A standardized intraperitoneal Glucantime™ for experimental treatment of cutaneous leishmaniasis caused by Leishmania amazonensis in BALB/c mice.

Glucantime™ is the pentavalent antimony (Sb+5) recommended as the first choice for treating cutaneous leishmaniasis (CL). It has been used as treatment control in animal studies to investigate new anti-Leishmania compounds. However, these studies have a range of Glucantime™ doses, different treatment times and routes of administration, and differing results. Our goal was to standardize intraperitoneal Glucantime™ treatment for CL in BALB/c mice infected with L. amazonensis. BALB/c mice were divided into six groups, with eight animals per group. The animals were infected with L. amazonensis and intraperitoneally treated with different doses of Sb+5 (20, 100 and 200 mg/kg/day) for 30 consecutive days. Healthy animals were used as negative infection and treatment control. Infected and untreated animals were used as positive infection control. Animals infected and treated with Ampho B were used as treatment control. Biochemical and histological analysis was performed to assess renal and liver toxicity. The parasite load in the popliteal lymph node, spleen and liver was determined by limiting dilution. Histological and collagen fiber analyses were performed on the lesions. Animals treated with Sb+5 100 and 200 mg/kg/day showed a decreased paw measurements, associated with a reduction in the parasite load, with a clinical cure rate of 50% and 37.5%, respectively. These groups of animals also showed tissue regeneration and reduced inflammation. Animals treated with 100 mg/kg/day had collagen fiber parameters similar to those of the negative infection control. There were no biochemical signs of renal or liver toxicity in any of the groups. We found that Sb+5 100 mg/kg/day was the lowest dose that showed effectiveness in treating CL in mice, and it may be a good model of treatment control in studies evaluating new treatments for CL in BALB/c mice.

In vitro activity of cinnamaldehyde on Leishmania (Leishmania) amazonensis.

Tegumentary leishmaniasis is an endemic disease that urgently needs new and effective treatments. L. amazonensis is one of the main species involved in the transmission of this infectious and non-contagious disease. The currently available treatments for leishmaniasis have high toxicity and vary in efficacy. Natural compounds have been used as alternative therapies for various other diseases, often presenting excellent results with little or no adverse reaction. Cinnamaldehyde is the primary compound of essential oil from cinnamon bark; it is used in the cosmetic, pharmaceutical, and food industries for its antimicrobial and anti-inflammatory effects, as shown in the literature. As far as we know, no studies have evaluated cinnamaldehyde activity against L. amazonensis. In this context, we investigated the anti-Leishmania potential of cinnamaldehyde against promastigote and amastigote forms of L. amazonensis; cytotoxicity in erythrocytes, HaCat cells, and macrophages J774A.1; and its ability to stimulate nitric oxide. Cinnamaldehyde showed anti-Leishmania activity, with an average IC50 of approximately 212 µM against promastigote forms of L. amazonensis (three study periods: 24, 48, and 72 h) and an IC50 of 398.06 ± 42.10 µM against amastigote forms of L. amazonensis. Considerable toxicities to human erythrocytes and HaCat cells were not recorded from treatments with 4000 µM and 1000 µM of cinnamaldehyde, respectively. However, we recorded cytotoxicity with J774A.1 macrophages (0.48-1000 µM), which resulted in a low therapeutic selectivity index. The compound did not alter the production of nitric oxide in the cells evaluated. Overall, we observed that cinnamaldehyde showed anti-Leishmania activity and moderate toxicity. We encourage further research into the use of cinnamaldehyde to treat cutaneous leishmaniasis.

In vivo efficacy of meglumine antimoniate-loaded nanoparticles for cutaneous leishmaniasis: a systematic review.

Background: Nanotechnology is a promising strategy to improve existing antileishmanial agents. Objective: To explore the evidence of encapsulated meglumine antimoniate for cutaneous leishmaniasis treatment in animal models. Materials & methods: The studies were recovered from PubMed, Scopus, EMBASE, LILACS, WoS and Google according to eligibility criteria following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Population, Intervention, Comparison, Outcomes and Study design (PICOS) strategy. Study appraisal was assessed using the Animal Research Reporting of In Vivo Experiments, SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) recommendations. Results: Five studies were included. Liposomes, metallic and polymeric nanoparticles were tested in BALB/c mice against Leishmania major, L. tropica or L. amazonensis. Limitations: Few studies were found to meet the eligibility criteria. Conclusion: All formulations had a significant efficacy, similar to the meglumine antimoniate reference treatment concerning the lesion size and parasite burden. The studies had a high and moderate risk of bias, and the confidence in cumulative evidence was considered low. Therefore, we encourage the development of high-quality preclinical studies. Registration: PROSPERO register CRD42020170191.

Three decades of clinical trials on immunotherapy for human leishmaniases: a systematic review and meta-analysis.

Aim: Current treatments for leishmaniases are not satisfactory, thus alternatives are needed. We searched for clinical trials with immunotherapeutic approaches for patients with leishmaniasis. Materials & methods: Out of 205 articles, 24 clinical trials were selected, and eight submitted to meta-analysis. Results: A reduction in healing time was observed in patients with tegumentary leishmaniasis treated with pentavalent antimony plus granulocyte-macrophage colony-stimulating factor, and therapeutic vaccines. Overall meta-analysis indicated that immunotherapy associated with the standard chemotherapy generated a significantly reduced risk of treatment failure than the pentavalent antimony alone (p = 0.03). Conclusion: Our review confirmed the efficacy of immunotherapies for the treatment of cutaneous and visceral leishmaniasis and highlighted the importance of clinical trials using immunotherapies for leishmaniases.