title: Development and evaluation of zinc phthalocyanine nanoemulsions for use in photodynamic therapy for Leishmania spp.
abstract: Photodynamic therapy (PDT) combines light with photosensitizers (PS) for production of reactive oxygen species (ROS) that can kill infectious microorganisms such as bacteria, fungi and protozoa. The application of nanotechnology has enabled the advancement of PDT because many PS are insoluble in water, necessitating a nanocarrier as a physiologically acceptable carrier. Nanoemulsions are efficient nanocarriers for solubilizing liposoluble drugs, like the PS, in water. Cutaneous (CL) and mucocutaneous leishmaniasis (ML) are caused by different species of the genus Leishmania, transmitted to humans by sandfly bites. Parasites are hosted in skin macrophages producing ulcerative lesions. Thus, a topical treatment, effective and inexpensive, for CL and ML is preferable to systemic interventions. There are topical treatments like paromomycin and amphotericin B, but they have many local side effects or a very high cost, limiting their use. This work aimed to develop a zinc phthalocyanine (photosensitizer) oil-in-water nanoemulsion, essential clove oil and polymeric surfactant (Pluronic®F127) for the formulation of a topical delivery system for use in PDT against Leishmania amazonensis and Leishmania infantum. The nanoemulsion was produced by a high-energy method and characterized by size, polydispersity, morphology, pH, content and stability studies. The toxicity in the dark and the photobiological activity of the formulations were evaluated in vitro for Leishmania and macrophages. The formulation presented was pH compatible with topical use, approximately 30 nm in size, with a polydispersity index ≤0.1 and remained stable at room and refrigerator temperature during the stability study (60 days). The zinc phthalocyanine nanoemulsion is effective in PDT against Leishmania spp.; use against skin infections can be a future application of this topical formulation, avoiding the use of oral or injectable medications, decreasing systemic adverse effects.
authors.affiliation: Laboratório de Desenvolvimento Galênico (LADEG), Departamento de Medicamentos, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Luciana Betzler
authors.initials: LB
authors.lastname: de Oliveira de Siqueira
authors.forename: Verônica
authors.initials: V
authors.lastname: da Silva Cardoso
authors.forename: Igor Almeida
authors.initials: IA
authors.lastname: Rodrigues
authors.forename: Ana Lúcia
authors.initials: AL
authors.lastname: Vazquez-Villa
authors.forename: Elisabete Pereira
authors.initials: EP
authors.lastname: Dos Santos
authors.forename: Bruno
authors.initials: B
authors.lastname: da Costa Leal Ribeiro Guimarães
authors.forename: Cristal
authors.initials: C
authors.lastname: Dos Santos Cerqueira Coutinho
authors.forename: Alane Beatriz
authors.initials: AB
authors.lastname: Vermelho
authors.forename: Eduardo Ricci
authors.initials: ER
authors.lastname: Junior
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D045783:Clove Oil / Q000737:chemistry; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D018314:Leishmania infantum / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development / Q000528:radiation effects; D008027:Light; D051379:Mice; D008826:Microbial Sensitivity Tests; D049329:Nanostructures / Q000737:chemistry; D009569:Nitric Oxide; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D020442:Poloxamer / Q000737:chemistry; D000067996:RAW 264.7 Cells; D017967:Zinc Compounds
chemical_list: D045783:Clove Oil; D004337:Drug Carriers; D004655:Emulsions; D007211:Indoles; D054833:Isoindoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; D020442:Poloxamer; C052159:Zn(II)-phthalocyanine; D009569:Nitric Oxide