by Keyword: plasmodium-falciparum
Hamelmann NM, Paats JD, Avalos-Padilla Y, Lantero E, Spanos L, Siden-Kiamos I, Fernàndez-Busquets X, Paulusse JMJ, (2023). Single-Chain Polymer Nanoparticles Targeting the Ookinete Stage of Malaria Parasites Acs Infectious Diseases 9, 56-64
Malaria is an infectious disease transmitted by mosquitos, whose control is hampered by drug resistance evolution in the causing agent, protist parasites of the genus Plasmodium, as well as by the resistance of the mosquito to insecticides. New approaches to fight this disease are, therefore, needed. Research into targeted drug delivery is expanding as this strategy increases treatment efficacies. Alternatively, targeting the parasite in humans, here we use single-chain polymer nanoparticles (SCNPs) to target the parasite at the ookinete stage, which is one of the stages in the mosquito. This nanocarrier system provides uniquely sized and monodispersed particles of 5-20 nm, via thiol-Michael addition. The conjugation of succinic anhydride to the SCNP surface provides negative surface charges that have been shown to increase the targeting ability of SCNPs to Plasmodium berghei ookinetes. The biodistribution of SCNPs in mosquitos was studied, showing the presence of SCNPs in mosquito midguts. The presented results demonstrate the potential of anionic SCNPs for the targeting of malaria parasites in mosquitos and may lead to progress in the fight against malaria.
JTD Keywords: antimalarial, atovaquone, carriers, delivery, drug-conjugate, heparin, intramolecular crosslinking, plasmodium berghei, therapy, thiol-michael addition, transmission, Atovaquone, Drug-conjugate, Intramolecular crosslinking, Plasmodium berghei, Plasmodium-falciparum, Single chain polymer nanoparticles, Thiol-michael addition
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, 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
Guasch-Girbau A, Fernàndez-Busquets X, (2021). Review of the current landscape of the potential of nanotechnology for future malaria diagnosis, treatment, and vaccination strategies Pharmaceutics 13,
Malaria eradication has for decades been on the global health agenda, but the causative agents of the disease, several species of the protist parasite Plasmodium, have evolved mechanisms to evade vaccine-induced immunity and to rapidly acquire resistance against all drugs entering clinical use. Because classical antimalarial approaches have consistently failed, new strategies must be explored. One of these is nanomedicine, the application of manipulation and fabrication technology in the range of molecular dimensions between 1 and 100 nm, to the development of new medical solutions. Here we review the current state of the art in malaria diagnosis, prevention, and therapy and how nanotechnology is already having an incipient impact in improving them. In the second half of this review, the next generation of antimalarial drugs currently in the clinical pipeline is presented, with a definition of these drugs’ target product profiles and an assessment of the potential role of nanotechnology in their development. Opinions extracted from interviews with experts in the fields of nanomedicine, clinical malaria, and the economic landscape of the disease are included to offer a wider scope of the current requirements to win the fight against malaria and of how nanoscience can contribute to achieve them. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
JTD Keywords: antibody-bearing liposomes, antimalarial drugs, combination therapies, drug-delivery strategies, malaria diagnosis, malaria prophylaxis, malaria therapy, nanocarriers, nanomedicine, nanoparticles, nanotechnology, plasmodium, plasmodium-falciparum, red-blood-cells, targeted delivery, targeted drug delivery, vitro antimalarial activity, Antimalarial drugs, Isothermal amplification lamp, Malaria diagnosis, Malaria prophylaxis, Malaria therapy, Nanocarriers, Nanomedicine, Nanotechnology, Plasmodium, Targeted drug delivery