Nanospanlastic in situ Gel for Nose to Brain Delivery of Nimodipine: In vitro Optimization and in vivo Pharmacokinetic Study

Background: The FDA has approved the medication nimodipine (NMD) to treat vasospasm brought on by subarachnoid hemorrhage. The most popular way to administer NMD is intravenously, which can result in several adverse effects, including bradycardia, hypotension, arrhythmias, and inflammation at the administration site. Objective: To evaluate the effectiveness of nose-to-brain (NTB) delivery of NMD as spanlastic nanovesicles (SNV) in situ gel into the brain and compare it with IV infusion. Methods: The nanovesicle formulation by the ethanol injection method used Span 60 as a non-ionic surfactant and Tween 60 as an edge activator for enhanced permeability. The nanovesicle formulation is within the accepted range for nose-to-brain mixing with poloxamer 407 to in situ gel formulation by the cold method. Results: The result was observed in the optimized formula with a particle size of 73.18 nm, a PDI of 0.1646, and higher drug entrapment within the vesicles. The in situ gel with the optimized formula shows gelation temperature with nasal fluid temperature. The in vivo pharmacokinetic behavior of NTB in the optimized formula in blood and brain was contrasted with commercial NMD. In contrast to intravenous administration of the NMD, the results indicate that NTB of NMD in situ gel was able to deliver the same amount of NMD to brain tissue with lower drug levels in blood. Conclusions: The nose-to-brain approach for NMD-SNV may be able to deliver NMD systemically to the brain with less frequent dosing and fewer cardiac adverse effects.