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https://www.arca.fiocruz.br/handle/icict/62216
BACTERIAL CELLULOSE BIOCURATIVES FOR THE TOPICAL TREATMENT OF CUTANEOUS LEISHMANIASIS
Author
Affilliation
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil.
Universidade de Araraquara. Araraquara, SP, Brasil.
Serviço de Imunologia, HUPES-UFBA. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil.
Universidade de Araraquara. Araraquara, SP, Brasil.
Serviço de Imunologia, HUPES-UFBA. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil.
Fundação Oswaldo. Instituto Gonçalo Muniz. Salvador, BA, Brasil / Instituto de Investigação em Doenças Tropicais. Salvador, BA, Brasil.
Abstract
In Brazil, cutaneous leishmaniasis (CL) is mainly caused by Leishmania braziliensis. Pentavalent antimonials (Sbv) remain the first-line drug on treatment for CL despite the limitations regarding toxicity and increasing reports of therapeutic failure. Therefore, the search for alternative options for treatment that are safe, efficient and of easy application remains necessary. We have show that DETC, a SOD1 inhibitior, in association with a bacterial cellulose (BC) biocurative, reduced parasite burden and inhibited lesion development in a pre clinical model of CL caused by L. braziliensis. We thus hypothesized that BC biocuratives in association with DETC (BC-DETC) could act in conjuction with pentavalent antimonials to reduce the burden of disease in CL patients. To this end, we performed physicochemical characterization of BC-DETC employing scanning electron microscopy (SEM) and x-ray diffraction (XRD). In addition, we performed an in vitro release assay by spectrophotometry and evaluated the stability of DETC onto BC by spectrophotometry and thermogravimetry. SEM images of BC- DETC showed DETC aggregates across the entire surface. The absence of crystallographic peaks, seen by XRD analysis, indicated that DETC was succesfully incorporated onto BC biocuratives. In vitro release experiments showed a accumulative mass release of 22% and 14%, at 5 minutes and 24 hours, respectively, indicating possible degradation of DETC. Thermogravimetry analysis complemented our findings that strongly indicating that DETC is not stable when incorporated onto BC. Despite our results showing that DETC is short lived when incorportated onto BC, as suggested by degradation experiments, we performed an initial a pilot, proof-of-concept trial, to evaluate the efficacy of topical application of BC in CL patients. A total of 20 patients were randomized in two groups assigned to receive either parenteral Sbv alone or parenteral Sbv plus topically applied BC bio-curatives. CL patients treated with Sbv + topical BC bio- curatives had a significantly higher cure rate at 60 days post initiation of treatment compared to CL patients treated with Sbv alone (P=0.01). At day 90 post initiation of treatment, cure rate was similar in the two groups as was overall healing time. Adverse effects or local reactions to topical BC application were not observed. This pilot trial shows that the potential use of a combined therapy consisting of topical BC bio-curatives and parenteral Sbv in favoring healing of CL lesions caused by L. braziliensis, at an early time point.
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