Iontophoresis on transcutaneous immunization with nanoparticulate delivery systems

• Grant number: 12/05177-3
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2012
• End date: June 30, 2014
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Renata Fonseca Vianna Lopez
• Grantee: Renata Fonseca Vianna Lopez
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 13/50334-2 - Immunolipossomes for skin diseases application: influence of physical penetration enhancement methods, AP.R

Abstract

Transcutaneous immunization is a promising technique of vaccination in 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. Electroporation increases the amount of antigen that crosses the skin due to the application of very high (1000 V) electrical pulse. Obviously this strategy causes great discomfort to the patient and does not target the skin itself but the systemic circulation. Surprisingly, the study of iontophoresis, another physical method that also uses an 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 located without causing irreversible damage to the cells. In addition, iontophoresis may promote the penetration of nanoparticles into the skin and increase not only the antigen penetration but also that one of the nanoparticle. Metal nanoparticles have been shown to be good immune adjuvants when studied in cell cultures. Therefore, the iontophoretic delivery of 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 the iontophoresis on the transcutaneous immunization using a model antigen (ovalbumin) encapsulated in liposomes (to ensure the stability of antigen in contact with the skin) and 2) to verify the influence of metal nanoparticles on the (a) stability of liposomes during the iontophoresis, (b) efficiency of electric current and, consequently, antigen penetration 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). Iontophoresis itself can also function as an immune adjuvant but this has never been studied too. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BERNARDI, DANIELA S.; BITENCOURT, CLAUDIA; DA SILVEIRA, DENISE S. C.; DA CRUZ, ESTAEL L. C. M.; PEREIRA-DA-SILVA, MARCELO A.; FACCIOLI, LUCIA HELENA; LOPEZ, RENATA F. V.. Effective transcutaneous immunization using a combination of iontophoresis and nanoparticles. Nanomedicine-Nanotechnology Biology and Medicine, v. 12, n. 8, p. 2439-2448, NOV 2016. (12/05177-3, 14/07125-6, 11/13307-1, 14/22451-7)