Inverse micellar sugar glass (IMSG) nanoparticles for transfollicular vaccination

Transfollicular antigen delivery through the intact skin is an interesting new avenue for needle-free vaccination. The aim of this work was to evaluate the potential of surfactant based inverse micellar sugar glass nanoparticles (IMSG NPs) as a delivery system for such purpose. To this end, we evaluated the strength and type of immune response elicited after administration of IMSG NPs containing the model antigen ovalbumin (OVA) by intranasal, transfollicular or intradermal route. Furthermore, we explored the possibility of improving the immune response elicited by co-encapsulating the adjuvant bis-(3',5')-cyclic dimeric adenosine monophosphate (c-di-AMP) and OVA within one particulate carrier system. The study showed enhanced stability and encapsulation efficacy of the antigen when encapsulated in IMSG NPs in comparison to polylactic-co-glycolic acid (PLGA) and chitosan-PLGA NPs. Moreover, by transfollicular delivery, IMSG NPs showed enhanced follicular uptake in comparison to OVA solution or OVA-loaded chitosan-PLGA NPs. While the immune response stimulated after intranasal administration was negligible, significant humoral and cellular responses were observed after immunization via transfollicular and intradermal route. This holds particularly true when OVA and c-di-AMP were co-encapsulated in IMSG NPs, as compared to OVA±c-di-AMP solution or OVA-loaded IMSG NPs without adjuvantation. The results of this study underscore not only the potential of transfollicular vaccination, but also the need for optimized nanocarriers and adjuvants.