CNSC-62. INTRANASAL NOVEL COMPOUND NEO100-FACILITATED STEROID DELIVERY IN MANAGING PERITUMORAL EDEMA IN RAT GLIOMA ANIMAL MODEL

Abstract BACKGROUND Glioma-related edema is a significant indicator of tumor spread1. Extensive edema indicates that the glioma has invaded surrounding healthy brain tissue2. Corticosteroids have been widely used and shown to be particularly beneficial for reducing tumor-associated edema in brain cancer patients. However, when taken orally, corticosteroids are absorbed from the gastrointestinal tract and cleared by the liver. Due to rapid first-pass metabolism, corticosteroids have a short duration of action. Chronic exposure to high levels of circulating exogenous glucocorticoids elevates cortisol levels in the blood and leads to Cushing syndrome, which is linked to significant morbidity and poor health-related quality of life. The development of new therapies to treat cerebral edema is urgently needed. We hypothesize that the adverse effects of high-dose corticosteroids could be mitigated by replacing the conventional oral delivery method with an intranasal application. Innovation: NEO100 is a newly FDA-approved compound for intranasal administration (IN) in Phase IIa clinical trials for recurrent grade III and IV astrocytomas with IDH1 mutations. IN NEO100 has demonstrated great potential for nasal-brain penetration. METHODS The pharmacokinetic (pK) study was performed to compare the efficacy of oral and IN Dexamethasone (Dex) with and without NEO100. Peritumoral cerebral edema was established by injecting F98 rat glioma cancer cells intracranially and treated with either oral Dex, IN Dex, or IN NEO100 + Dex. The edema was monitored and evaluated using 7T MRI. RESULTS The pK study demonstrated that IN NEO100-mediated Dex delivery has better penetration into the plasma and tumor. IN and IN NEO100-mediated Dex delivery can dramatically decrease peritumoral edema compared to oral Dex. CONCLUSION IN NEO100-mediated Dex delivery shows great promise compared to oral administration and is also effective in managing peritumoral edema. Other effects on animal survival, blood sugar levels, liver function, metabolite rates, as well as T3/T4 levels, are under investigation.