Efficiency of olfactory transport of manganese (II) oxide nanoparticles with single or multiple intranasal administration

Abstract

In experiments in which nano-sized metal oxide particles are multiply administered through inhalation, the absence of a material correlation between the number of they are administered and the metal concentration in olfactory bulbs (OBs) is demonstrated. This circumstance raises the question about a possible decrease in the efficiency of the capture of solid particles by the olfactory epithelium when they are repeatedly introduced in the nasal cavity. In this work, the efficiency of the nasal transport of magneto-contrasting nanoparticles during single and multiple intranasal administration is compared and their effect on the morphofunctional characteristics of the olfactory system is estimated. According to the data obtained, the accumulation of MnO-NP in the OBs of mice decreases during their repeated intranasal application. In addition, the decrease in the efficiency of the olfactory transport (observed during the multiple introduction of MnONP) partially recovers during the intranasal application of a mucolytic agent (0.01 M N-acetyl-L-cysteine). Moreover, the concentration of particles in OBs was proportional to the volume of this structure, which particularly depends on the number of synaptic contacts between the OBs and the olfactory epithelium. It should be noted that the olfactory epithelium’s thickness decreases during the multiple introduction of MnO-NP in mice. Thus, the efficiency of the olfactory transport of nanoparticles from the nasal cavity to the brain decreases during the multiple intranasal introduction of MnO-NP; this is combined with an increase in the mucosal layer’s viscosity and a decrease in the number of synaptic contacts between the OBs and the olfactory epithelium. The results obtained indicate the presence of the natural protection mechanisms of the olfactory epithelium against the penetration of pathogens and xenobiotics and allows us to formulate specific practical recommendations concerning the intranasal application of medications.