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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Artemether and lumefantrine dissolving microneedle patches with improved pharmacokinetic performance and antimalarial efficacy in mice infected with Plasmodium yoelii

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Volpe-Zanutto, Fabiana [1, 2, 3] ; Ferreira, Leticia Tiburcio [4] ; Permana, Andi Dian [2, 5] ; Kirkby, Melissa [2] ; Paredes, Alejandro J. [2] ; Vora, Lalitkumar K. [2] ; Bonfanti, Amanda P. [3, 6] ; Charlie-Silva, Ives [7] ; Raposo, Catarina [3] ; Figueiredo, Mariana C. [3] ; Sousa, Ilza M. O. [3] ; Brisibe, Andi [8] ; Costa, Fabio Trindade Maranhao [4] ; Donnelly, Ryan F. [2] ; Foglio, Mary Ann [3]
Total Authors: 15
Affiliation:
[1] Univ Estadual Campinas, Grad Sch Biosci & Technol Bioact Prod, Biol Inst, R Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil
[2] Queens Univ Belfast, Med Biol Ctr, Sch Pharm, 97 Lisburn Rd, Belfast BT9 7BL, Antrim - North Ireland
[3] Univ Estadual Campinas, Fac Pharmaceut Sci, R Candido Portinari 200, BR-13083871 Campinas, SP - Brazil
[4] Univ Estadual Campinas, Lab Trop Dis Prof Dr Luiz Jacintho da Silva, Dept Genet Evolut Microbiol & Immunol, Inst Biol, R Carl von Linaeus 2-238, BR-13083864 Campinas, SP - Brazil
[5] Hasanuddin Univ, Fac Pharm, Dept Pharmaceut, Makassar 90245 - Indonesia
[6] Univ Estadual Campinas, Biol Inst, Dept Funt & Struct Biol, R Monteiro Lobato 255, BR-13083862 Campinas, SP - Brazil
[7] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, SP - Brazil
[8] Univ Calabar, Calabar - Nigeria
Total Affiliations: 8
Document type: Journal article
Source: JOURNAL OF CONTROLLED RELEASE; v. 333, p. 298-315, MAY 10 2021.
Web of Science Citations: 1
Abstract

Malaria affects more than 200 million people annually around the world, killing a child every 2 min. Artemether (ART) and lumefantrine (LUM) are the gold standard choice to treat uncomplicated Plasmodium falciparum malaria; however, they are hydrophobic compounds with low oral bioavailability. Microneedle (MN) arrays consist of micron-sized needles on one side of a supporting base and have the ability to bypass the skin's stratum corneum barrier in a minimally invasive way, creating temporary channels through which drugs can diffuse, including those with poor water solubility. Herein, we report the development of dissolving MNs (DMNs) containing ART (MN-ART) and LUM (MN-LUM) as an alternative treatment regimen for malaria in low-resource settings. To incorporate the drugs into the MNs, nanosuspensions (NSs) for both molecules were developed separately to enhance drug solubility. The NSs were freeze-dried and the powder form was incorporated directly in an aqueous polymeric blend with poly-vinyl-pyrrolidone for MN-ART and a sodium hyaluronate hydrogel for MN-LUM. The in vivo bioavailability studies were performed using a MN reapplication scheme (1 x a day for 3 days), illustrating that an extended-release profile was achieved for both drugs when MNs were applied intradermally, and when compared to conventional oral treatment. The ART-LUM oral treatment was used as a positive control. For antimalarial activity, studies with animals infected with 106 Plasmodium yoelii 17XNL (12 days) were also conducted using female C57BL/6JUnib mice, demonstrating a 99.5% reduction in parasitemia by day 12 post-infection. By abolishing the infection, MN-ART and MN-LUM may serve as a promising controlled intradermal delivery device for antimalarial drugs to be explored in endemic areas. (AU)

FAPESP's process: 19/02171-3 - Investigation of antimalarial activity and molecular targets of natural compounds identified by chemoinformatics against Plasmodium vivax
Grantee:Letícia Tiburcio Ferreira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 16/18384-8 - Development of patches containing the association of artemether-lumefantrine for the treatment of malaria caused by Plasmodium falciparum
Grantee:Fabiana Volpe Zanutto
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 14/16008-3 - Development of patches containing the association of artemether - lumefantrine for the treatment of malaria caused by Plasmodium falciparum
Grantee:Fabiana Volpe Zanutto
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax
Grantee:Fabio Trindade Maranhão Costa
Support Opportunities: Research Projects - Thematic Grants