The transcutaneous immunization is a promising technique of vaccination which the formulation containing an antigen is applied to the skin to induce immune response without producing local or systemic toxicity. It is painless and avoids all the risks caused by the use of needles. The success of this type of immunization is due to the presence of antigen-presenting cells in the viable epidermis which are potent stimulators of T lymphocytes inducing the immune response. Delivery systems such as liposomes and physical methods such as electroporation have been studied to help the antigen to transpose the barrier imposed by the stratum corneum, reaching the viable epidermis at high concentrations. The nanocarriers are also used to protect the antigen from degradation, but they do not penetrate intact the skin and so the electroporation increases the amount of antigen that crosses the skin due to application of a 1000 V electrical pulse. Obviously this strategy causes great discomfort to the patient and does not direct the release of antigen into the skin but through it. Surprisingly, the study of iontophoresis, another physical method which also uses electric current but with intensity more than 1000 times weaker than in electroporation, has been little explored for transcutaneous immunization. The appropriate control of formulation and iontophoretic parameters (such as current application time, polarity and conductivity) could increase the penetration of antigens for the specific location where the skin antigen-presenting cells are present without causing irreversible damage to the cells. In addition to it, iontophoresis may promote the penetration of nanoparticles into the skin and thus increase penetration not only of the antigen but also of the carrier system that protects the drug against degradation in the skin. As has been observed in cell culture studies that metal nanoparticles acts as a good immune adjuvant, the iontophoretic application at formulations containing the antigen and metal nanoparticles can possibly increase the penetration of both to the skin leading to an effective transcutaneous immunization. Therefore the objectives of this study are two: 1) to study the influence of transcutaneous immunization using iontophoresis for a model antigen (ovalbumin) encapsulated in liposomes (to ensure the stability of antigen in contact with the skin) and 2) verify the influence of metal nanoparticles at (a) stability of liposomes during the iontophoresis application, (b) the efficiency of electric current and, consequently, increased penetration of the antigen by iontophoresis and (c) the immune response induced . The innovative nature of this proposal lies mainly in the study for the first time of the iontophoresis influence on transcutaneous immunization with nanoparticulate systems (liposomes and metal nanoparticles). The iontophoresis itself can also function as an immune adjuvant but this has never been studied.
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