Figure 11.

Histopathological examination of sections of sheep nasal mucosal membrane. (A) Negative control: hematoxylin and eosin staining of nasal mucosa membrane applied with phosphate buffer reveal unaffected nasal cells with intact basement membranes (red arrows), as well as undamaged glandular cells with clear nuclei (yellow arrow). (B) Positive control: nasal mucosa treated with isopropyl alcohol suffered severe cellular and histological damage. The treatment with isopropyl alcohol disrupted basement membrane (yellow arrow) and loss of nucleus of glandular cells to form a multinucleated cells. (C) Test: nasal in situ gel of darunavir when exposed to nasal tissues of the sheep showed intact basement membrane (red arrow) and normal arrangement of the glandular cells with well-defined nuclei (yellow arrow), indicating no signs of toxicity of the formulation.