Intranasal artesunate-loaded nanostructured lipid carriers : A convenient alternative to parenteral formulations for the treatment of severe and cerebral malaria
Copyright © 2021 Elsevier B.V. All rights reserved..
Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with Plasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:334 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 334(2021) vom: 10. Juni, Seite 224-236 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Agbo, Chinazom Precious [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.07.2021 Date Revised 07.07.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2021.04.020 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324478720 |
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| 100 | 1 | |a Agbo, Chinazom Precious |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intranasal artesunate-loaded nanostructured lipid carriers |b A convenient alternative to parenteral formulations for the treatment of severe and cerebral malaria |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 Elsevier B.V. All rights reserved. | ||
| 520 | |a Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment. Hence, we designed ATS-loaded nanostructured lipid carriers (NLCs) for intranasal administration. ATS-NLCs were formulated using varying concentrations of lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising a 1:2 ratio of Phospholipon ® 90H and lipids (Softisan ® 154 or Compritol ®). ATS-NLCs were spherical, and the small sizes of ATS-NLCs obtained for some formulations (76.56 ± 1.04 nm) is an indication that ATS-NLCs can pass through the nasal mucosa and reach the brain or systemic circulation. Encapsulation efficiency of ATS in NLCs was ≥70% for all formulations. ATS-NLCs achieved up to 40% in vitro drug release in 1 h, while ex vivo permeation studies revealed that formulating ATS as NLCs enhanced permeation through pig nasal mucosa better than drug solution. Most importantly, the activity and reduction in parasitaemia [in mice infected with Plasmodium berghei ANKA in a murine cerebral malaria model] by ATS-NLCs administered through the INR (54.70%, 33.28%) was comparable to intramuscular administration (58.80%, 42.18%), respectively. Therefore, intranasal administration of NLCs of ATS has great potentials to serve as a satisfactory alternative to parenteral administration for the treatment of severe and cerebral malaria in both adults and children in remote areas of sub-Saharan Africa | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Artesunate | |
| 650 | 4 | |a Cerebral malaria | |
| 650 | 4 | |a Intranasal route | |
| 650 | 4 | |a Nanostructured lipid carriers | |
| 650 | 4 | |a Severe malaria | |
| 650 | 4 | |a Solidified reverse micellar solutions | |
| 650 | 7 | |a Drug Carriers |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a Artesunate |2 NLM | |
| 650 | 7 | |a 60W3249T9M |2 NLM | |
| 700 | 1 | |a Ugwuanyi, Timothy Chukwuebuka |e verfasserin |4 aut | |
| 700 | 1 | |a Ugwuoke, Wilfred Ikechukwu |e verfasserin |4 aut | |
| 700 | 1 | |a McConville, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Attama, Anthony Amaechi |e verfasserin |4 aut | |
| 700 | 1 | |a Ofokansi, Kenneth Chibuzor |e verfasserin |4 aut | |
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| 773 | 1 | 8 | |g volume:334 |g year:2021 |g day:10 |g month:06 |g pages:224-236 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jconrel.2021.04.020 |3 Volltext |
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