Use of Combined Chemotherapy with Etoposide and Methotrexate, both Associated to Lipid Nanoemulsions for Atherosclerosis Treatment in Cholesterol-fed Rabbits

Abstract

Compared to the single treatments with LDE-methotrexate and LDE-etoposide, the combined treatment was more effective in reducing the atherosclerotic lesions. Because the toxicity of the novel drug-target combined scheme was low, those results favor the possibility of future clinical studies in patients with cardiovascular disease.

Methotraxate‐Loaded Hybrid Nanoconstructs Target Vascular Lesions and Inhibit Atherosclerosis Progression in ApoE−/− Mice

“…All mice were kept on HFD for the whole duration of the experiment and plaque coverage was quantified via Sudan IV staining. Importantly, only ≈1 mg kg −1 of MTX was injected, free or via SPNs, which is four times lower than what documented in the literature so far …”

Targeting inflammation to reduce cardiovascular disease risk: a realistic clinical prospect?

“…Indeed, methotrexate (4 mg·kg −1 ) intravenously injected four times a week for 30 days has been shown to reduce by 75% atherosclerosis formation in rabbits (Bulgarelli et al, ). In addition, administration of methotrexate alone or in combination with etoposide carried in lipid nanoemulsion reduced macrophage, MMP‐9 and lesional content of proinflammatory cytokines, again in the atherosclerotic rabbit model (Bulgarelli et al, ; Leite et al, ).…”

Tissue Uptake Mechanisms Involved in the Clearance of Non‐Protein Nanoparticles that Mimic LDL Composition: A Study with Knockout and Transgenic Mice

“…This finding made room for the use of LDE as vehicles for chemotherapeutic agents in cancer treatment, aiming to concentrate those agents into neoplastic tissues and increase their pharmacologic action while decreasing their toxicity [7,[9][10][11]. In fact, treatment of rabbits with atherosclerosis with preparations of drugs associated with LDE, such as paclitaxel [12], etoposide [13], methotrexate [14] or their combination [15] and carmustine [16] resulted in pronounced reduction of the lesions and the plaque-associated inflammatory and proliferative processes. In fact, treatment of rabbits with atherosclerosis with preparations of drugs associated with LDE, such as paclitaxel [12], etoposide [13], methotrexate [14] or their combination [15] and carmustine [16] resulted in pronounced reduction of the lesions and the plaque-associated inflammatory and proliferative processes.…”

“…The drastic reduction of the toxicity of anti-cancer agents, as observed in experimental animals and patients with advanced cancers [10], lead to another pioneer proposal: using preparations of anti-cancer drugs carried in the nanoparticles to treat atherosclerosis. In fact, treatment of rabbits with atherosclerosis with preparations of drugs associated with LDE, such as paclitaxel [12], etoposide [13], methotrexate [14] or their combination [15] and carmustine [16] resulted in pronounced reduction of the lesions and the plaque-associated inflammatory and proliferative processes. Used in a rabbit model of heart transplantation and graft vasculopathy, the preparation of paclitaxel carried in LDE had the ability to diminish the post-transplantation damages to the grafted heart [17].…”