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논문 기본 정보

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학술저널
저자정보
Leal Pinto Sandra Milena (Universidad de Santander Facultad de Ciencias de la Salud Bucaramanga Colombia.) Muehlmann Luis Alexandre (Laboratory of Nanoscience and Immunology Faculty of Ceilandia University of Brasilia Brasilia/DF Br) Ojeda Lucia Liliana Mantilla (Universidad de Santander Facultad de Ciencias de la Salud Bucaramanga Colombia.) Vera Arias Angelica Maria (Centro de Investigacion en Enfermedades Tropicales (CINTROP-UIS) Departamento de Ciencias Basicas E) Cordero Martha Viviana Roa (Universidad de Santander Facultad de Ciencias de la Salud Bucaramanga Colombia.) Santos Maria de Fatima Menezes Almeida (Department of Genetics and Morphology Institute of Biological Science University of Brasilia Brasil) Azevedo Ricardo Bentes (Department of Genetics and Morphology Institute of Biological Science University of Brasilia Brasil) Rivero Patricia Escobar (Centro de Investigacion en Enfermedades Tropicales (CINTROP-UIS) Departamento de Ciencias Basicas E)
저널정보
대한감염학회 Infection and Chemotherapy Infection and Chemotherapy 제53권 제2호
발행연도
2021.1
수록면
342 - 354 (13page)

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Background Photodynamic therapy (PDT) using chloroaluminium phthalocyanine (ClAlPc) and paromomycin sulfate (PM) can be effective against New World Leishmania species involved in cutaneous leishmaniasis (CL). The aim of this study is to assay the skin permeation and the antileishmanial effects of a nanoemulsion (NE) containing both ClAlPc and PM in experimental CL by Leishmania (Viannia) braziliensis. Material and Methods Cremophor ELP/castor oil-based NEs were prepared by a low-energy method and characterized for their physicochemical parameters. The NEs were used to deliver both ClAlPc and PM to leishmania cells. The in vitro toxicity of NEs were tested in vitro against L. (V.) braziliensis and THP-1 cells. The in vivo toxicity was assessed in non-infected BALB/c mice. Ex-vivo permeation and retention studies using healthy mice skin were also conducted. Finally, the in vivo activity of NE-PM+ClAlPc after PDT was tested in BALB/c mice infected with parasites. Results NEs are colloidally stable with average droplet diameter of 30 nm, polydispersity index (PDI) below 0.2, and zeta potential near zero. Both promastigotes and intracellular amastigotes treated with NE-PM, NE-ClAlPc and NE-PM+ClAlPc were inhibited at >50%, >95%, >88%, respectively, after PDT with a phototoxic index (PI) >1.2. No skin ClAlPc permeation was observed. In contrast, PM skin permeation was 80-fold higher using PM-loaded NE formulation in comparison to aqueous PM solution. Topical treatment with NE formulations showed no signs of local toxicity or genotoxicity. In addition, concentrations of PM between 27.3 - 292.5 μM/25 mg of tissue were detected in different organs. In vivo, the NE-PM+ClAlPc treatment did not reduce skin lesions. Conclusion The Cremophor ELP/castor oil NE formulation increases the permeation of PM through the skin and can be used to co-deliver PM plus ClAlPc for combined PDT protocols. However, the lack of efficacy in the in vivo model evidences that the therapeutical scheme has to be improved.

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