Nasal Inflammation and Ulceration Secondary to Repeated Use of an Intranasal Delivery Device in Rabbits

Abstract

Intranasal administration of drugs is gaining popularity in medicine, and several animal models have been used to test the safety and efficacy of this delivery route. Nevertheless, the nasal anatomy of animals is different from humans, which can lead to pathological changes that stem from the delivery device and not the drug itself. Here, we report on nasal inflammation and ulceration in rabbits, secondary to the repeated trauma caused by the intranasal device. Similar changes were noted in the animals treated with the vehicle and with the tested drug, and therefore, these changes were not attributed to the drug itself. In some animals, superficial ulcer and stromal inflammation were noted in the eyes, secondary to nasal duct obstruction from the nasal inflammation. These observations emphasize the importance of proper interpretation of histopathological changes, attributed to trauma-induced pathological changes related to the handling of the animal and not to the tested product, which is the drug itself and the device that is optimized for clinical (human) use.

Preclinical In-Vivo Safety of a Novel Thyrotropin-Releasing Hormone-Loaded Biodegradable Nanoparticles After Intranasal Administration in Rats and Primates

“…Local histopathological changes in the nasal application sites have been reported before in other animal models where different nasal application devices were used. These included, for example, inflammation and ulceration, 19 which were attributed to mechanical trauma. Such traumatic effects can also be seen in humans using intranasal sprays, including reports on epistaxis and, rarely, ulceration and septal perforation.…”

“…17 In recent years, there is a growing interest in the intranasal route for drug administration, as a non-invasive way for local, systemic or central nervous system distribution. 18,19 Since intranasal administration can expedite the crossing of the blood-brain barrier of several peptides, 20,21 it has also been suggested as a potential route for TRH administration. 22,23 Nevertheless, when administered in aqueous solution, it is challenging to enable nasal absorption and entrance through the nasal epithelium of the hydrophilic and charged TRH peptide.…”