Study on the Nasal Drug Delivery System of NMD Liposomes In Situ Thermosensitive Gel

Nimodipine (NMD) is a 1,4-dihydropyridine calcium antagonist that is effective in the prevention and treatment of cerebral arterial vasospasm and cerebral ischemic injury caused by subarachnoid hemorrhage. Since the drug itself is highly insoluble in water and has low oral bioavailability, while injectable formulations may cause pain and inflammation, the blood–brain barrier (BBB) prevents the effective delivery of therapeutic agents to the brain tissue. Therefore, in the present study, NMD liposomes were prepared by ethanol injection and innovatively lyophilised and loaded into temperature-sensitive in situ gels for intranasal administration as sprays to deliver drugs to brain tissues bypassing the blood–brain barrier. The optimal gel formulation was obtained by screening in which liposomes were divided into lecithin, cholesterol, and NMD in the ratio of 40:10: 1; Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone and ethyl nipagin in the ratio of (180:20:3:1:1); Pluronic P407, Pluronic P188, Tween 80, polyvinyl ketone, and ethyl nipagin in the ratio of (180:20:3:1:1). The prepared flow gel can form a solidified gel after a temperature of 31.07–32.07°C and a time of 58.51–59.89 s. Meanwhile, the NMD liposome gel formulation achieved sustained release over 56 h. The pharmacokinetic results of the developed NMD liposomal temperature-sensitive in situ gel and NMD temperature-sensitive in situ gel showed that liposomal nasal mucosal in situ gel is a more effective brain-targeted drug delivery system for NMD. Graphical Abstract