In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection

Mendonça, Débora V.C.; Tavares, Grasiele S.V.; Lage, Daniela P.; Soyer, Tauane G.; Carvalho, Lívia M.; Dias, Daniel Lucas Santos; Ribeiro, Patrícia A.F.; Ottoni, Flaviano Melo; Antinarelli, Luciana Maria Ribeiro; Vale, Danniele L.; Ludolf, Fernanda; Duarte, Mariana C.; Coimbra, Elaine Soares; Chávez-Fumagalli, Miguel Á.; Roatt, Bruno Mendes; Menezes‐Souza, Daniel; Barichello, José Mário; Alves, Ricardo José; Coelho, Eduardo Antônio Ferraz

doi:10.1016/j.biopha.2018.10.143

Cited by 28 publications

(11 citation statements)

References 49 publications

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“…Additionally, different PL-based systems have been used as new therapeutic strategies for several purposes, such as leishmaniosis treatment. Recent reports described formulations based on PL F-127 micelles encapsulating a naphthoquinone derivative (Mendonça et al, 2019), clioquinol (Tavares et al, 2019), amphotericin B (Mendonça et al, 2016), and PL F-68 micellar systems for amphotericin B (Espuelas et al, 2000). In this study, we present the development of lipid-PL formulations containing CUR; in particular, OA has been described as an important component of skin formulations for enhanced efficacy on leishmaniosis treatment (Pinheiro et al, 2016), as well as due to its involvement on transition from promastigotes to amastigotes (Bouazizi-Ben et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery

et al. 2019

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Organogels (ORGs) are semi-solid materials, in which an organic phase is immobilized by a three-dimensional network composed of self-organized system, forming the aqueous phase. In this context, lipid–Pluronics (PLs) ORGs form a two-phase system which can be effectively used as skin delivery systems, favoring their permeation across the skin. In this study, we presented the development of ORG skin drug-delivery systems for curcumin (CUR), a liposoluble phenolic pigment extracted from the turmeric rhizome. In special, we designed the formulation compositions in order to carry high amounts of CUR soluble in oleic acid (OA), as organic phase, entrapped into an aqueous phase composed of micellar PL-based hydrogels by associating two polymers with different hydrophilic–lipophilic balances, Pluronic F-127 (PL F-127), and Pluronic L-81 (PL L-81), to enhance the permeation across the skin. Results revealed that the incorporation of PL L-81 favored the CUR incorporation into micelle–micelle interface. CUR insertion into OA-PL F-127/L-81 reduced both G’/G” relationship (∼16 x) and viscosity values (η* ∼ 54 mPa.s, at 32.5°C), disturbing the ORG network structural organization. In vitro permeation assays through Strat-M® skin-model membranes showed that higher CUR-permeated amounts were obtained for OA-PL F-127/L-81 (4.83 µg.cm−2) compared to OA-PL F-127 (3.51 μg.cm−2) and OA (2.25 μg.cm−2) or hydrogels (∼1.2 μg.cm−2, p < 0.001). Additionally, ORG formulations presented low cytotoxic effects and evoked pronounced antileishmanial activity (IC50 < 1.25 µg.ml−1), suggesting their potential use as skin delivery systems against Leishmania amazonensis. Results from this study pointed out OA-PL-based ORGs as promising new formulations for possible CUR topical administration.

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Section: Discussionmentioning

confidence: 99%

Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery

et al. 2019

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“…Disease control depends on the early diagnosis and treatment of active cases, although it is widely accepted that a prophylactic vaccine for human leishmaniosis is the way to successfully eliminate the disease. Furthermore, there is currently no acceptable vaccine for use in humans to prevent leishmaniosis [14], and conventional chemotherapies for the treatment of the disease are usually long and not effective due to the toxicity and the presence of resistance parasites [15,16]. A novel immunochemotherapy method based on L. amazonensis lysate has been recently licensed in Brazil [17].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, access to treatment in poor countries with high parasite burden is challenging. New approaches for both nanomedicine and treatment at the local site of infection are needed to reduce the toxicity and increase the accessibility of treatments [15,16,18].…”

Section: Introductionmentioning

confidence: 99%

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

et al. 2019

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Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis.

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“…Production of this cytokine by infected macrophages appears to be essential for the survival and persistence of the Leishmania parasites in their host, due to the inhibition of the protective activities in the infected cells ( Geiger et al., 2016 ; Kane and Mosser, 2001 ; Verma et al., 2016 ). A decrease in the parasite burden associated with low levels of IL-10 has been shown in BALB/c mice infected with L. amazonensis ( Mendonça et al., 2019 ). Moreover, the IL-10 secreted by T-cells influences the susceptibility of BALB/c mice to L. major infection ( Schwarz et al., 2013 ).…”

Section: Resultsmentioning

confidence: 97%

Antileishmanial activity of a new chloroquine analog in an animal model of Leishmania panamensis infection

Herrera

Llanes

Álvarez

et al. 2020

International Journal for Parasitology: Drugs and Drug Resistan

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Leishmania panamensis is a relevant causative agent of tegumentary leishmaniasis in several Latin American countries. Available antileishmanial drugs have several limitations including relatively high toxicity, difficult administration, high production costs and the emergence of resistance in circulating strains. Therefore, the identification of new molecules as potential therapeutics for leishmaniasis is of great relevance. Here, we developed a murine model of L. panamensis infection and evaluated the effect of a new compound in vivo . After treatment of animals with the compound, we observed a significant reduction of inflammation and parasite load at the inoculation site, in a dose-dependent manner. We observed a reduction in IL-10 production by popliteal lymph nodes cells of infected mice. These results pave the way for future evaluation of this compound as a potential antileishmanial drug or as a suitable scaffold for lead optimization strategies.

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In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection

Cited by 28 publications

References 49 publications

Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery

Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Antileishmanial activity of a new chloroquine analog in an animal model of Leishmania panamensis infection

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