生物技术与生物材料

抽象的

The Use of Intranasal Versus Intravenous Route to Limit Adverse Effects of Amphotericin B Administration

Naveed Ahmed Khan*, Ruqaiyyah Siddiqui, and Timothy Yu Yee Ong

Infection due to Naegleria fowleriis devastating and results in death within days, with more than a 90% mortality rate. The current mode of treatment is via intravenous therapy and is not very effective. For the first time, we tested the modality of the intranasal route to treat this deadly brain infection versus the intravenous route, post-infection in vivo. We compared the adverse effects of Amphotericin B administration, through blood biochemistry, liver, kidney and brain histopathological evidence of toxicities in both scenarios. The findings clearly depicted that intranasal administration of Amphotericin B, in comparison to the intravenous route significantly limited the adverse side effects in vivo. As N. fowleri exhibits unequivocal affinity to the olfactory bulb and frontal lobe in the central nervous system and the fact that parasite portal of entry is via nose, intranasal administration of therapy may be able to directly reach amoebae bypassing the blood-brain barrier selectivity and achieve the minimum inhibitory concentration at the target site. These findings are very encouraging and could lead to the development of a much needed new mode of therapy for this distressing infection. This work is pioneering, and could be a key step in the rationale development of therapeutic interventions against brain-eating amoebae infections by highlighting the use of the intranasal route as a modality to treat this normally fatal infection.