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Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes

Authors Perez AP, Casasco A, Schilrreff P, Defain Tesoriero MV, Duempelmann L, Altube MJ, Higa L, Morilla MJ, Petray P, Romero EL

Received 12 January 2014

Accepted for publication 20 March 2014

Published 10 July 2014 Volume 2014:9(1) Pages 3335—3345

DOI https://doi.org/10.2147/IJN.S60543

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Ana Paula Perez,1 Agustina Casasco,2 Priscila Schilrreff,1 Maria Victoria Defain Tesoriero,1,3 Luc Duempelmann,1 Maria Julia Altube,1 Leticia Higa,1 Maria Jose Morilla,1 Patricia Petray,2 Eder L Romero1

1Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, 2Servicio de Parasitología y Enfermedad de Chagas, Hospital de Niños Ricardo Gutiérrez, 3Unidad Operativa Sistemas de Liberación Controlada, Centro de Investigación y Desarrollo en Química, Instituto Nacional de Tecnología Industrial (INTI), Buenos Aires, Argentina

Abstract: In this work, the in vitro anti-Leishmania activity of photodynamic liposomes made of soybean phosphatidylcholine, sodium cholate, total polar archaeolipids (TPAs) extracted from the hyperhalophile archaea Halorubrum tebenquichense and the photosensitizer zinc phthalocyanine (ZnPcAL) was compared to that of ultradeformable photodynamic liposomes lacking TPAs (ZnPcUDLs). We found that while ZnPcUDLs and ZnPcALs (130 nm mean diameter and –35 mV zeta potential) were innocuous against promastigotes, a low concentration (0.01 µM ZnPc and 7.6 µM phospholipids) of ZnPcALs irradiated at a very low-energy density (0.2 J/cm2) eliminated L. braziliensis amastigotes from J774 macrophages, without reducing the viability of the host cells. In such conditions, ZnPcALs were harmless for J774 macrophages, HaCaT keratinocytes, and bone marrow-derived dendritic cells. Therefore, topical photodynamic treatment would not likely affect skin-associated lymphoid tissue. ZnPcALs were extensively captured by macrophages, but ZnPcUDLs were not, leading to 2.5-fold increased intracellular delivery of ZnPc than with ZnPcUDLs. Despite mediating low levels of reactive oxygen species, the higher delivery of ZnPc and the multiple (caveolin- and clathrin-dependent plus phagocytic) intracellular pathway followed by ZnPc would have been the reason for the higher antiamastigote activity of ZnPcALs. The leishmanicidal activity of photodynamic liposomal ZnPc was improved by TPA-containing liposomes.

Keywords: macrophages, Leishmania amastigotes, Zn intracellular delivery, irradiation

Corrigendum for this paper has been published

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Enhanced photodynamic leishmanicidal activity of hydrophobic zinc phthalocyanine within archaeolipids containing liposomes [Corrigendum]

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