Diethyldithiocarbamate encapsulation reduces toxicity and promotes leishmanicidal effect through apoptosis-like mechanism in promastigote and ROS production by macrophage. (25th November 2020)

• Record Type: Journal Article
• Authors: Assolini, João Paulo; Tomiotto-Pellissier, Fernanda; da Silva Bortoleti, Bruna Taciane; Gonçalves, Manoela Daiele; Sahd, Claudia Stoeglehner; Carloto, Amanda Cristina Machado; Feuser, Paulo Emilio; Cordeiro, Arthur Poester; Borghi, Sergio Marques; Verri, Waldiceu Aparecido; Sayer, Claudia; Hermes de Araújo, Pedro Henrique; Costa, Idessania Nazareth; Conchon-Costa, Ivete; Miranda-Sapla, Milena Menegazzo; Pavanelli, Wander Rogério
• Is Part Of: Journal of drug targeting. Volume 28:Number 10(2020)
• Page Start: 1110
• Page End: 1123
• Publication Date: 2020-11-25
• Subjects: Leishmaniasis -- solid lipid nanoparticle -- reactive oxygen species -- cytokines -- nanotechnology; Drug delivery systems -- Periodicals; Drug Delivery Systems; Vehicles; Drug Administration Routes; Drug Evaluation; 615.7
• DOI: 10.1080/1061186X.2020.1783669
• Languages: English
• ISSNs: 1061-186X

Abstract

Abstract: The use of compounds from natural or synthetic sources and nanotechnology may represent an alternative to develop new drugs for the leishmaniasis treatment. DETC is an inhibitor of the SOD1 enzyme, which leads to increased ROS production, important for the elimination of Leishmania . Thus, our objective was to assess the leishmanicidal in vitro effect of free Diethydithiocarbamate (DETC) and DETC loaded in beeswax-copaiba oil nanoparticles (DETC-Beeswax-CO Nps) on L. amazonensis forms and elucidate the possible mechanisms involved in the parasite death. DETC-Beeswax-CO Nps presented size below 200 nm, spherical morphology, negative zeta potential, and high encapsulation efficiency. Free DETC reduced the viability of promastigotes and increase ROS production, lower the mitochondrial membrane potential, cause phosphatidylserine exposure, and enhance plasma membrane permeability, in addition to promoting morphological changes in the parasite. Free DETC proved toxic in the assessment of toxicity to murine macrophages, however, the encapsulation of this compound was able to reduce these toxic effects on macrophages. DETC-Beeswax-CO Nps exerted anti-amastigote effect by enhancing the production of ROS, superoxide anion, TNF-α, IL-6, and reduced IL-10 in macrophages. Therefore, free DETC induces antipromastigote effect by apoptosis-like; and DETC-Beeswax-CO Nps exerted anti-leishmanial effect due to pro-oxidant and pro-inflammatory response.