Drug-loaded Coaxially Electrospinning Nanofibers As Burn Dressings

A deep partial-thickness burn injury is one of the most common burns with wound swelling and accompanied by blisters. Many topical drug formulations were often used in clinic. One of the most widely used was burn dressings, which can provide a suitable micro environment for wound healing.Electrospinning is one of the most rapid and effective production methods to prepare nanofibres. The electrospinning nanofibers were uniform with longer length, and higher porosity and ratio of surface area to volume. These characteristics are similar to the structure of the extracellular matrix. Therefore, nanofibers as wound dressing were particularly suitable to promote wound healing.As we know, both of sodium alginate and chitosan are beneficial to wound healing based on good exudate adsorption and antibacterial function. However, the two polymers cannot be mixed in one formulation previously due to electrostatic aggregation. A novel coaxially electrospinning nanofiber composed of sodium alginate, polyvinyl alcohol(PVA) and chitosan were designed and prepared in our study to treat deep partial-thickness burn injury. The research contents were as the followings.1. Preparation of the coaxially electrospinning nanofibersIn this study, sodium alginate and PVA were chosen for the shell-forming material, chitosan for the core-forming material to prepare a novel coaxially electrospinning nanofiber. The coaxial nanofibers can absorb a great deal of wound exudates based on the high water adsorption capacity of alginate and inhibit microorganism growth on the wounds based on the antibacterial function of chitosan. The final formulation of coaxially electrospinning nanofibers consisted of 7% PVA and 0.8% alginate in the shell-forming solution and 3% chitosan in the core-forming solution. During electrospinning, a voltage of 23 k V was applied between the needle and the collector. The acceptance distance was 15 cm and the pushing rate of the shell and core solutions was 0.8, 0.2 ml/h, respectively. The coaxial nanofibers showed smooth surfaces, and uniform diameter distribution. The average diameter was 373.74±90.74 nm.2. Characteristics of coaxially electrospinning nanofibersThe typical core-shell structure of coaxial nanofibers was observed by Transmission electron microscope(TEM). The TEM images showed that the coaxial nanofiber had a uniform core-shell structure with the outer and inner diameter of 166.8, 99.2 nm, respectively. X-ray diffraction(XRD) and Fourier transform infrared spectrum(FTIR) showed the bonding interaction of the components in the coaxial nanofibers. This was different with that of the physical mixtures. Compared to the alginate/PVA or chitosan/PVA nanofibers, the water absorption capacity of alginate/PVA/chitosan coaxial nanofibers was significantly higher. Water absorption ratio increased with prolonged time and reached nearly saturation after 24 h. The loose and porous nanofibers changed to the viscous and soft film following water absorption. The coaxial nanofibers showed the clear inhibition zones for S. aureus and and P. aeruginosa. In comparison, the alginate/PVA nanofibers did not show any antibacterial effect.3. Preparation of drug-loaded coaxial nanofibers and their characteristicsAsiaticoside-loaded coaxial nanofibers were prepared with smooth surfaces, uniform diameter distribution and the average diameter of 433.37±75.47 nm. Asiaticoside was determined directly using an Agilent 1260 high performance liquid chromatographic(HPLC) system(USA). The detailed HPLC conditions were as the followings: Diamonsil? C18-ODS HPLC columns(5 μm,250 mm × 4.6 mm), mobile phase consisted of acetonitrile/water(29:71, v/v), the flow rate of 1.0 ml/min, and the detection wavelength of 205 nm. The retention time was about 9.8 min and the linear range was within 10-400 μg/ml. In the drug release experiments, the drug-loaded composite nanofibers showed much faster drug release rates than the drug-loaded coaxial nanofibers. Simulation may reveal the mechanisms of drug release. The highest r2 values of the coaxial nanofibers appeared as the Ritger-Peppas equation. The n in Ritger-Peppas exponent models showed that Fick’s diffusion dominated drug release from nanofibers.4. Pharmacodynamics of the coaxial nanofibers in deep partial-thickness burnsDeep partial-thickness burn wounds of rats were established with an electrical heating instrument. The rats were scalded for 8 s with the constant temperature(80 °C) and pressure(500 g). This procedure was conducted to create deep partial-thickness burn injury. The alginate/PVA/chitosan coaxial nanofibers showed enhanced wound healing effect according to appearance, wound area, and pathological investigation. Based on evaluation of a series of cytokines, the coaxial nanofibers were demonstrated to improve angiogenesis and vasculogenesis by upregulation of vascular endothelial growth factor(VEGF), cluster of differentiation 31(CD31) and proliferating cell nuclear antigen(PCNA), inhibit the inflammatory factors including tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and increase fibroblast proliferations and collagen synthesis. The coaxial nanofiber is a novel and promising wound dressing for the treatment of deep partial-thickness burn injury.