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The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg\/kg\/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg\/kg\/day) combination; 4. FEX suspension (50 mg\/kg\/day); and 5. control (untreated). BALB\/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p &lt; 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.<\/jats:p>","DOI":"10.3390\/pharmaceutics16040509","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:11:55Z","timestamp":1712571115000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment"],"prefix":"10.3390","volume":"16","author":[{"given":"Raphaela Ariany","family":"Silva","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle Soter","family":"Damasio","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4119-8696","authenticated-orcid":false,"given":"Larissa Dutra","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"de Morais-Teixeira","sequence":"additional","affiliation":[{"name":"Clinical Research and Public Policy Group on Infectious and Parasitic Diseases, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz\u2014FIOCRUZ, Belo Horizonte 330190-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso M.","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Eduardo","family":"Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Software and Instrumentation in Applied Physics and Laboratory of Electron Paramagnetic Resonance, Institute of Physics, University of Bras\u00edlia, Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-9588","authenticated-orcid":false,"given":"Ricardo Bentes","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Nanobiotechnology Laboratory, Institute of Biological Sciences, University of Bras\u00edlia, Bras\u00edlia 70910-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4198-9321","authenticated-orcid":false,"given":"Ant\u00f4nio","family":"Tedesco","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center of Nanotechnology and Tissue Engineering\u2014Photobiology and Photomedicine Research Group, Faculty of Philosophy, Sciences and Letters of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Ant\u00f4nio","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica Cristina","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3820-2842","authenticated-orcid":false,"given":"Marta Gontijo","family":"Aguiar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,7]]},"reference":[{"key":"ref_1","unstructured":"(2023, April 07). 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