Efficacy of intranasal administration of artesunate in experimental cerebral malaria

Malaria Journal

Research

Marie-Claude Gagnieu¹  Anthony Fourier¹  Guillaume Bonnot²  Coralie Bringer²  Adeline Lavoignat²  Anne Marijon³  Anne-Lise Bienvenu³  Stéphane Picot³ 

[1] Hospices Civils de Lyon, Laboratoire de Pharmacologie spécialisée, Hôpital Edouard Herriot, cedex 03, 5 place d’Arsonval, 69437, Lyon, France;Université Claude Bernard Lyon 1, Malaria Research Unit, SMITH, ICBMS, UMR 5246 CNRS-INSA-CPE-UCBL1, cedex 08, 8 avenue Rockefeller, 69373, Lyon, France;Université Claude Bernard Lyon 1, Malaria Research Unit, SMITH, ICBMS, UMR 5246 CNRS-INSA-CPE-UCBL1, cedex 08, 8 avenue Rockefeller, 69373, Lyon, France;Hospices Civils de Lyon, Institut de Parasitologie et de Mycologie Médicale (IP2M), Hôpital de la Croix-Rousse, cedex 04, 103 grande rue de la Croix-Rousse, 69317, Lyon, France;

关键词: Cerebral malaria;    Artesunate;    Intranasal administration;    Pharmacokinetic;    Toxicity;   

DOI  :  10.1186/1475-2875-13-501

 received in 2014-11-17, accepted in 2014-12-12,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundImproving management of patients suffering from cerebral malaria is needed to reduce the devastating mortality and morbidity of the disease in endemic areas. Intravenous artesunate is currently the first-line treatment, but the lack of material and skills in the field make it difficult to implement in endemic areas. Intranasal route provides a very easy and direct gateway to blood and brain to deliver medications, by-passing the brain blood barrier. Therefore, it could be helpful and suitable to administer artesunate in the context of cerebral malaria, especially in young children. In this study, intranasal administration of artesunate to rescue from cerebral malaria using a murine model was tested.MethodsCBA/J mice infected with Plasmodium berghei ANKA strain received artesunate (20 mg/kg) or a placebo solution intranasally, either on day 5, 6 or 7 post-infection, during a controlled, blinded, randomized trial. Primary endpoint was mortality on day 12 post-infection. Secondary endpoints were parasitaemia and clinical stage. Pharmacokinetics data following administration were collected in blood and brains of treated mice. Local toxicity was evaluated by histopathologic examination of brain and nasal sections in blinded manner.ResultsIntranasal administration of artesunate dramatically reduced the mortality rate (p < 0.001), preventing death in most cases. Parasitaemia loads decreased by 88.7% (61.8-100%) within 24 hours after administration. Symptoms of cerebral malaria were prevented or reversed. Dihydroartemisinin was detected in mice blood and brain within 15 minutes of intranasal administration. No direct nasal or brain toxicity was detected.ConclusionIntranasal delivery is an efficient route to timely and efficiently administer artesunate and therefore may contribute to decreasing malaria-related mortality.

【 授权许可】

Unknown   
© Marijon et al.; licensee BioMed Central. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.