Preparation of ergoloid mesylate submicron emulsions for enhancing nasal absorption and reducing nasal ciliotoxicity.

The aim of this investigation was to prepare ergoloid mesylate submicron emulsions (EMSEs) for enhancing nasal absorption of drug and reducing nasal ciliotoxicity. Following intranasal administrations of EMSE and ergoloid mesylate solution (EMS) and intravenous administration of EMS to rats separately at the dose of 2 mg kg(-1), the levels of EM in blood and the cerebrospinal fluid (CSF) were evaluated by microdialysis method. The nasal ciliotoxicity was evaluated by using in situ toad palate model. The absolute bioavailability and the AUC in the CSF following intranasal administration of EMSE (56.3 +/- 5.3%, AUC(CSF) 28,594 +/- 5680 ng ml(-1) min) were statistically higher than those after intranasal administration of EMS (47.4 +/- 3.5%, AUC(CSF) 19,870 +/- 2247 ng ml(-1) min). No significant difference was found for the value of the brain drug direct transport percentage (DTP%) or the drug targeting efficiency (DTE) between the group receiving EMSE and the group receiving EMS. In conclusion, EMSE exhibited higher nasal absorption of EM in rats and significantly lower nasal ciliotoxicity whereas no greater brain-targeting efficiency in comparison with EMS.