Intranasal lipid nanocapsules for systemic delivery of nimodipine into the brain: In vitro optimization and in vivo pharmacokinetic study.

Nimodipine (NM) is FDA-approved drug for treating subarachnoid haemorrhage induced vasospasm. Intravenous (IV) administration, the most common route of NM, causes several side effects such as hypotension, bradycardia, arrhythmias and inflammation at site of administration. The aim of this study was to investigate the capability of intranasal (IN) lipid nanocapsules (LNCs) for effective delivery of NM into the brain. NM LNCs were prepared by solvent free phase inversion temperature technique using D-Optimal mixture design studying the effects of three formulation variables on the properties of the prepared LNCs. The prepared particles were evaluated for particle size, drug payload, PDI, Zeta potential and in-vitro drug release. The optimized NM loaded LNC showed particle size of 35.94 ± 0.14 nm and PDI of 0.146 ± 0.045. The in-vivo pharmacokinetic behaviour of IN NM loaded LNC in blood and brain was compared with NM-solution after IV administration in rats. Results show that IN NM loaded LNC was capable to deliver the same amount of NM at brain tissue with lower drug levels in blood compared with IV administration of the NM solution which is greatly beneficial to minimize the cardiovascular side effects of NM. Contrary to most IN nanocarriers, systemic pathway rather than olfactory pathway plays the major role in brain delivery following IN administration of LNCs. The appropriate brain delivery with lower blood levels and slow elimination propose that intranasal LNCs could provide effective systemic delivery of NM into brain with lower frequency of administration and minimal side effects.