Transdermal Cancer Vaccine Using Antigen-Coating Nano Drug Carrier

Transcutaneous immunization using the skin's immune system is increasingly attracting attention. In contrast to conventional immunization by injection, transcutaneous immunization requires only topical application of antigens to the skin and is a simple, non-invasive immunization method that does not require medical personnel. Furthermore, the epidermal and dermal layers of skin contain an abundance of antigen-presenting cells (APCs) such as Langerhans cells (LCs) and dermal dendritic cells (dDCs). These APCs capture antigens, migrate to the lymph node from the skin, and then induce antigen-specific immunity by antigen presentation. Using the skin's immune system, transcutaneous immunization can offer a more effective method than subcutaneous (s.c.) or intramuscular injection. However, the major problem in transcutaneous administration is that the stratum corneum (SC), the outermost layer of the skin, serves as a hydrophobic barrier at the skin surface that hinders the penetration of hydrophilic biomolecules (M_w > 500 Da). Because most antigens are hydrophilic molecules, such as proteins and peptides, it is difficult to deliver antigens to APCs through the skin.

To overcome the SC barrier and induce immunity by topical application of antigens, various antigen formulations have been developed, including hydrogel patches, poly(lactic acid) nanoparticles, chitosan nanoparticles, and flexible liposomes. Our approach is to coat the hydrophilic antigens with hydrophobic surfactant molecules using water-in-oil (W/O) emulsification, followed by freeze-drying to produce oil-dispersible antigen–surfactant complexes. Because hydrophobic materials are more permeable through the hydrophobic SC than hydrophilic materials, oil dispersions of the complexes, namely solid-in-oil (S/O) nanodispersions, can improve the delivery of antigens into the skin. Using the S/O technique, we previously demonstrated antigen-specific antibody production by transcutaneous immunization, without physical enhancement or pre-treatment of skin. Furthermore, co-encapsulation of polyarginine as a skin penetration enhancer or CpG oligodeoxynucleotide as an immune adjuvant in S/O nanodispersions induced antibody production more effectively.

<>In this study, we applied the S/O nanodispersion technique to the induction of cancer immunity by transdermal delivery of cancer antigen. Cancer immunotherapy by activation of immune system against cancer has recently received attention for its feasibility in the treatment of malignancies with little toxicity. The key step for inducing the cancer immunity is the delivery of cancer-specific antigens to DCs, followed by the antigen-presenting by the DCs. We prepared S/O nanodispersions bearing ovalbumin (OVA) as a model cancer-antigen for efficient transdermal OVA delivery. Our investigation revealed the ability of this approach to induce antigen-specific cellular immune responses against cancer by evaluating the growth of OVA-bearing tumors and the production of cytokines from splenocytes. Inhibition of OVA-bearing tumor growth was achieved, demonstrating the applicability of S/O nano carriers to the induction of cancer immunity.