Abstract 130: Immediate Stabilization of Subarachnoid Hemorrhage by Intranasal Delivery of Novel Therapeutics

Abstract

Background: Stroke treatment is a challenge because of the short time window. Intranasal therapeutics delivery is a promising administration options for early delivery of brain stabilization agent as both brain and nasal compartments are interconnected via the olfactory/trigeminal structure and the peripheral circulation. Due to the stabilization effect of nitric oxide (NO) on endothelium, vascular smooth muscle, polymorphonuclear neutrophils (PMNs) in acute cellular and tissue injury, NO releasing agents has been used for emergent cardiovascular conditions such as acute cardiac ischemia and stroke. Here we investigated an intranasal carrier/NO therapeutic delivery strategy to the brain for acute treatment in hemorrhage stroke. Methods: NO/argon (1:9) in caged molecular, cyclodextrin, in liposomal formulation was created to carry NO. A total 200 ul (50 ul per 2 minutes х 4 times) of the NO liposomal formulation or a liposomal carrier control was administrated intranasally at 30 minutes after subarachnoid hemorrhage (SAH). Distribution of NO in brain was imaged with DAF-FM. Hemorrhagic volume was quantified by spectrophotometric hemoglobin assay two hours after SAH. Results: NO distribution was noted in normal brain tissue (Fig.1A). SAH rats had reduced NO distribution due to hemoglobin scavenging of NO (Fig.1B). Intranasal NO liposomal delivery enhanced NO distribution especially in the cerebral microvascular in SAH brain (Fig. 1C). Effective intranasal NO liposomal delivery resulted in decreased hemorrhagic volume (115 ± 22μl) vs SAH without treatment control (344 ± 63μl, p=0.014) as well as SAH with intranasal liposomes control (298 ± 114μl, p=0.02) (Fig. 1D). Conclusions: The Intranasal delivery route of liposomal carriers efficiently delivers therapeutics into the brain. These carriers have controlled release properties in addition to their therapeutic payload effects. The present method has great potential for immediate delivery in stroke.