Stimuli-responsive double emulsions for transcutaneous delivery of vaccines
Description
This study is a first step toward the development of a vaccine cream that will be applied to the skin in the same way as cosmetic formulations. Skin may be a potent immunological induction site since it acts as an immune barrier by its immunocompetent cells. Vaccines that target the skin only require delivery through the outermost skin layer (stratum corneum), which is an effective but fragile barrier that can be disrupted by hydration. Therefore, several studies have already shown strong systemic and mucosal immune responses following topical application. Transcutaneous immunization has the potential to make vaccine administration easier and cheaper, while maintaining efficiency and safety, which would facilitate the implementation of worldwide mass vaccination campaigns and provide the means for a fast response to terrorist bio-attacks Our main goal was to provide a novel stimulus-responsive water-in-oil-in-water (W1/O/W2) double-emulsion system for vaccine administration to the skin. By use of fluorescence capillary video-microscopy we prepared and monitored individual W1/O/W2 double-emulsion globules subjected to pH and temperature stimuli in order to control the release of model drugs (FSS) and proteins (FITC-BSA), respectively: (1) We proposed a method to fine-tune release of small drugs from double emulsions. Complexation of the active species with oppositely-charged nanohydrogels---confined within the emulsion globules---prevented leakage until presence of acid disrupted such complex and activated release. (2) The delivery of proteins requires an external stimulus that breaks the emulsion globules. We demonstrated that this can be achieved by temperature swings that cause the oil phase to freeze and thaw. Finally, a model W1/O/W2 double emulsion was developed in bulk which remained stable during months of storage at low temperature and efficiently released the encapsulated protein (FITC-13SA) upon temperature increase According to the double-carrier concept introduced here, the proposed W1/O/W2 double emulsion may be used in combination with cationic nanohydrogels. Thus, we suggest that the double emulsion would protect the vaccine during storage and facilitate topical application, while the hydrogel nanoparticles enhance its delivery to the antigen-presenting cells---located below the stratum corneum---so that an immune response is generated