A modified coaxial electrospinning process was developed for creating drug-loaded composite nanofibers. Using a mixed solvent of ethanol and N,N-dimethylacetamide as a sheath fluid, the electrospinning of a codissolving solution of diclofenac sodium (DS) and Eudragit L100 (EL100) could run smoothly and continuously without any clogging. A series of analyses were undertaken to characterize the resultant nanofibers from both the modified coaxial process and a one-fluid electrospinning in terms of their morphology, physical form of the components, and their functional performance. Compared with those from the one-fluid electrospinning, the DS-loaded EL100 fibers from the modified coaxial process were rounder and smoother and possessed higher quality in terms of diameter and distribution with the DS existing in the EL100 matrix in an amorphous state; they also provided a better colon-targeted sustained drug release profile with a longer release time period. The modified coaxial process not only can smooth the electrospinning process to prevent clogging of spinneret, but also is a useful tool to tailor the shape of electrospun nanofibers and thus endow them improved functions.
The physical properties, such as shape, size, mechanical properties, surface texture, and compartmentalization, profoundly impact the function of a nanobiomaterial and thus raise important questions for the design of its next generation [
Coaxial electrospinning is a power tool for generating core-sheath nanofibers through manipulating two fluids using a concentric spinneret [
Here, different from above-mentioned applications, the modified coaxial electrospinning was exploited as a useful tool for manipulating the shape of resultant nanofibers and improving their functional performance of colon-targeted sustained release. Eudragit L-100 (EL100), a well-known methacrylate-based copolymer developed by the Röhm Company in Germany and a common excipient used in the pharmaceutical field, was exploited as the filament-forming matrix here. It has been widely used for the formulation of different oral dosage forms (e.g., tablet coating, tablet matrix, microspheres, and nanoparticles) for colon-targeted drug delivery [
EL100 was supplied by Rohm GmbH & Co. KG (Darmstadt, Germany). DS was purchased from Hubei Biocause Pharmaceutical Co., Ltd. (Hubei, China). Methylene blue, N,N-dimethylacetamide (DMAc), and anhydrous ethanol were provided by Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). Water was double distilled just before use. All other chemicals and reagents were of analytical grade.
A codissolving solution of EL100 and DS was prepared and used as the core fluid, which consisted of 15% (w/v) EL100 and 2% (w/v) DS in a mixture of ethanol : DMAc (with a volume ratio of 9 : 1), meaning 11.8% of DS in the solid products. The sheath mixed solvents contained DMAc and ethanol at a volume ratio of 30 : 70. The prepared nanofibers are referred to as F2. To observe the electrospinning process, 5 ppm methylene blue was added to the core solution.
A homemade concentric spinneret was used to conduct the coaxial electrospinning processes. Two syringe pumps (KDS100 and KDS200, Cole-Parmer, IL, USA) and a high-voltage power supply (ZGF 60 Kv/2 mA−1, Shanghai Sute Corp., Shanghai, China) were used for electrospinning, which was performed under ambient conditions (25 ± 2°C; 57% ± 6% relative humidity). The coaxial electrospinning processes were recorded using a digital video recorder (PowerShot A490, Canon, Tokyo, Japan). After optimization, the applied voltage was fixed at 15 kV and the fibers were collected on an aluminum foil 20 cm from the spinneret.
Using the same apparatus of coaxial electrospinning and under the same conditions, a one-fluid electrospinning of the core solutions was implemented through adjusting the flow rate of the sheath fluid to 0 mL/h. The prepared nanofibers are referred to as F1, which was investigated as a control.
The morphology of the nanofibers was examined using an S-4800 field-emission scanning electron microscope (FESEM, Hitachi, Tokyo, Japan). Prior to examination, the samples were platinum sputter-coated under nitrogen atmosphere to render them electrically conductive. The average fiber diameter was determined by measuring their sizes in FESEM images at more than 100 different places using NIH Image J software (National Institutes of Health, MD, USA). Cross-sections of the fiber mats were prepared by placing them in liquid nitrogen and manually breaking them before platinum coating. The topographies of raw material particles and drug-loaded nanofibers were observed under cross-polarized light using an XP-700 polarized optical microscope (Shanghai Changfang Optical Instrument Co. Ltd., Shanghai, China).
XRD patterns were obtained over the 2
The
A schematic diagram of the modified coaxial electrospinning process is shown in Figure
The schematic diagram of the modified coaxial electrospinning (a) and the homemade concentric spinneret (b).
Observations of the traditional single fluid electrospinning (a) and the modified coaxial process ((b) to (d)).
Digital images about the modified coaxial electrospinning are shown in Figures
The morphologies of surface (Figures
Surface and cross-section morphologies of F1 nanofibers from the traditional electrospinning.
Surface and cross-section morphologies of F2 nanofibers from the coaxial process.
The traditional one-fluid electrospinning shares characteristics of both electrospraying and conventional solution dry spinning. During the process, ethanol evaporated very quickly. This would make the electrospinning process very sensitive to small changes in the environment and thus resulted in nanofibers with a wide range of sizes and also generate a solid “skin” on the surfaces of collected fibers with some solvent still trapped inside the fiber bodies. After spinning, the solvent contained in the fibers diffused out into the atmosphere, and the resulting barometric pressure distorted the cylindrical fibers to the flat morphology, whereas the modified coaxial process shares characteristics of both electrospraying and conventional solution wet spinning to some extent. It could provide a stable and robust core-sheath interface for the core EL100-DS solution when it was drawn in the electrical field. This not only enables the core solutions to have a longer time period of electrical drawing force in the fluid phase [
The presence of numerous distinct peaks in the XRD patterns of the fibers suggested that DS was present as crystalline material with characteristic diffraction peaks, as also demonstrated by the colorful images of their crude particles under polarized light (Figure
XRD patterns (a) and ATR-FTIR spectra (b) of the components and their composite nanofibers.
Compared to the spectra of pure DS and EL100, there are significant changes in the spectra of the nanofibers F1 and F2 (Figure
To evaluate DS release profiles from the medicated nanofibers,
At a pH of 6.8, both the nanofibers F1 and F2 exhibited a sustained drug release profile. However, nanofibers F2 from the modified coaxial process provided a better sustained release profile with a longer time period. Compared to nanofibers F2, nanofibers F1 had (1) a larger burst release in the 3rd hr (i.e., 55.7% to 41.2%) which is disadvantageous to sustained release; (2) a shorter time when 50% of the contained drug was freed (i.e., 2.8 hr to 3.4 hr); and (3) a longer time period of the undesired “tailing off” release (i.e., only released 1.9% after the 5th hr). Both nanofibers F1 and F2 were nanocomposites with the drug DS homogeneously distributed on the polymer matrix EL100. The sustained drug release profiles should be attributed to their difference in physical shapes, which determined the diffusion or erosion distance for water diffusing into the nanofibers and the drug diffusing into the dissolution medium. Showed in Figure
To further investigate the drug controlled release mechanism, the drug release profiles from the nanofibers F1 and F2 were analyzed using the Peppas equation [
A modified coaxial electrospinning process in which only an unspinnable mixed solvent system was used as a sheath fluid has been successfully developed to produce medicated EL100 nanofibers. FESEM observations revealed that the modified coaxial electrospinning process is an effective method for manipulating the nanofibers’ shape and structural uniformity. The use of the surrounding solvents facilitated the drawing of the core DS/EL100 codissolving fluid jet, producing round composite fibers with a finer average size of 650 ± 130 nm under a sheath-to-core flow rate ratio of 0.1, whereas the fibers from the one-fluid electrospinning process had a flat morphology with an average width of 1280 ± 330 nm. However, both fiber types were similar in that the drug DS dispersed in an amorphous state in the filament-forming matrix EL100 and could be freed in a sustained manner through a combination of erosion and diffusion mechanisms in a neutral condition. Nonetheless, the fibers from the modified process exhibited a better colon-targeted sustained release performance than those from the single fluid electrospinning process in terms of release time period. The modified coaxial electrospinning process reported herein clearly extends the capability of electrospinning to fabricate functional polymer fibers with better structure and morphology and enhanced functional performance.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This work was supported by the National Science Foundation of China (nos. 51373101 and 51373100), the Natural Science Foundation of Shanghai (no. 13ZR1428900), the Key Project of the Shanghai Municipal Education Commission (no. 13ZZ113), and the Innovation Project of the College Student Fund Committee (no. SH2013167).