Evaluation Study Of A Novel Transdermal Drug Delivery System Based On Silk Fibroin/PEO Composite Nanofibrous Matrice Fabricated By Green Process

Transdermal drug delivery system (TDDS) facilitates controlled release of active ingredients penetrating through the skin and into the systemic circulation. Drugs in such systems firstly escape via metabolism and maintaine stablility. Electrospinning is a simple process to fabricate ultrafine fibers with higher specific surface area and smaller pore size compared to commercial textiles make them excellent candidates for drug delivery. Electrospun nanofibers have been applied into the field of TDDS, acting as bone materials and carriers of the active ingredients. Ethosomes carriers are permeation-enhancing carriers, which could significantly promote drug delivered into skin in terms of quantity and depth. As a result, ethosomes-loaded electrospun nanofibers could release drugs in a rather smoother way and result in effectiveness on transdermal drug delivery systems.Silk fibroin (SF), a main component of silkworm silk, has unique properties including good biocompatibility, good oxygen and water vapor permeability, and low inflammatory response, which makes it an excellent biomaterial widely used in biomedical applications. And SF nanofibrous matrices can be fabricated through a green process of aqueous electrospinning. To improve the eletrospinnability of the aqueous SF solution and the mechanical properties of eletrospun products, poly ethylene oxide (PEO) was selected for blending based on its aqueous solubility and known biocompatibility.In this work, a novel ethosome-loaded regenerated silk fibroin/poly ethylene oxide composite(GSF-PEO/LA@Ethosome) nanofibrous matrice was successfully prepared based on a green electrospinning procedure. On this basis, the as-spun GSF-PEO/LA@Ethosome nanofibres were developed as carriers of LA for a TDDS. The in vitro release kinetic of the drug was investigated. The experimental contents are listed as follows:1. Preparation of GSF-PEO/LA@Ethosome nanofibrous matrice by green electrospinningA novel ethosome-loaded GSF/PEO nanofibrous matrice carried lipoic acid(LA) was successfully fabricated by a facile eco-friendly electrospinning process, without involving any poisonous materials or solutions. Scanning electron microscope (SEM) images showed that the ethosome-loaded GSF/PEO nanofibers had rounded shape and smooth surface, and the incorporation of ethosome didn’t significantly affect the morphology of the nanofibers. The data of Fourier transform infrared spectroscopy (FTIR) spectra suggested that the existence of ethosome in the GSF/PEO nanofibers. The laser scanning confocal microscopy (LSCM) images clearly showed that the ethosomes were distributed in the ethosome-loaded GSF/PEO nanofibers. X-Ray diffraction (XRD) analyses showed that the crosslinked nanofrber were still amorphous, and the structure of the regenerated silk fibroin transformed from hydrophilic silk I into hydrophobe silk Ⅱ after treated with75%(v/v) ethanol steam.2. The biocompatibility of GSF-PEO/LA@Ethosome nanofibers in vitroComprehensive characteristics of bio-safty including the attachment, spreading and proliferation of murine fibroblasts(L929) on electrospun nanofibers were studied by SEM, hematoxylin and eosin (H-E) staining. Results demonstrated that the cells could function biologically on the GSF-PEO/LA@Ethosome nanofibers. The nanofibrous structure could facilitate cell attachment. The dimethylthiazol diphenyltetrazolium bromide (MTT) assay illustrated that L929cells proliferated on the nanofibers is better than that on cover slips.3. The transdermal release kinetics of GSF-PEO/LA@Ethosome nanofibers in vitroA method of high performance liquid chromatography ultra-violet (HPLC-UV) was set up to determine LA quantitatively in transdermal accept liquid of the receiver. The electrospun GSF-PEO/LA@Ethosome nanofibrous matrice exhibited much higher accumulated release dose and release rate of LA than a normal regenerated silk fibroin/Poly ethylene oxide nanofibers(GSF-PEO/LA) without ethosomes. The rate and the total amount of the drug released increased with an increasing content of ethosomes. which resulted in sustained-release. The paraffin section of skin showed that the GSF-PEO/LA@Ethosome nanofibers exhibited much higher accumulated released dose of LA than GSF-PEO/LA nanofibers without ethosomes, and the ethosome carried LA could permeate into further deep layers of skin.In summary, a novel ethosome-loaded regenerated silk fibroin/poly ethylene oxide composite nanofibrous matrice has been developed in this work. With capacity of delivering various drugs into skin tissue and good biocompatibility, this product showed promising applications in the filed of transdermal drug delivery system.