Avaliação da capacidade cicatrizante de biocurativos de celulose bacteriana no tratamento da leishmaniose tegumentar

Abstract

INTRODUCTION: Leishmaniasis is an endemic disease in Brazil, with Cutaneous Leishmaniasis (CL) being the most prevalent clinical form, characterized by a localized ulcer with high inflammatory activity. The first-choice treatment recommended by the Ministry of Health is meglumine antimoniate (MA), administered intravenously or intramuscularly for 20 consecutive days. However, the treatment with MA has limitations, including a low cure rate (50-60%) and toxicity, necessitating the search for new therapeutic approaches. Bacterial cellulose (BC) is formed by a network of cellulose fibrils, and its physicochemical properties allow it to be used as a biocurative for ulcer treatment. BC also enables the anchorage of molecules with therapeutic potential, functioning as a delivery system. In this context, we observed that sodium diethyldithiocarbamate (DETC), a SOD-1 inhibitor, was capable of reducing the parasite load in vitro and modulating lesion development in a preclinical model of cutaneous leishmaniasis caused by Leishmania braziliensis. OBJECTIVES: In this work, we aim to characterize the physicochemical properties and stability of CB-DETC biodressings and evaluate, through proof-of-concept clinical trials, the efficacy of BC biodressings as an additive treatment to AM in patients with LT caused by L. braziliensis.. MATERIALS/METHODS: Initially, we investigated the characteristics of BC-DETC using scanning electron microscopy and crystallographic profiling. We also assessed the release of DETC from the biocuratives, quantified the mass of DETC by spectrophotometry, and conducted a thermal analysis by thermogravimetry. Clinical trials were conducted in Corte de Pedra, an endemic area for CL. In the first trial, recruited patients were divided into two groups: the control group received conventional MA treatment, and the test group received MA along with topical application of BC. Both groups were treated for 20 days, and the biocuratives were replaced every two days. Cure rate, healing time, and adverse effects were evaluated at different times (15, 60, and 90 days after the end of treatment). In the second trial, we repeated the test and control groups and added a placebo group, which was treated with MA and a gauze dressing instead of BC. RESULTS: The images obtained by SEM and the crystallographic pattern of BC-DETC show that DETC is well incorporated into BC. However, release and mass quantification assays of DETC indicated instability and possible degradation, suggesting the need to stabilize DETC to sustain its release in vivo. Considering the therapeutic potential of BC, we conducted a clinical trial to evaluate the efficacy of the combined use of BC+MA. In this trial, patients treated with MA+BC showed a higher cure rate at the initial time point (60 days after the start of treatment) (p=0.01). No local adverse effects from the topical application of BC were reported, demonstrating the safety of the treatment. In the second trial, which also included a placebo group, we observed a reduction in healing time in the test and placebo groups and a reduction in the inflammatory mediator IL-1α in the test group. CONCLUSIONS: The BC-DETC system was found to be unstable for clinical applications. However, the BC biocurative combined with MA increases the cure rate in patients with CL and reduces healing time and important inflammatory mediators in CL. Modifications to the BC-DETC system should be made to enhance its stability. On the other hand, the BC biocurative shows potential for incorporation into clinical practice, positively impacting the resolution of CL.