Toxicological investigations of the effects carboxymethylcellulose on ciliary beat frequency of human nasal epithelial cells in primary suspension culture and in vivo on rabbit nasal mucosa

The objective of this study was to investigate the safety of a mucoadhesive carboxymethylcellulose (CMC) formulation for intranasal administration of apomorphine. The effect of different concentrations of CMC on ciliary beat frequency (CBF) was studied using a human nasal epithelial suspension cell culture system. The CBF was determined by computerized microscope photometr y. The in vivo rabbit nasal mucosal tolerance of the mucoadhesive polymer w as investigated using light microscopy. Twice daily, six rabbits received C MC powder in one nostril and CMC/apomorphine powder in the alternate nostri l for 4 weeks. Two control rabbits received air puffs in one nostril and no thing in the alternate nostril il. The rabbits were subsequently sacrificed and the stained nasal sections examined microscopically. CMC showed both c oncentration- and time-dependent inhibitory effects on the CBF. Only mild-t o-moderate cilio-inhibition was recorded with the different concentrations of the polymer. CMC (both with and without apomorphine) caused mild-to-mode rate inflammation after 4 weeks. Necrosis, squamous metaplasia or ciliary d egeneration was not observed. Based on: (1) the mild-to-moderate cilio-inhi bition induced by different concentrations of CMC; and (2) the mild-to-mode rate nasal mucosal inflammation caused by CMC with and without apomorphine, we conclude that this polymer can be considered as a safe carrier for shor t-term intranasal administration. However, further investigations are requi red for its use in the treatment of chronic diseases such as with apomorphi ne in Parkinson's disease. (C) 2000 Elsevier Science B.V. All rights reserv ed.