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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CONTROLLED RELEASE; v. 333, p. 298-315, MAY 10 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 19/02171-3 - Investigação da atividade antimalárica e de alvos moleculares de compostos naturais identificados por quimioinformática contra Plasmodium vivax
• Beneficiário: Letícia Tiburcio Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/18384-8 - Desenvolvimento de patches contendo a associação de artemeter-lumefantrina para o tratamento da malária causada por Plasmodium falciparum
• Beneficiário: Fabiana Volpe Zanutto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 14/16008-3 - Desenvolvimento de patches contendo a associação de artemeter - lumefantrina para o tratamento da malária causada por Plasmodium falciparum
• Beneficiário: Fabiana Volpe Zanutto
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/18611-7 - Desenvolvimento de novas ferramentas para busca e validação de alvos moleculares para terapia contra Plasmodium vivax
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Temático