Nasal toxicological investigations of Carbopol 971P formulation of apomorphine: effects on ciliary beat frequency of human nasal primary cell cultureand in vivo on rabbit nasal mucosa

Objective: The objective of this study was to investigate the nasal toxicit y of a mucoadhesive Carbopol 971P formulation of apomorphine. Materials and methods: The effects of different concentrations of Carbopol 971P and apom orphine on ciliary beat frequency (CBF) were studied in suspension cultures of human nasal epithelial cells. The rabbit nasal mucosal tolerance of the formulation and its components were investigated using light microscopy. D ifferent groups of the rabbits received twice daily, air puffs, glucose, gl ucose/apomorphine, Carbopol 971P or Carbopol 971P/apomorphine for 1 week (g lucose-treated rabbits) or 1, 2 and 4 weeks (other treatments). Results: Bo th Carbopol 971P and apomorphine showed both concentration- and time-depend ent inhibitory effects on the CBF. The effects on CBF were: apomorphine, 1. 0% w/v, irreversible ciliostasis; 0.1 and 0.5% w/v, reversible cilio-inhibi tion; 0.01%w/v, irreversible cilio-stimulation; and Carbopol 971P, 0.1 and 0.25% w/v, partially-reversible cilio-inhibition. Glucose and glucose/apomo rphine physical mixture caused mild inflammation. Carbopol 971P (both with and without apomorphine) caused severe inflammation, which increased with d uration of treatment. Necrosis, squamous metaplasia or ciliary degeneration was not observed. Conclusions: Due to the severe inflammation caused by Ca rbopol 971P with and without apomorphine, we conclude that this polymer is not a suitable carrier for intranasal administration of apomorphine. This i s in spite of the reversible effects of Carbopol 971P (0.1 and 0.25% w/v) a nd apomorphine (0.1 and 0.5% w/v) on CBF. (C) 2000 Published by Elsevier Sc ience BN. All rights reserved.