Needle-free vaccination is one the most important strategies to improve the immunization coverage and get better patient comfort which leads to increased compliance, without the requirement of trained personnel and the potential safety risks related to the traditional parenteral route. On the other hand, the skin is an organ attractive for vaccination because it has abundant APC found in their structure, leading to the use of lower amounts of antigen and the ability to be self-administered and a global decrease of the costs associated with immunization. The major obstacle to reach immunocompetent cells is the permeation characteristics of the stratum corneum. Overcoming this barrier is the aim for a successful transcutaneous vaccination. Nanosystems have shown efficient ability to get over biological barriers and they are striking means for transdermal delivery.
Considering this, the aim of this work is the design and development of new nanosystems based on biocompatible materials. These materials are arranged in nanocapsular or nanoemulsion structures, bearing therefore adjuvant properties. These nanocarriers were prepared by solvent displacement technique. These systems can include different materials such as polysaccharides (e.g: chitosan, hyaluronic acid), triterpenic saponins (obtained from an endemic Chilean tree (Quillaja saponaria)) and oils already licensed in some adjuvant formulations (e.g. α-tocopherol).
As shown in Figure 1, the different developed systems present nanometric size with a monomodal distribution and adequate surface charge. TEM images showed spherical shape and homogenous population without particle aggregation. These nanosystems allowed an efficient association of ovalbumin as a model antigen in its bioactive form. Stability studies showed that aqueous nanoparticle suspensions maintain their nanometric size over 12 months in storage conditions (4ºC) (Figure 2). Cell viability studies in RAW264.7 macrophages showed appropriate cellular toxicity up to high concentrations (Figure 3) and complement activation studies showed high interaction with the immune system (Figure 4). Preliminary ex vivo studies in pig skin have shown an improvement of model antigen transcutaneous administration.
In conclusion, we have successfully developed novel nanosystems with potential for transcutaneous vaccination, which can be considered as an interesting platform for the development of future needle-free vaccines.
Acknowledgment: FONDECYT initial project N° 11140797
