by Keyword: Artemisinin

Avalos-Padilla, Y, Fernandez-Busquets, X, (2024). Nanotherapeutics against malaria: A decade of advancements in experimental models Wiley Interdisciplinary Reviews-Nanomedicine And Nanobiotechnology 16, e1943

Malaria, caused by different species of protists of the genus Plasmodium, remains among the most common causes of death due to parasitic diseases worldwide, mainly for children aged under 5. One of the main obstacles to malaria eradication is the speed with which the pathogen evolves resistance to the drug schemes developed against it. For this reason, it remains urgent to find innovative therapeutic strategies offering sufficient specificity against the parasite to minimize resistance evolution and drug side effects. In this context, nanotechnology-based approaches are now being explored for their use as antimalarial drug delivery platforms due to the wide range of advantages and tuneable properties that they offer. However, major challenges remain to be addressed to provide a cost-efficient and targeted therapeutic strategy contributing to malaria eradication. The present work contains a systematic review of nanotechnology-based antimalarial drug delivery systems generated during the last 10 years. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

JTD Keywords: Adjuvant system, Antimalarial activities, Antimalarial agent, Antimalarial drug, Antimalarial drugs, Antimalarials, Artemisinin resistance, Causes of death, Child, Controlled drug delivery, Diseases, Drug delivery system, Drug delivery systems, Drug interactions, Drug side-effects, Drug-delivery, Experimental modelling, Heparan-sulfate, Human, Humans, In-vitro, Malaria, Malaria vaccine, Mannosylated liposomes, Medical nanotechnology, Models, theoretical, Nanocarriers, Nanomedicine, Nanotechnology, Parasite-, Parasitics, Plasmodium, Plasmodium-falciparum malaria, Red-blood-cells, Targeted delivery, Targeted drug delivery, Theoretical model, Therapeutic strategy

Fulgheri, F, Manca, ML, Fernàndez-Busquets, X, Manconi, M, (2023). Analysis of complementarities between nanomedicine and phytodrugs for the treatment of malarial infection Nanomedicine 18, 1681-1696

The use of nanocarriers in medicine, so-called nanomedicine, is one of the most innovative strategies for targeting drugs at the action site and increasing their activity index and effectiveness. Phytomedicine is the oldest traditional method used to treat human diseases and solve health problems. The recent literature on the treatment of malaria infections using nanodelivery systems and phytodrugs or supplements has been analyzed. For the first time, in the present review, a careful look at the considerable potential of nanomedicine in promoting phytotherapeutic efficacy was done, and its key role in addressing a translation through a significant reduction of the current burden of malaria in many parts of the world has been underlined.

JTD Keywords: antiplasmodial activity, bioavailability, chloroquine, combination therapy, discovery, drug-delivery, drug-delivery systems, nanocapsules, nanomedicine, natural molecules, pharmacokinetics, phytomedicine, plasmodium-falciparum, Artemisinin-based combination therapy, Drug-delivery systems, Nanomedicine, Natural molecules, Phytomedicine, Solid lipid nanoparticles

Fonte, M, Fontinha, D, Moita, D, Caño-Prades, O, Avalos-Padilla, Y, Fernàndez-Busquets, X, Prudencio, M, Gomes, P, Teixeira, C, (2023). New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial leads European Journal Of Medicinal Chemistry 258, 115575

A novel family of 4-aminoacridine derivatives was obtained by linking this heteroaromatic core to different trans-cinnamic acids. The 4-(N-cinnamoylbutyl)aminoacridines obtained exhibited in vitro activity in the low- or sub-micromolar range against (i) hepatic stages of Plasmodium berghei, (ii) erythrocytic forms of Plasmodium falciparum, and (iii) early and mature gametocytes of Plasmodium falciparum. The most active compound, having a meta-fluorocinnamoyl group linked to the acridine core, was 20- and 120-fold more potent, respectively, against the hepatic and gametocyte stages of Plasmodium infection than the reference drug, primaquine. Moreover, no cytotoxicity towards mammalian and red blood cells at the concentrations tested was observed for any of the compounds under investigation. These novel conjugates represent promising leads for the development of new multi-target antiplasmodials.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

JTD Keywords: agents, analogs, antimalarial, artemisinin, blood-stage, cinnamic acid, gametocyte, hybrid, liver-stage, malaria, multi-target, plasmodium-falciparum, primaquine, quinacrine, resistance, Acridine, Antimalarial, Blood-stage, Cinnamic acid, Cinnamic acid-derivatives, Gametocyte, Hybrid, Liver-stage, Multi-target

Fulgheri, F, Aroffu, M, Ramírez, M, Román-Alamo, L, Peris, JE, Usach, I, Nacher, A, Manconi, M, Fernàndez-Busquets, X, Manca, ML, (2023). Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections International Journal Of Pharmaceutics 643, 123195

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around -8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.Copyright © 2023. Published by Elsevier B.V.

JTD Keywords: artemisinin, delivery, flavonol, formulations, liposomes, malaria infections, nanomedicine, nutriose (r) fm06, oral administration, plasmodium falciparum, In-vitro, Liposomes, Malaria infections, Nanomedicine, Nutriose® fm06, Oral administration, Plasmodium falciparum

Biosca, A, Ramirez, M, Gomez-Gomez, A, Lafuente, A, Iglesias, V, Pozo, OJ, Imperial, S, Fernandez-Busquets, X, (2022). Characterization of Domiphen Bromide as a New Fast-Acting Antiplasmodial Agent Inhibiting the Apicoplastidic Methyl Erythritol Phosphate Pathway Pharmaceutics 14, 1320

The evolution of resistance by the malaria parasite to artemisinin, the key component of the combination therapy strategies that are at the core of current antimalarial treatments, calls for the urgent identification of new fast-acting antimalarials. The apicoplast organelle is a preferred target of antimalarial drugs because it contains biochemical processes absent from the human host. Fosmidomycin is the only drug in clinical trials targeting the apicoplast, where it inhibits the methyl erythritol phosphate (MEP) pathway. Here, we characterized the antiplasmodial activity of domiphen bromide (DB), another MEP pathway inhibitor with a rapid mode of action that arrests the in vitro growth of Plasmodium falciparum at the early trophozoite stage. Metabolomic analysis of the MEP pathway and Krebs cycle intermediates in 20 mu M DB-treated parasites suggested a rapid activation of glycolysis with a concomitant decrease in mitochondrial activity, consistent with a rapid killing of the pathogen. These results present DB as a model compound for the development of new, potentially interesting drugs for future antimalarial combination therapies.

JTD Keywords: antibiotics, antimalarial drugs, domiphen bromide, malaria, plasmodium falciparum, Antibiotics, Antimalarial drugs, Antimalarial-drug, Artemisinin, Combination therapies, Domiphen bromide, Intraerythrocytic stages, Isoprenoid biosynthesis, Malaria, Methyl erythritol phosphate pathway, Nonmevalonate pathway, Plasmodium falciparum, Plasmodium-falciparum apicoplast, Red-blood-cells, Targeted delivery

Caddeo, C, Gabriele, M, Nácher, A, Fernàndez-Busquets, X, Valenti, D, Fadda, AM, Pucci, L, Manconi, M, (2021). Resveratrol and artemisinin eudragit-coated liposomes: A strategy to tackle intestinal tumors International Journal Of Pharmaceutics 592, 120083

© 2020 Elsevier B.V. Resveratrol and artemisinin, two naturally occurring compounds with a wide range of biological activities, have been reported to exert antitumor effects against several types of cancer. In this work, Eudragit-coated liposomes were developed to safely transport resveratrol and artemisinin through the gastrointestinal tract and target the intestine. The physico-chemical properties of the Eudragit-coated liposomes were assessed by light scattering and cryogenic transmission electron microscopy. Nanosized (around 100 nm), spherical or elongated, unilamellar vesicles were produced. The protective effect of the Eudragit coating was confirmed by assessing the physical stability of the vesicles in fluids mimicking the gastrointestinal environment. Furthermore, the vesicles were found to exert a pro-oxidant activity in intestinal adenocarcinoma cells, which resulted in a marked mortality due to the generation of reactive oxygen species (ROS). A time- and dose-dependent cell growth inhibitory effect was detected, with elevated ROS levels when resveratrol and artemisinin were combined. Therefore, the proposed formulations may represent a valuable means to counteract intestinal tumor growth.

JTD Keywords: antitumor, artemisinin, eudragit, intestinal delivery, liposomes, Antitumor, Artemisinin, Eudragit, Intestinal delivery, Liposomes, Resveratrol