Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment

被引:1
作者
Silva, Raphaela Ariany [1 ]
Damasio, Danielle Soter [1 ]
Coelho, Larissa Dutra [1 ]
de Morais-Teixeira, Eliane [2 ]
Queiroz-Junior, Celso M. [3 ]
Souza, Paulo Eduardo [4 ,5 ]
Azevedo, Ricardo Bentes [6 ]
Tedesco, Antonio [7 ]
Ferreira, Lucas Antonio [1 ]
Oliveira, Monica Cristina [1 ]
Aguiar, Marta Gontijo [1 ]
机构
[1] Univ Fed Minas Gerais, Fac Pharm, Dept Pharmaceut Prod, BR-31270901 Belo Horizonte, MG, Brazil
[2] Fundacao Oswaldo Cruz FIOCRUZ, Inst Rene Rachou, Clin Res & Publ Policy Grp Infect & Parasit Dis, BR-30190002 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Inst Biol Sci, Dept Morphol, BR-31270901 Belo Horizonte, MG, Brazil
[4] Univ Brasilia, Inst Phys, Lab Software & Instrumentat Appl Phys, BR-70910900 Brasilia, DF, Brazil
[5] Univ Brasilia, Inst Phys, Lab Electron Paramagnet Resonance, BR-70910900 Brasilia, DF, Brazil
[6] Univ Brasilia, Inst Biol Sci, Nanobiotechnol Lab, BR-70910900 Brasilia, DF, Brazil
[7] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeirao Preto, Ctr Nanotechnol & Tissue Engn, Dept Chem,Photobiol & Photomed Res Grp, BR-14040900 Ribeirao Preto, Brazil
关键词
chloroaluminum phthalocyanine; liposomes; fexinidazole; self-emulsifying drug release system; cutaneous leishmaniasis; combined therapy; DRUG-DELIVERY SYSTEMS; MILTEFOSINE TREATMENT; IN-VITRO; BIOAVAILABILITY; PAROMOMYCIN;
D O I
10.3390/pharmaceutics16040509
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cutaneous leishmaniasis (CL) is a neglected tropical disease. 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 < 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.
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页数:13
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