In vitro evaluation of bisnaphthalimidopropyl derivatives loaded into pegylated nanoparticles against Leishmania infantum protozoa

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Sofia Costa Lima (Author) Other; Vasco Rodrigues (Author) Other; Jorge Garrido (Author) Other; Fernanda Borges (Author) FCUP; Paul Kong Thoo Lin (Author) Other; Anabela Cordeiro da Silva (Author) FFUP

Journal

Title: International Journal of Antimicrobial Agents

Vol. 39

Pages: 424-430

ISSN: 0924-8579

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 22 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Physical sciences > Chemistry > Applied chemistry > Pharmaceutical chemistry

Other information

Authenticus ID: P-002-AWG

DOI: 10.1016/j.ijantimicag.2012.01.003

Abstract (EN): Bisnaphthalimidopropyl (BNIP) derivatives have recently been shown to have potential as antileishmanial agents. However, these compounds have some drawbacks, including their low aqueous solubility and some toxic effects. In this study, we designed a drug delivery system for enhanced delivery of BNIP derivative compounds whilst reducing adverse toxic effects, and hence increasing their biological efficacy. A coated drug delivery system based on polymeric nanoparticles of pegylated poly(lactic acid) (PLA), a biodegradable polymer, was successfully achieved. The pegylated PLA nanoformulations loaded with BNIP derivatives were evaluated in an in vitro model of intracellular amastigotes in murine J774 and human THP-1 cells for visceral leishmaniasis using luciferase-expressing Leishmania infantum parasites. Pegylation of PLA nanoparticles significantly reduced the capacity of empty nanoparticles in inhibiting intracellular parasite growth. The BNIP derivatives BNIPDadec and BNIPDaoct exhibited EC50 values (concentration of compound necessary to decrease cell viability to 50% of the untreated control) of ca. 4.5 mu M for THP-1 and J774 cells and ca. 9.0 mu M for mouse bone marrow-derived macrophages. Nanoparticle encapsulation of the BNIP derivative compounds decreased their toxicity towards macrophages by >= 10-fold as evaluated by the MTT assay. The antileishmanial activity of free BNIPDadec was 1.02 +/- 0.41 mu M and 0.73 +/- 0.06 mu M for THP-1 and J774 macrophages, respectively. Pegylation of PLA nanoparticles loaded with BNIPDadec resulted in EC50 values of 1.43 +/- 0.63 mu M and 1.79 +/- 0.77 mu M for THP-1 and J774 macrophages, respectively. A similar trend was observed for free BNIPDaoct and pegylated BNIPDaoct PLA nanoparticles (2.43 perpendicular to 0.19 mu M and 1.23 perpendicular to 0.40 mu M for THP-1 macrophages and 1.36 +/- 0.17 mu M and 1.52 +/- 0.57 mu M for J774 macrophages). The nanoformulations were more efficient in reducing parasitic growth inside human macrophages than in murine cells, suggesting host cell-dependent metabolism.

Language: English

Type (Professor's evaluation): Scientific