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Nanomedicine. 2015 Feb;11(2):351-8. doi: 10.1016/j.nano.2014.09.018. Epub 2014 Nov 15.

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

Author information

1
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo.
2
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
3
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo.
4
Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo.
5
Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo. Electronic address: cgarcia@usp.br.

Abstract

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 μM 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.

KEYWORDS:

Malaria; Metalloporphyrins; Nanoparticle encapsulation; Plasmodium falciparum

PMID:
25461288
DOI:
10.1016/j.nano.2014.09.018
[Indexed for MEDLINE]

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