Fabricat And Evaluative Study On The Ethosome/Silk Fibroin Composite Nanofibrous Matrices Used As Transdermal Delivery System

Transdermal delivery system(TDDS)is a drug-controlled-release system which can provide an effective blood concentration and then be efficient for treatment or prevention of disease through the skin. Its advantages include: protecting the drugs from first pass effect of the liver and digestion of gastrointestinal tract, and thus improve their efficacy; reducing the frequency of drug administration for the duration of drugs activity; maintaining a constant plasma concentration and reducing side effects; convenient for use and can be administered and terminated at any time.Because the skin’s stratum corneum is an impenetrable barrier, the transdermal rate of most drugs is difficult to achieve treatment requirements. Therefore, finding an effective method to promote drug through the skin is the key to TDDS development. To find an ideal effect of drug transdermal absorption, our previous study fabricated a TDDS based on silk fibroin / ethosomes composite nanofibrous. This TDDS not only possess the silk fibroin’s good benefial for skin and the nanofibrous’ large specific surface area, but also has the ethosomes’ excellent transdermal ability. The data in vitro showed that the novelsystem has a good performance on drug transdermal delivery. In this work, we evaluate the performance of the novel TDDS by more systematic study, and the contents are listed as follows:(1) The fibre diameter of the ethosomes / silk fibroin composite nanofibrous is about 600±30nm, and the cell viability assay shows that this composite nanofibrous had good biocompatibility;(2) CY7, bovine serum albumin(BSA) and near-infrared fluorescence expression plasmid(piRFP) were used as model drugs respectively( their corresponding molecular weights is 102, 104 and 106 respectively). The transdermal performance of the drugs-loaded ethosomes / silk fibroin composite nanofibrous matrice were then evaluated in vitro. The results showed that the accumulate release of the model drugs reached 67%、24% and 21% respectively. Dermal tissue paraffin section assay confirmed that the drugs penetrate through the stratum corneum deep into the dermis.(3) The in vivo imaging technique was utilized to observe the effect of our novel TDDS to promote the transdermal delivery of different molecular weight drugs. The results showed that the model drugs(CY7、BSA-CY7 and piRFP) enter into the body through the skin of the nude rats. Besides, the piRFP was expressed into proteins in vivo, which demonstrate that our TDDS can effectively promote the transdermal penetration of macromolecular drugs without damaging their function.In summary, the TDDS based on the ethosome / silk fibroin composite nanofibrous matrice showed excellent percutaneous performance. It can effectively promote the macromolecular drugs penetrating and release through skin, and thus possess a promising application in transdermal immunity and other biomedical fields.