composite of CAP-hydroxypropyl cellulose has also been obtained as water-dispersible film by casting from organic solvent mixtures and its potential usefulness as a topical microbicide is reported.19 Electrospinning is an adequate procedure that has been intensively studied in the past decade2 for obtaining ultrafine polymer fibers that exhibit a very high surface-to-volume ratio and show very promising properties for a large number of * To whom correspondence should be addressed. Tel.: 040-232217454. Fax: 040-232-211299. E-mail: [email protected].

valuable applications. In a typical process, a polymer solution with certain characteristics is loaded in a syringe connected to a high dc voltage supplier. An electrostatic force is produced on the liquid surface, allowing the formation of a jet toward the opposed electrode. As the solvent evaporates, the polymer is deposited onto a collector screen or plate as nonwoven mats with very high specific areas. It has been reported that the characteristics of electrospun fibers depend on the solution properties such as viscosity, surface tension, conductivity, and also the operation conditions.23-25 The effect of increasing the concentration of the solution on fibers morphology and diameter has been investigated for many systems.26 In the present paper we try to obtain ultrafine CAP fibers or powders with high specific surface areas via the electrospinning procedure. Solutions of CAP in 2-methoxyethanol, an acetonewater mixture 85/15 (v/v), and a 2-methoxyethanol-acetonewater mixture 50/42.5/7.5 (v/v/v) are prepared. The study shows that by variation of the solvent system and the polymer concentration, powders and fibers of CAP with sizes in the submicrometer range and different morphologies can be easily obtained using a simple electrospinning laboratory setup. Experimental Section Both cellulose acetate phthalate investigated in this work and cellulose acetate (CA) used for CAP synthesis were prepared in our laboratory as follows: CA with DS ) 1.77 was obtained by partial hydrolysis of high-acetyl cellulose acetate at 60 °C for 32 h in a ternary system containing 20 wt % toluene, 67 wt % acetic acid, and 13 wt % water and in the presence of 5.7 wt % sulfuric acid catalyst (related to the initial amount of CA), as described elsewhere.27 Phthaloylation of CA was performed with phthalic anhydride in acetic acid medium by the following procedure: 10 g of CA were dissolved in 50 mL of glacial acetic acid, then 5 g of anhydrous sodium acetate catalyst, and 20 g of phthalic anhydride were added with vigorous stirring and the reaction system was heated at 70 °C and kept for 4 h at this temperature. The resulting solution was filtered and then pored into 500 mL of distilled water. The precipitated polymer was purified by several washes with distilled water and dried at room temperature. CAP thus obtained had a degree of phthaloylation of 0.70

10.1021/ie901427f  2010 American Chemical Society Published on Web 01/06/2010

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Figure 1. SEM micrographs of CAP nanofibers obtained from acetone-water 85/15 (v/v) at 10% (w/v) (a) and 12.5% (w/v) (b) polymer concentration.

and a degree of acetylation of 1.73 as determined by the method of Malm et al.28 Solutions of CAP were prepared in 2-methoxyethanol and mixtures of acetone-water 85/15 (v/v) and 2-methoxyethanolacetone-water 50/42.5/7.5 (v/v/v). The concentration of polymer solutions was varied between 10% and 35% (w/v). The solvents were of reagent grade and were used without further purification. The electrospinning parameters were as follows: voltage potential, 15-20 kV; tip-to-collector distance, about 15 cm; flow rate of the solution through the syringe, 1.5 mL h-1. The process was carried out in air at room temperature. CAP nanofibers were characterized by scanning electron microscopy (SEM; VEGA II SBH TESCAN). Micro-/nanoparticles of CAP were investigated by SEM with respect to their morphology and the particle size distribution curve for CAP powders was obtained by means of a system Mastersizer 2000 version 5.31, Malvern Instruments. Viscosity of CAP solutions was determined by means of a Brookfield SYNCHRO-LECTRIC Viscometer, model LVF. Surface tension measurements were performed on the automat tensiometer SIGMA 700 using the Wilhelmy plate method. The electrical conductivity was measured using a CDM 210 (Radiometer, Copenhagen) Conductometer.

Figure 2. Viscosity vs concentration of polymer solution in acetone-water mixture 85/15 (v/v).

Figure 3. Surface tension vs concentration of polymer solution in acetone-water mixture 85/15 (v/v).

Results and Discussion 1. Electrospinning of CAP from Acetone-Water Mixture. Solutions of CAP in an acetone-water mixture 85/15 (v/v) were prepared at room temperature and the polymer concentration was varied between 10% and 20% (w/v). Electrospinning of these solutions in the studied conditions gave fibers at polymer concentrations of 12.5% (w/v) (Figure 1b) or higher, whereas at lower concentrations beaded nanofibers in the submicrometer range were obtained (Figure 1a). It can be seen from Figure 1 that ultrafine fibers of 100-500 nm are produced in this solvent mixture at 12.5% (w/v), but some discontinuities were observed in polymer jet formation, which can damage the nanofibrous structure formation. The vapor pressure of acetone at 20 °C is as high as 181.7 mmHg and leads to rapid evaporation during electrospinning. This results in the formation of a plug at the tip of the syringe needle, which may interrupt the fibers formation if not eliminated from time to time. Increasing the concentration of the solution could not overcome this difficulty of the process.

Figures 2 and 3 present the solutions viscosity and surface tension, respectively, versus polymer concentration. It is observed that viscosity increases from 60 to 545 cP when increasing polymer concentration from 10% to 20% (w/v). Surface tension of 12.5% solution is 28.8 mN/m, as compared with that of the solvent (27.0 mN/m), but no significant variation of this property is observed in the studied concentration range (10-15 wt %). 2. Electrospinning of CAP from 2-Methoxyethanol. For these reasons, we have chosen to try electrospinning of CAP from 2-methoxyethanol, a suitable solvent for cellulose acetate and cellulose acetate phthalate with certain degrees of substitution. This solvent provides clear solutions of CAP for a wide range of concentrations. Furthermore, the solutions are acceptably viscous from an electrospinning point of view up to a concentration as high as 30-35% (w/v), rendering the possibility to investigate the influence of this parameter on the morphology of the electrospun products and on the evolution of the process.

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Figure 6. Schematic representation of the possible mechanism of the formation of CAP micro-/nanoparticles.

Figure 4. SEM micrograph of CAP micro-/nanoparticles obtained from 2-methoxyethanol solution at 12.5% (w/v) polymer concentration.

Figure 5. Particle size distribution of CAP micro-/nanoparticles obtained from 2-methoxyethanol solution at 12.5% (w/v) polymer concentration.

Because of a higher surface tension of 2-methoxyethanol (31.8 mN/m), as compared with that of the acetone-water mixture 85/15 (v/v) (27.0 mN/m), electrospinning of CAP from this solvent at low concentration (12.5%, w/v) yielded principally micro- and nanopowders (the process is electrospraying) (Figure 4). The particle size distribution curve for CAP powders obtained from 2-methoxyethanol solution at 12.5% (w/v) polymer concentration shows that 50% of the particles are smaller than 10 µm but there is a small fraction of particles in the submicrometer range (Figure 5). The smallest particles have about 500 nm. SEM analysis revealed the interesting morphology of CAP micro-/nanoparticles thus obtained: they look like void hemispheres with submicrometer width of their walls (Figure 4). Similar morphology was previously reported on electrospun polystyrene fibers by Lee et al.29 They pointed out that the formation of these hemispheres is a result of a combined action of three factors: polymer, solvent, and the electric force applied. We think that the polarity of the solvated polymer is the factor implied in the formation of such morphology. In the case of cellulose acetate phthalate, initially the surface tension tends to counteract the viscosity of the solution and to maintain the spherical shape of the drop. We can suppose that while flying to the negatively charged electrode (the collector plate), the drop is oriented in the electric field because of the polarity of the solvated polymer molecules and in this case the evaporation rate of the solvent is higher on the side directed to this electrode. This side becomes more rigid and determines the gradual formation of a void hemisphere with almost the same radius as the drop. By consequence, a bowl appears directed to the

positive electrode and finally the void hemisphere is produced. This particular shape increases the specific surface area of CAP micro-/nanoparticles. A tentative schematic representation of the process is given in Figure 6 but further investigation is necessary for more details of its mechanism. Electrospinning from 2-methoxyethanol proceeded continuously and the polymer jet was more uniform as compared with that of acetone-water solution at the same polymer concentration. For these reasons, higher concentrations of 2-methoxyethanol solutions were further investigated to find the optimal concentration for obtaining smooth nanofiber mats. It was observed that when increasing the polymer concentration from 12.5% to 35% (w/v), the morphology of the nanosized material gradually changes from particles to beaded nanofiber and finally to nanofiber mats (Figure 7), the proportion of particles decreasing with increasing the polymer concentration. It is known from previous reports26 that solution viscosity and surface tension are the main factors involved in the process. Their effects are somewhat opposite because viscoelastic forces counteract surface tension in the process. Thus, at low concentrations (low viscosity), surface tension is the dominant factor and favors the formation of beads. When the solution viscosity is increased, the formation of fibers without beads is expected. In the case of our polymer, the solution viscosity increases with concentration much more rapidly than the surface tension (Figures 8 and 9, respectively). At 25% (w/v) polymer concentration beaded nanofibers of CAP are observed (Figure 7a) and the shape of void hemispheres is partially preserved. At higher concentration, the number of beads diminishes, they become bigger, and their shape is more like a spindle than like hemispheres (Figure 7b). At the same time, the fibers diameter is larger as the solution viscosity is increased. When solution concentration is 30% (w/v) (Figure 7c) and 35% (w/v) (Figure 7d), few or no beads, respectively, are evidenced on SEM micrographs and fibers diameter is about 0.7-1.5 µm. Obviously, the viscosity, surface tension, and conductivity of the solutions determine the different morphologies observed when electrospinning CAP from the two investigated solvent systems. At low concentration of CAP (12.5%, w/v), no fibers but fine particles are obtained from 2-methoxyethanol because of the higher surface tension of the solution as compared with that in acetone-water mixture (85/15, v/v). Because of the presence of water, with a higher dielectric constant (80 at 25 °C) than 2-methoxyethanol (17.65 at 25 °C), more carboxylic groups of CAP are dissociated and the solution in this solvent mixture exhibits higher conductivity (49.8 µS/cm), which contributes, besides the lower viscosity, to the formation of fibers with smaller than 500 nm diameters. For comparison, solutions in 2-methoxyethanol have conductivities of 3.19-3.86 µS/cm (Figure 10) and fiber diameters as evidenced from Figure 7 were 0.7-1.5 µm. Therefore, electrospinning of CAP from this solvent proceeds more uniformly as compared with that of acetone-water mixture 85/15 (v/v), but a high concentration of polymer is needed to perform smooth filaments without beads.

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Figure 7. SEM micrographs of CAP beaded nanofibers and nanofiber mats obtained from 2-methoxyethanol solutions at 25% (a), 27.5% (b), 30% (c), and 35% (w/v) (d) polymer concentration.

Figure 8. Viscosity vs concentration of polymer solution in 2-methoxyethanol. Figure 10. Conductivity vs concentration of polymer solution in 2-methoxyethanol.

Figure 9. Surface tension vs concentration of polymer solution in 2-methoxyethanol.

3. Electrospinning of CAP from 2-Methoxyethanol-Acetone-Water Mixture 50/42.5/7.5. On the basis of these results, we carried out electrospinning of CAP from a mixture 1/1 of the two solvent systems discussed above, meaning a volume ratio of 2-methoxyethanol-acetone-water of 50/42.5/7.5. The characteristics of 25% (w/v) solution of CAP in this ternary system are as follows: viscosity, 1840 cP; surface tension, 35.6

mN/m; conductivity, 16.19 µS /cm. The stability of the solution jet during the process is quite good at this polymer concentration and smooth filaments without beads and fiber diameters of about 600 nm (smaller than those in 2-methoxyethanol) are obtained in these conditions (Figure 11), probably because of higher conductivity of the solution as compared with that in 2-methoxyethanol. Further research on solution rheology in relation to electrospinning conditions will display the influence of carboxylic groups on solution properties and fiber size, as reported earlier for other polymers.30 Besides, CAP enables formation of hydrogen-bonding associations, implying both carboxyl and hydroxyl groups which, depending on the solvent employed, may play an important part in the electrospinning process. It may be supposed that in 2-methoxyethanol (with lower dielectric constant) the carboxylic groups of CAP enable formation of hydrogen-bonding associations between macromolecules, which results in high viscosity (2850 cP at 25 wt % CAP concentration). The presence of water in the ternary mixture hinders aggregations between macromolecules, resulting in lower

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Figure 11. SEM micrograph of CAP nanofibers obtained from 2-methoxyethanol-acetone-water 50/42.5/7.5 (v/v/v) solution at 25% (w/v) polymer concentration.

viscosity (1840 cP at 25 wt % CAP concentration), and favors dissociation of carboxylic groups, thus increasing solution conductivity and leading to smaller diameters of the fibers. Conclusions Electrospinning of cellulose acetate phthalate with 0.70 degrees of phthaloylation and 1.73 degrees of acetylation gave fine particles or fibers depending on the solvent employed and on the concentration of polymer solution. The morphology of the electrospun CAP changed as a function of the solution characteristics like viscosity, surface tension, and conductivity. A low polymer concentration (12.5%, w/v) in an acetone-water mixture 85/15 (v/v) gave uniform fibers with diameters lower than 500 nm, whereas in 2-methoxyethanol at the same polymer concentration, only micro-/nanoparticles that look like void hemispheres have been obtained. When the concentration of CAP in 2-methoxyethanol is increased, the morphology of the electrospun CAP gradually changed and beaded fibers and fibers without beads were produced from solutions of 25% (w/v) and 35% (w/v), respectively. When 2-methoxyethanol-acetone-water 50/42.5/7.5 (v/v/v) is used as the electrospinning solvent system for CAP, smooth filaments without beads and fiber diameters of about 600 nm could be produced at concentrations of 25% (w/v). The electrospinnability of CAP from 2-methoxyethanolcontaining solvents was better than that from acetone-water mixture 85/15 (v/v). Acknowledgment The authors are grateful for the financial support of this work from MEdC - ANCS, Grant PC-D01-PT04-175/2005. Literature Cited (1) Fang, J.; Niu, H. T.; Lin, T.; Wang, X. G. Applications of electrospun nanofibers. Chin. Sci. Bull. 2008, 53, 2265. (2) Subbiah, T.; Bhat, G. S.; Tock, R. W.; Parameswaran, S.; Ramkumar, S. S. Electrospinning of nanofibers. J. Appl. Polym. Sci. 2005, 96, 557. (3) Liu, H.; Hsieh, Y.-L. Ultrafine fibrous cellulose membranes from electrospinning of cellulose acetate. J. Polym. Sci., Part B: Polym. Phys. 2002, 40, 2119. (4) Liu, H.; Tang, C. Electrospinning of Cellulose Acetate in Solvent Mixture N,N-Dimethylacetamide (DMAc)/Acetone. Polym. J. 2007, 39, 65. (5) Han, D.; Gouma, P. I. Electrospun bioscaffolds that mimic the topology of extracellular matrix. Nanomed.: Nanotechnol., Biol., Med. 2006, 2, 37. (6) Chen, L.; Bromberg, L.; Alan Hatton, T.; Rutledge, G. C. Electrospun cellulose acetate fibers containing chlorhexidine as a bactericide. Polymer 2008, 49, 1266.

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ReceiVed for reView September 11, 2009 ReVised manuscript receiVed December 9, 2009 Accepted December 15, 2009 IE901427F