title: Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Alves
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Iglesias
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Daiana K
authors.initials: DK
authors.lastname: Deda
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Budu
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Tiago A
authors.initials: TA
authors.lastname: Matias
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Vânia B
authors.initials: VB
authors.lastname: Bueno
authors.affiliation: Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo.
authors.forename: Fernando V
authors.initials: FV
authors.lastname: Maluf
authors.affiliation: Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo.
authors.forename: Rafael V C
authors.initials: RV
authors.lastname: Guido
authors.affiliation: Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo.
authors.forename: Glaucius
authors.initials: G
authors.lastname: Oliva
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Luiz H
authors.initials: LH
authors.lastname: Catalani
authors.affiliation: Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo.
authors.forename: Koiti
authors.initials: K
authors.lastname: Araki
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo. Electronic address: cgarcia@usp.br.
authors.forename: Celia R S
authors.initials: CR
authors.lastname: Garcia
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry; D003094:Collagen / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008665:Metalloporphyrins / Q000008:administration & dosage*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D008665:Metalloporphyrins; D053769:Nanocapsules; C059821:atelocollagen; D003094:Collagen
keywords: Malaria; Metalloporphyrins; Nanoparticle encapsulation; Plasmodium falciparum