Novel O/W nanoemulsions for nasal administration: Structural hints in the selection of performing vehicles with enhanced mucopenetration.

We propose novel oil-in-water nanoemulsions (O/W NEs) including PEGylated surfactants and chitosan, showing good biocompatibility and optimization for nasal administration of drugs or vaccines. The transmucosal route has been shown to be ideal for a fast and efficient absorption and represents a viable alternative when the oral administration is problematic. The critical structural features in view of optimal encapsulation and transmucosal delivery were assessed by characterizing the NEs with complementary scattering techniques, i.e. dynamic light scattering (DLS), small angle X-ray (SAXS) and neutron scattering (SANS). Combined results allowed for selecting the formulations with the best suited structural properties and in addition establishing their propensity to enter the mucus barrier. To this scope, mucin was used as a model system and the effect of adding chitosan to the NEs, as adjuvant, was investigated. Remarkably, the presence of chitosan had a positive impact on the diffusion of the NE particles through the mucin matrix. We can infer that chitosan-mucin interaction induces density inhomogeneity and an increase in the pore size within the gel matrix that enhances the PEGylated NEs mobility. The coupling of mucoadhesive and mucopenetrating agents is shown to be a promising strategy for innovative transmucosal delivery systems.