Niosomes for nose-to-brain delivery of bromocriptine: Formulation development, efficacy evaluation and toxicity profiling

The present study aimed to formulate stable non-ionic surfactant vesicles incorporating Bromocriptine Mesylate (BCM) to enhance brain uptake via the direct nose to brain pathway. The optimized formulation prepared by ethanol injection method exhibited a size of 180 +/- 4.5 nm, % encapsulation of 75.8 +/- 3.6 and zeta potential of -14.2 +/- 1.8 mV. Ex vivo study demonstrated 6.4 times enhancement in permeation across goat nasal mucosa at 24 h as compared to BCM drug suspension. The relative brain bioavailability, drug targeting efficiency and direct transport percentage of intranasal (i.n) niosomes was found to be 1045.51%, 1118.10% and 91.06% respectively, suggesting enhanced CNS targeting via the direct olfactory pathway. Group treated with BCM niosomes i.n revealed a marked attenuation of cataleptic time along with reduced lipid oxidation and restored Glutathione (GSH) levels in the brain. Sub-acute toxicity studies carried out for 28 days revealed no mortality or toxicologically significant changes. The combination of above results proved that BCM niosomes were safe to be administered i.n displaying manifold enhancement in brain distribution and improved pharmacodynamic be-havior with 10 times dose reduction. Thus, such a system could be positively exploited as an alternative to oral delivery in the management of Parkinson's Disease (PD).