TOXICOLOGICAL ASPECTS OF THE USE OF DEXTRAN MICROSPHERES AND THERMOGELLING ETHYL(HYDROXYETHYL) CELLULOSE (EHEC) AS NASAL DRUG-DELIVERY SYSTEMS

The impact on the integrity of nasal mucosa and the ciliary beat frequ ency after nasal administration of two formulations enhancing absorpti on of insulin have been evaluated. Dextran microspheres did not influe nce the ciliary beat frequency in vitro but the ethyl(hydroxyethyl) ce llulose (EHEC) system caused irreversible ciliostasis. The hypoosmotic nature of the gel was the major reason for the observed effect. Modes t goblet cell hyperplasia was observed in nasal mucosa after repeated administration of dextran microspheres and thermogelling EHEC. The cha nges observed were located in the anterior part of the nasal cavity. T his area is probably exposed to dehydration by the spheres and prolong ed hypoosmotic conditions by the EHEC system due to the deposition of the delivery systems in the anterior part of nasal cavity. However, bo th dextran microspheres and thermogelling EHEC can be considered as re latively safe vehicles for nasal administration of drugs.