Jefferson Bruno Pereira Ribeiro1, Ana Luisa Miranda-Vilela2, Daniel Graziani1, Misléia Rodrigues de Aguiar Gomes3, Ana Angélica Santarem Amorim1, Rafaela Debastiani Garcia1, José de Souza Filho4, Antônio Cláudio Tedesco5, Fernando Lucas Primo5, Jonathan Rosa Moreira6, Alexandre Vasconcelos Lima7, Raimunda Nonata Ribeiro Sampaio1. 1. Faculdade de Medicina, Laboratório de Dermatomicologia, Universidade de Brasília, Campus Universitário Darcy Ribeiro, 70910-900 Brasília/DF, Brazil. 2. Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Campus Darcy Ribeiro, 70910-900 Brasília/DF, Brazil; Faculdades Integradas da União Educacional do Planalto Central (Faciplac), Curso de Medicina, Campus Gama, 72460-000 Gama/DF, Brazil. Electronic address: analuisamv@uol.com.br. 3. Faculdade de Medicina, Laboratório Farmacognosia, Universidade de Brasília, Campus Darcy Ribeiro, 70910-900 Brasília/DF, Brazil. 4. Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, Campus Darcy Ribeiro, 70910-900 Brasília/DF, Brazil. 5. Departamento de Química, Laboratório de Fotobiologia e Fotomedicina, Centro de Nanotecnologia e Engenharia Tecidual, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto-SP, Brazil. 6. Faculdades Projeção, Núcleo de Desenvolvimento Científico (NDC), 72115-700 Taguatinga/DF, Brazil. 7. Instituto Brasileiro de Segurança no Trânsito, SRTVS Quadra 701 Bloco 3, Cobertura, Edificio Palácio do Rádio I, Asa Sul, 70340-901 Brasília/DF, Brazil.
Abstract
BACKGROUND: The shortage of drugs is a concern and has become the object of studies to discover effective alternatives for cutaneous leishmaniasis (CL) treatment. A topical formulation has been sought due to its low toxicity. Development of alternative therapies, such as multimodal ones, is important in confronting drug resistance. This study aims to compare the in vivo efficacy of topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of CL, isolated and associated with systemic therapy with miltefosine. METHODS: Five groups were adopted, each one with six isogenic adult female mice C57BL/6: (1) Negative Control-non-infected and non-treated; (2) Positive Control (PBS)-infected and non-treated; (3) Miltefosine-infected and treated with oral miltefosine 200 mg/kg/day; (4) Infected and treated with PDT with topical AlClPC (500 μL) on alternate days; (5) Oral Miltefosine 200 mg/kg/day and PDT with topical AlClPC (500 μL) on alternate days. Therapeutic schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle medium (NNN) of lymph collected from the animal paw, and animals were evaluated by paw measurement and parasitological criteria. RESULTS: Miltefosine associated with PDT with AlClPC promoted a significant reduction in parasite number and viability when compared to the other infected groups, also returning the paw diameter to a size similar to the negative control group after 20 days of treatment. CONCLUSIONS: Association of miltefosine with PDT mediated by topical AlClPC represents hopes for CL treatment, an increasing dermatological disease in some countries.
BACKGROUND: The shortage of drugs is a concern and has become the object of studies to discover effective alternatives for cutaneous leishmaniasis (CL) treatment. A topical formulation has been sought due to its low toxicity. Development of alternative therapies, such as multimodal ones, is important in confronting drug resistance. This study aims to compare the in vivo efficacy of topical photodynamic therapy (PDT) using liposomal chloroaluminium phthalocyanine (AlClPC) in the treatment of CL, isolated and associated with systemic therapy with miltefosine. METHODS: Five groups were adopted, each one with six isogenic adult female mice C57BL/6: (1) Negative Control-non-infected and non-treated; (2) Positive Control (PBS)-infected and non-treated; (3) Miltefosine-infected and treated with oral miltefosine 200 mg/kg/day; (4) Infected and treated with PDT with topical AlClPC (500 μL) on alternate days; (5) Oral Miltefosine 200 mg/kg/day and PDT with topical AlClPC (500 μL) on alternate days. Therapeutic schemes lasted 20 days. Infection was confirmed by culture in Nove-McNeal-Nicolle medium (NNN) of lymph collected from the animal paw, and animals were evaluated by paw measurement and parasitological criteria. RESULTS:Miltefosine associated with PDT with AlClPC promoted a significant reduction in parasite number and viability when compared to the other infected groups, also returning the paw diameter to a size similar to the negative control group after 20 days of treatment. CONCLUSIONS: Association of miltefosine with PDT mediated by topical AlClPC represents hopes for CL treatment, an increasing dermatological disease in some countries.