Study on the nasal drug delivery system of PPX microcapsules in situ thermosensitive gel

Pramipexole hydrochloride (PPX) is a dopamine receptor agonist for the treatment of Parkinson's disease. It does not penetrate easily into the brain due to the presence of the blood-brain barrier (BBB), which hinders the treatment of the disease. The nasal mucosal drug delivery system is an effective method to deliver drugs to the brain bypassing the blood-brain barrier and the concentration of drugs targeted to the brain by intranasal administration is quite low due to the limitation of the permeability of the nasal mucosa and the nasal environment. Therefore, this study innovatively encapsulates prepared PPX microcapsules in a temperature-sensitive in situ gel for intranasal drug delivery to increase the target concentration of the drug in the brain and prolong the duration of treatment. The gel formulation containing 24% poloxamer 407 and 6% poloxamer 188 and 0.3% ice chips as absorption enhancers formed a hard gel at 30.44-31.36^oC and allowed a slow release within 12 hours. A pharmacokinetic comparison of the developed PPX microencapsulated temperature-sensitive in situ gel (PPX-MTISG) with PPX temperature-sensitive in situ gel (PPX-TISG) revealed that the microencapsulated nasal mucosal in situ gel was a more effective PPX brain-targeted drug delivery system.