Nose to brain delivery of eletriptan hydrobromide nanoparticles: Preparation, in vitro/in vivo evaluation and effect on trigeminal activation

Migraine is a chronic disorder of the brain and acts through peripheral trigeminal activation. Thus, both central and peripheral stimulations can play a part in sensitization and activation of trigeminal neurons. Intranasal drug delivery offers a possible solution due to direct link to trigeminal nerves. A wide variety of therapeutic compounds can be administered intranasally for their topical, systemic and central nervous system (CNS) action. In this study, eletriptan hydrobmmide (EH) loaded PLGA nanoparticles were prepared and their antimigraine activity was evaluated after intranasal administration. It was shown that PLGA nanoparticles had an average particle size of 201.5 +/- 13.6 nm and zeta potential value of - 17.3 +/- 2.11 mV. After cellular uptake and P-glycoprotein efflux studies, EH nanoparticles were shown to overcome P-glycoprotein mediated drug efflux. The pharmacokinetic parameters revealed a marked improvement in the CNS permeation behavior of intranasal EH loaded nanoparticle administration as compared to intravenous administration of drug (p < 0.05). There was two times higher AUC(b)(ra)(in) representing a higher total amount of drug reaching to the brain (AUC(0-infinity) = 100.34 +/- 29.13 ng/ml.h for intranasal nanoparticle administration and AUC(0-infinity) = 60.01 +/- 11.30 ng/ml.h for intravenous solution). We showed that expressions of c-fos and substance P are dependent on the drug that reached to the brain and intranasal drug administration prolonged the expression of substance P and c-fos mRNA levels. Based on the results, intranasal PLGA nanoparticle administration of EH may be evaluated as a better treatment option for migraine therapy.