Toxicological evaluation of a bioadhesive nasal powder containing a starch and Carbopol 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 974 P (90/10) on the nasal mucosa of rabbits and the foot mucosa of slugs after multiple administrations. In the rabbit, the effect of the formulation was measured by the release of proteins and lactate dehydrogenase (LDH) from the nasal mucosa with a new non-invasive in vivo method and also by histopathology. The mucosal toxicity of the formulation was evaluated 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 hours 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 additional 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 974 P (90:10, w/w) on the mucosa was negligible.
Callens
C
C
Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Ghent, Harelbekestraat 72, B-9000, Gent, Belgium.
Adriaens
E
E
Dierckens
K
K
Remon
J P
JP
D000179:Acrylates / Q000008:administration & dosage / Q000633:toxicity*; D000281:Administration, Intranasal; D000818:Animals; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009092:Mucous Membrane / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects* / Q000473:pathology; D011208:Powders; D011817:Rabbits; D013213:Starch / Q000008:administration & dosage / Q000633:toxicity*
D000179:Acrylates; D011208:Powders; C117167:carbopol 974P NF; D013213:Starch; D007770:L-Lactate Dehydrogenase