Vaccination faces many challenges nowadays, and among them the use of adjuvant\nmolecules and needle-free administration are some of the most demanding. The combination of\ntranscutaneous vaccination and nanomedicine through a rationally designed new-formulation could\nbe the solution to this problem. This study focuses on this rational design. For this purpose,\nnew hyaluronic acid nanocapsules (HA-NCs) have been developed. This new formulation has an oily\nnucleus with immunoadjuvant properties (due to alpha tocopherol) and a shell made of hyaluronic acid\n(HA) and decorated with ovalbumin (OVA) as the model antigen. The resulting nanocapsules are\nsmaller than 100 nm, have a negative superficial charge and have a population that is homogeneously\ndistributed. The systems show high colloidal stability in storage and physiological conditions and\nhigh OVA association without losing their integrity. The elevated interaction of the novel formulation\nwith the immune system was demonstrated through complement activation and macrophage viability\nstudies. Ex vivo studies using a pig skin model show the ability of these novel nanocapsules to\npenetrate and retain OVA in higher quantities in skin when compared to this antigen in the control\nsolution. Due to these findings, HA-NCs are an interesting platform for needle-free vaccination.
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