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

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 3335 - 3345
• Main Authors: Perez, Ana Paula, Casasco, Agustina, Schilrreff, Priscila, Tesoriero, Maria Victoria Defain, Duempelmann, Luc, Pappalardo, Juan Sebastián, Altube, Maria Julia, Higa, Leticia, Morilla, Maria Jose, Petray, Patricia, Romero, Eder L
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2014; Dove Press; Dove Medical Press
• Subjects: Animals; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacokinetics; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Archaea; Care and treatment; Cell Line; Cell Survival - drug effects; Glyceryl Ethers - chemistry; Glyceryl Ethers - pharmacokinetics; Glyceryl Ethers - pharmacology; Glyceryl Ethers - toxicity; Halorubrum; Humans; Indoles - chemistry; Indoles - pharmacokinetics; Indoles - pharmacology; Indoles - toxicity; irradiation; Leishmania - drug effects; Leishmania - radiation effects; Leishmania amastigotes; Leishmaniasis; Liposomes; Liposomes - chemistry; Liposomes - pharmacokinetics; Liposomes - pharmacology; Liposomes - toxicity; macrophages; Macrophages - metabolism; Mice; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacokinetics; Organometallic Compounds - pharmacology; Organometallic Compounds - toxicity; Original Research; Phthalocyanins; Properties; Reactive Oxygen Species - analysis; Reactive Oxygen Species - metabolism; Zn intracellular delivery; Argentina; Zn intracellular delivery; macrophages; Leishmania amastigotes; irradiation
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S60543

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/cm(2)) 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.