Toxicological evaluation of a bioadhesive nasal powder containing a starchand Carbopol (R) 974 P on rabbit nasal mucosa and slug mucosa

The purpose of this study is the investigation of possible adverse effects of a powder formulation containing drum-dried waxy maize (DDWM) starch and Carbopol(R) 974 P (90/10) on the nasal mucosa of rabbits and the foot mucos a of slugs after multiple administrations. In the rabbit, the effect of the formulation was measured by the release of proteins and lactate dehydrogen ase (LDH) from the nasal mucosa with a new non-invasive in vivo method and also by histopathology. The mucosal toxicity of the formulation was evaluat ed using slugs by measuring the effect on the body weight and the amount of mucus produced during a repeated contact period. Additionally, the release of proteins, lactate dehydrogenase and alkaline phosphatase from the body wall of the slugs after a repeated treatment was measured. Twenty four hour s after the powder administration to the rabbits the release of the marker molecules was comparable with the negative controls. The histopathological study showed only a slight increase of granulocytes in the epithelium. The formulation induced a higher mucus production in the slugs but no additiona l effects were detected on the body weight and on the release of proteins. No enzymes were released from the body wall. The results indicate that the effect of the bioadhesive powder consisting of DDWM/Carbopol(R) 974 P (90:1 0, w/w) on the mucosa was negligible. (C) 2001 Elsevier Science B.V. All ri ghts reserved.