Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum

Autor(es):Mostrar menos -

Alves, Eduardo ^{[1, 2]} ; Iglesias, Bernardo A. ^[3] ; Deda, Daiana K. ^[3] ; Budu, Alexandre ^[1] ; Matias, Tiago A. ^[3] ; Bueno, Vania B. ^[3] ; Maluf, Fernando V. ^[4] ; Guido, Rafael V. C. ^[4] ; Oliva, Glaucius ^[4] ; Catalani, Luiz H. ^[3] ; Araki, Koiti ^[3] ; Garcia, Celia R. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Fisiol, Inst Biociencias, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Parasitol, Inst Ciencias Biomed, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ctr Biotecnol Mol Estrutural, Inst Fis Sao Carlos, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Nanomedicine-Nanotechnology Biology and Medicine; v. 11, n. 2, p. 351-358, FEB 2015.
• Citações Web of Science: 8

Resumo

Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro-and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50 = 330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 mu M Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. From the Clinical Editor: In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form. (C) 2015 Published by Elsevier Inc. (AU)

• Processo FAPESP: 11/51295-5 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático