In situ thermosensitive gel of levodopa: Potential formulation for nose to brain delivery in Parkinson disease

Abstract

Parkinson's disease is a disabling neurodegenerative disease which limits many functional activities of the patients. Treatment of the disease by oral formulations is not successful and even applicable in some patients because of difficulty in swallowing. Levodopa is one of the commonly used drugs for Parkinson's disease which bioavailability of its oral formulations is variable between patients. The aim of the present study was to develop an in-situ gel forming formulation for nasal delivery of levodopa. Poloxamer 407, chitosan and alginate were used as thermosensitive and mucoadhesive polymers for formulating nasal gel. Different concentrations of polymers and drug were tested to optimize the gelation temperature. Based on the gelation temperature, two formulations (PL7 and PAL10) which respectively contained poloxamer 20% and levodopa 0.3% w/v and poloxamer 18%, Alginate 0.4% and levodopa 0.3% w/v presented desirable properties for a nasal gel. The gels showed suitable pH, clarity and strength as well as sustained release profile which is necessary for a formulation designed for retention in the nasal cavity. It seems that thermosensitive nasal gel of levodopa with poloxamer could be a potentially successful formulation for delivery of levodopa to the brain.