Sunlight triggered photodynamic ultradeformable liposomes against Leishmania braziliensis are also leishmanicidal in the dark

• Published in: Journal of controlled release 2010-11, Vol.147 (3), p.368-376
• Main Authors: Montanari, Jorge, Maidana, Cristina, Esteva, Mónica Inés, Salomon, Cristina, Morilla, Maria Jose, Romero, Eder L.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Biological and medical sciences; Cercopithecus aethiops; Chemistry, Pharmaceutical; Cutaneous leishmaniasis; Drug Compounding; Female; General pharmacology; Humans; Hydrophobic and Hydrophilic Interactions; Indoles - administration & dosage; Indoles - chemistry; Indoles - metabolism; Indoles - pharmacology; Indoles - toxicity; Leishmania braziliensis; Leishmania braziliensis - drug effects; Leishmaniasis, Cutaneous - drug therapy; Liposomes; Medical sciences; Mice; Microscopy, Confocal; Organometallic Compounds - administration & dosage; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; Organometallic Compounds - pharmacology; Organometallic Compounds - toxicity; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photochemotherapy; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - chemistry; Photosensitizing Agents - metabolism; Photosensitizing Agents - pharmacology; Photosensitizing Agents - toxicity; Skin - metabolism; Skin Absorption; Sunlight; Time Factors; Transcutaneous; Ultradeformable liposomes; Vero Cells
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2010.08.014

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 15 min sunlight irradiation (15 J/cm 2). However, when loaded in UDL as UDL-ZnPc (1.25 μM ZnPc–1 mM 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. Enhanced skin penetration and anti-amastigote activity against Leishmania braziliensis of Zn phthalocyanine (ZnPc) when loaded in ultradeformable liposomes (UDL). [Display omitted]