Galactosylated chitosan-modified ethosomes combined with silk fibroin nanofibers is useful in transcutaneous immunization

Abstract

Transcutaneous immunization (TCI) has the advantages of avoiding the liver first-pass effect, good compliance and convenient use compared with the traditional oral or injection vaccination. However, the stratum corneum (SC) of the skin is the main obstacle that limits the entry of antigen molecules into the epidermis for activating dendritic cells (DCs). In the present study, the hyaluronic acid (HA) and galactosylated chitosan (GC) modified ethosome (Eth-HA-GC) was prepared through layer-by-layer self-assembly method. Eth-HA-GC has good stability and can be effectively phagocytosed by the bone-marrow-derived DCs (BMDCs) in vitro. The ovalbumin (OVA) loaded Eth-HA-GC (OVA@Eth-HA-GC) can promote BMDCs' expression of CD80, CD86 (DCs maturation-associated marker molecules), TNF-α, IL-2 and IL-6. Subsequently, a novel OVA@Eth-HA-GC-loaded silk fibroin (OVA@Eth-HA-GC/SF) nanofibrous mats were fabricated through green electrospinning. The OVA@Eth-HA-GC/SF mats exhibit good transdermal performance in vitro. Transdermal administration with OVA@Eth-HA-GC/SF mats induced the serum anti-OVA-specific IgG and increased the expression of IFN-γ, IL-2 and IL-6 by spleen cells in vivo. Furthermore, the use of OVA@Eth-HA-GC/SF mats evidently inhibited the growth of EG7 tumor in the murine model. These results demonstrate the OVA@Eth-HA-GC/SF mats can effectively stimulate the immune response to OVA through transdermal administration. In conclusion, the antigens@Eth-HA-GC/SF mats is a promising TCI system.

Keywords: Dendritic cells; Electrospinning; Ethosome; Galactosylated chitosan; Hyaluronic acid; Silk fibroin; Transcutaneous immunization.