title: Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark.
abstract: Being independent of artificial power sources, self administered sunlight triggered photodynamic therapy could be a suitable alternative treatment for cutaneous leishmaniasis, that avoids the need for injectables and the toxic side effects of pentavalent antimonials. In this work we have determined the in vitro leishmanicidal activity of sunlight triggered photodynamic ultradeformable liposomes (UDL). ZnPc is a hydrophobic Zn phthalocyanine that showed 20% anti-promastigote activity (APA) and 20% anti-amastigote activity (AA) against Leishmania braziliensis (strain 2903) after 15min sunlight irradiation (15J/cm(2)). However, when loaded in UDL as UDL-ZnPc (1.25μM ZnPc-1mM phospholipids) it elicited 100% APA and 80% AA at the same light dose. In the absence of host cell toxicity, UDL and UDL-ZnPc also showed non-photodynamic leishmanicidal activity. Confocal laser scanning microscopy of cryosectioned human skin mounted in non-occlusive Saarbrücken Penetration Model, showed that upon transcutaneous administration ZnPc penetrated nearly 10 folds deeper as UDL-ZnPc than if loaded in conventional liposomes (L-ZnPc). Quantitative determination of ZnPc confirmed that UDL-ZnPc penetrated homogeneously in the stratum corneum, carrying 7 folds higher amount of ZnPc 8 folds deeper than L-ZnPc. It is envisioned that the multiple leishmanicidal effects of UDL-ZnPc could play a synergistic role in prophylaxis or therapeutic at early stages of the infection.
authors: Programa de Nanomedicinas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876 BXD, Buenos Aires, Argentina.
authors: Jorge
authors: J
authors: Montanari
authors: Cristina
authors: C
authors: Maidana
authors: Mónica Inés
authors: MI
authors: Esteva
authors: Cristina
authors: C
authors: Salomon
authors: Maria Jose
authors: MJ
authors: Morilla
authors: Eder L
authors: EL
authors: Romero
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D004339:Drug Compounding; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D054833:Isoindoles; D007892:Leishmania braziliensis / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D008081:Liposomes; D051379:Mice; D018613:Microscopy, Confocal; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D010316:Particle Size; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013472:Sunlight; D013997:Time Factors; D014709:Vero Cells; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine