Pramipexole thermosensitive nasal gel for experimental parkinsonism in rats

Abstract

The nose-to-brain drug delivery theory has been verified by numerous studies. Previously, we also demonstrated improved pharmacokinetics and pharmacodynamics of a selegiline thermosensitive gel in rats. Here, we developed a thermosensitive gel formulation of pramipexole and compared its anti-Parkinsonian effects with those of an orally administered pramipexole solution. The gel formulation containing 16% poloxamer 407 and 0.15% guar gum formed a stiff gel at 32–33 °C and released up to 95% of the drug within 8 h across goat nasal mucosa. Rotenone was administered at 3 mg/kg for 11 days to induce motor deficits, and pramipexole was administered as a post-treatment at 0.3 or 0.6 mg/kg for 10 days. Intranasally administered pramipexole gel effectively recovered locomotor activity scores, abolished catalepsy, increased the levels of brain glutathione and dopamine, and restored catalase activity to normal levels. The formulated pramipexole gel improved motor performance via its dopamine-agonistic activity and countered rotenone-induced oxidative damage to dopaminergic neurons, thereby restoring brain dopamine levels in rats. Intranasally administered low-dose pramipexole could be considered as a first-line therapy for Parkinson's disease.