Liposomal Encapsulation of Tartar Emetic Improves Pharmacokinetic Profile and Mitigates Cardiotoxicity in Murine Experimental Model

<b>Background/Objectives:</b> Visceral leishmaniasis remains a serious public health issue, with current antimonial therapies limited by systemic toxicity. Liposomal drug delivery systems offer a promising strategy to improve therapeutic outcomes. In this context, we previously demonstrated the antileishmanial efficacy of the liposomal formulation containing tartar emetic (Lip-TE) in reducing the parasite load in the spleen and liver of animals experimentally infected with <i>Leishmania (Leishmania) infantum</i>, this being an interesting alternative for the treatment of visceral leishmaniasis. In this study, we aimed to evaluate the physicochemical properties, biodistribution, pharmacokinetics, and cardiotoxicity of Lip-TE. <b>Methods:</b> Both Lip-Blank and Lip-TE exhibited monodisperse size distributions (PDI < 0.3), with Lip-TE having an increased particle size (205.1 ± 4.5 nm) compared to Lip-Blank (137.5 ± 0.8 nm). Both formulations demonstrated a positive zeta potential of about +17.0 mV. Biodistribution and cardiotoxicity studies were performed using female BALB/c mice, approximately 8 to 10 weeks old. <b>Results:</b> A significantly greater splenic, hepatic, and renal accumulation of Lip-TE was observed, particularly at 120 min post-injection, compared to Free TE treatment. The pharmacokinetic profile of the treatment with Lip-TE showed higher systemic exposure (AUC), extended half-life and mean residence time, and reduced clearance compared to Free TE treatment. Echocardiographic analysis revealed that treatment with Free TE significantly reduced the ejection fraction percentage and QRS complex prolongation after 10 days of treatment. These alterations persisted at 30 days, indicating progressive cardiotoxicity. In contrast, Lip-TE treatment preserved cardiac function, revealing the protective effect of the liposomal encapsulation. <b>Conclusions:</b> These findings highlight the potential of the Lip-TE treatment to enhance safety and efficacy.