Hybrid electrospinning of blend nanofibrous drug-releasing membrane for wound dressing

The controllable drug-releasing is the key to the application of wound dressing and other bioremediation membrane. In this paper, a hybrid electrospinning method was utilized to fabricate the PVP/PVAc blend nanofibrous membrane. The effects of processing parameters were investigated on the morphology, diameter and dispersion of nanofibers. Drug release test was carried out for PVP/PVAc nanofiber membranes with different mass ratio, showing excellent drug-releasing performance for the blend nanofiber membranes.


Introduction
Nanofibrous membrane has displayed great advantages in various fields, which has attracted attention from all over the world to increase the potential applications [1,2] .The manufacturing methods of nanofibers are diverse, including the gas phase growth method, the split multicomponent fiber spinning method, the phase separation method, the melt spray method, the tensile method, the template method, the electrospinning method, et al.Among these methods, electrospinning stands out for its high efficiency, simple equipment, and excellent ability to directly and continuously produce nanofibers from polymers.As a result, it is extensively utilized in the nanofiber manufacturing industry [3] .
The nanofibers prepared by electrospinning were closely resembled to the fiber structure of the natural extracellular matrix, which contributes to the promotion of cell adhesion and proliferation.Moreover, the high specific surface area and porosity of nanofibers facilitates the exchange of liquid and gas.The release time and action cycle of drugs can be controlled during the wound healing process, which is beneficial for accelerating wound healing and minimizing scar formation [4] .The blood concentration change curve was shown in Figure 1.In this paper, the nanofiber dressing of a sustained-release drug was prepared, which could realize the drug releasing at a certain speed at a fixed site on the body surface within the required time range, so as to achieve the purpose of curing a certain wound without causing side effects of the drug, as depicted in Figure 2. Polyvinyl pyrrolidone (PVP) was chosen for its exceptional colloidal protection and membrane formation properties, as well as its biocompatibility and low toxicity.Similarly, polyvinyl acetate (PVAc) is an inert polymer without adverse reactions in living tissues, making it suitable for various medical applications.Then, the control of drug release can be achieved through the use of hybrid electrospinning fiber membranes.Additionally, the diameter and dispersion of the blend fiber membranes can impact the initial release and release rate of the drug.The influence of various process parameters on the fiber membranes was investigated, so as to establish a foundation for the development of a nanofibrous wound dressing that can effectively control the release of drugs.

Experiment Process
The experiments were carried out on an electrospinning equipment (NL-E-ES-2, Narai).The temperature was maintained at 30℃, with a relative humidity of 50% RH.The receiving distance was set at 10 cm.The blend nanofibrous membrane was prepared through hybrid electrospinning using the two different polymer solutions mixed at different mass ratios with varying concentrations and applied voltages to modify the nanofibrous membrane.

Morphology and structural characterization of the fibers
The PVP, PVAc and PVP/PVAc nanofiber samples were observed by SEM (Type Sirion200，FEI, Inc.), and the surface topography of the images was analyzed by ImageJ software.

Drug release test
The electrospun nanofiber membrane samples were cut into evenly sized fragments, and placed into a conical flask with 40 mL PBS (pH=7.4)solution.The conical flask was placed in a constant temperature oscillator at the temperature of 37ºC and oscillation speed of 150 rpm.Then, the samples were removed for drying after a specific time period to measure the weight loss.

Weight loss % = − d × 100%
where M is the initial dry mass of sample, Md is the dried mass of immersed sample in buffer medium.

PVP nanofibers
The formation of a jet in a polymer solution is caused by the electric field force surpassing the surface tension.Changing the applied voltage will alter the magnitude of the electric field force, thereby affecting the prepared nanofiber morphologies.
The PVP nanofiber morphology of with solution mass fraction of 8 wt%, 10 wt% and 12 wt% under applied voltages of 5 kV, 6 kV, 7 kV, and 8 kV were shown in Figure 3, 4 and 5 respectively.When the solution concentration was too low, it was difficult to obtain nanofibers with good morphology.The polymer liquid was elongated under the action of electric field force.With the increase of solution concentration, the increase of solution viscosity enhanced the intermolecular entanglement, resulting in the more stable jet, more smooth and uniform nanofibers.
Furthermore, when the applied voltage was too low, there was little charge on the solution, making it difficult for the electric field force to overcome the surface tension.As depicted in Figure 3(b), there was a tangle presented between the nanofibers.Conversely, when the voltage was too high, the droplets carried an excess of charges, resulting in an unstable jet formation during the electrospinning process.As illustrated in Figure 4(d), the PVP nanofibers exhibited noticeable unevenness under the applied voltage of 8 kV.
The PVP/ PVAc fiber morphology with PVP and PVAc mass ratios of 5:5; 6:4; 7:3 under applied voltages of 6 kV, 8 kV, 10 kV, and 12 kV were shown in Figure 6, 7 and 8 respectively.The increasing applied voltage raised the strength of the electric field, resulting in more charges in the solution, higher electrostatic repulsion, and larger tensile force.Under the dual action of electrostatic repulsion and tensile force, the strain rate of the jet increased, leading to thinner nanofibers.

Figure 2
Figure 2 Drug-releasing system for wound repair.

Figure 9
Figure 9 Effect of the type of polymer/the drug content on the weight loss(%) of PVAc, PVP, 5:5 blend and 4:6 blend nanofiber membrane.