Pre-referral intranasal artesunate powder for cerebral malaria: a proof-of-concept study.
Artesunate
Nasal cast
Nasal mucosa
Nose-to-brain delivery
Pre-referral treatment
Severe malaria
Journal
Malaria journal
ISSN: 1475-2875
Titre abrégé: Malar J
Pays: England
ID NLM: 101139802
Informations de publication
Date de publication:
11 Oct 2022
11 Oct 2022
Historique:
received:
11
04
2022
accepted:
02
10
2022
entrez:
11
10
2022
pubmed:
12
10
2022
medline:
14
10
2022
Statut:
epublish
Résumé
Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment. The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry. The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively. Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.
Sections du résumé
BACKGROUND
BACKGROUND
Malaria still kills young children in rural endemic areas because early treatment is not available. Thus, the World Health Organization recommends the administration of artesunate suppositories as pre-referral treatment before transportation to the hospital in case of severe symptoms with an unavailable parenteral and oral treatment. However, negative cultural perception of the rectal route, and limited access to artesunate suppositories, could limit the use of artesunate suppositories. There is, therefore, a need for an alternative route for malaria pre-referral treatment. The aim of this study was to assess the potential of intranasal route for malaria pre-referral treatment.
METHODS
METHODS
The permeability of artesunate through human nasal mucosa was tested in vitro. The Transepithelial Electrical Resistance (TEER) of the nasal mucosa was followed during the permeation tests. Beside, regional deposition of artesunate powder was assessed with an unidose drug delivery device in each nostril of a nasal cast. Artesunate quantification was performed using Liquid Chromatography coupled to tandem Mass Spectrometry.
RESULTS
RESULTS
The experimental model of human nasal mucosa was successfully implemented. Using this model, artesunate powder showed a much better passage rate through human nasal mucosa than solution (26.8 ± 6.6% versus 2.1 ± 0.3%). More than half (62.3%) of the artesunate dose sprayed in the nostrils of the nasal cast was recovered in the olfactory areas (44.7 ± 8.6%) and turbinates (17.6 ± 3.3%) allowing nose-to-brain and systemic drug diffusion, respectively.
CONCLUSION
CONCLUSIONS
Artesunate powder showed a good permeation efficiency on human nasal mucosa. Moreover it can be efficiently sprayed in the nostrils using unidose device to reach the olfactory area leading to a fast nose-to-brain delivery as well as a systemic effect. Taken together, those results are part of the proof-of-concept for the use of intranasal artesunate as a malaria pre-referral treatment.
Identifiants
pubmed: 36221071
doi: 10.1186/s12936-022-04309-0
pii: 10.1186/s12936-022-04309-0
pmc: PMC9555123
doi:
Substances chimiques
Antimalarials
0
Artemisinins
0
Powders
0
Suppositories
0
Artesunate
60W3249T9M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
291Subventions
Organisme : Internship Hospices Civils de Lyon
ID : 2017-2021
Organisme : Annual Grant from University Lyon & CNRS
ID : 2017-2022
Organisme : Annual Grant from University Lyon & CNRS
ID : 2017-2022
Organisme : Annual Grant from University Lyon & CNRS
ID : 2017-2022
Organisme : EDCTP II- WANECAM 2
ID : RIA2017T-2018
Organisme : EDCTP II- WANECAM 2
ID : RIA2017T-2018
Organisme : MORA scholarship, Republic of Indonesia
ID : 2815/DJ.I/DT.I.III/PP.04/07/2018
Informations de copyright
© 2022. The Author(s).
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