Preparation And Characterization Of Silk Electrospun Fibers Containing Drug-loaded Microspheres

Silk fibroin is a naturally protein polymer with excellent biocompatibility,remarkable biodegradability, no-toxic and nonirritating. Due to its uniqueproperties, silk fibroin has been widely used in the field of drug delivery. It iseasy to be processed into multiple forms including films, nanofibers, hydrogels,nanospheres and porous materials. Among these forms, nanospheres haveattracted much attention of researchers due to their large specific surface areaand high surface energy, easy to diffuse and response quickly to external stimuli.In this paper, silk nanospheres were prepared by self-assembly with silk fibroinas raw materials. Then, drug-loaded silk fibroin nanospheres were obtained byincorporating curcumin into the nanospheres. In recent years, with thedevelopment of controlled sustained drug delivery technology, it has beennoticed that there are problems of initial burst release and short efficacy time fora single drug-loaded form. Therefore, the exploring and investigating of composite carriers has become new focus of drug-loaded research. In the presentstudy, the composite carrier of silk fibroin electrospinning nanofibers containingsilk nanoparticles were successfully obtained by encapsulating drug-loaded silknanospheres in fibers with electrospun technology. In addition, the propertiesand influence parameters of the composite carriers were also investigated.First of all, silk fibroin nanospheres were prepared with the cooperationeffect of ethanol and freezing. The effects of ethanol additives content, silkfibroin concentration, freezing time on the formation and morphology of silkfibroin nanospheres were investigated. It was founded that the size andpolydispersity of silk nanospheres decreased with increasing the content ofethanol additives, and increased with the concentration of silk fibroin. Theresults showed that silk fibroin nanospheres with predictable and reproduciblesize, in a controllability size range from0.2to1.8μm, can be prepared byadjusting ethanol additives content, silk fibroin concentration and freezing time.Moreover, the drug loading, encapsulation efficiency and controlled-releaseproperty of curcumin-loaded silk fibroin nanospheres were studied. Theformation, morphology, structure, size and in vitro drug release of drug-loadedmicrospheres were also investigated by Scanning Electron Microscopy (SEM),Fluorescent Microscope, Dynamic Light Scattering measurements (DLS) andX-ray Diffraction (XRD). It was found that the produced microspheres wereglobular particles with a range of210~320nm in diameter and highly uniformwith the PDI around0.170. The diameters of drug-loaded microspheres increased with silk fibroin concentration, and decreased with the initialconcentration of the curcumin. The encapsulation efficiency of nanoparticleswas up to40.27%and the loading efficiency can be1.22%. Drug release in vitroshowed that curcumin-loaded silk fibroin microspheres had obviouslysustained-release property and the release speed of curcumin could be controlledby adjusting the content of ethanol.Lastly, silk fibroin nanospheres/silk fibroin electrospun composite fiberswere successfully prepared by electrospinning technology. In the paper, the bestelectrospinning parameters for silk solution of concentration at30wt%, pH at6.0were discussed. The morphology of drug-loaded nanospheres and compositecarriers, the diameters and distribution of composite fibers, particle sizes ofmicrospheres and the hydrophobicity of composite materials were characterizedby SEM, DLS, Fluorescent Microscope, confocal laser scanning microscopy(CLSM) and contact angle measurement. The results showed that the produceddrug-loaded nanospheres were all in fine spherical shape with an average meanabout251nm. Silk fibroin solution has the best spinnability when the appliedvoltage, the flow rate and distance between the needle and the collector wereoptimized at34~36kV,15μL/min and15cm, respectively.Silk fibroin nanospheres were successfully encapsulated in silk fibroinelectrospun fibers forming core-sheath structure. The produced compositecarriers showed smooth surface and the average mean was about910nm,standard deviation about0.28. The diameters and hydrophobicity of composite carriers increased after water vapor annealing.In general, the method of self-assembly for preparing drug-loaded silkfibroin microspheres was simple and productivity. The produced microsphereswere stable and without aggregation in aqueous solution. The preparedcomposite carriers of silk fibroin electrospun fibers containing drug-loadedmicrospheres provided a novel approach for retarding the initial burst releaseand also offered a new carrier form for silk fibroin applied in drug deliverysystem.