Chloroquine endosomal escape mechanism

Discussion in 'Canada Drug' started by frig, 10-Mar-2020.

  1. m412 Well-Known Member

    Chloroquine endosomal escape mechanism


    Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it.

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    Dendronized Mesoporous Silica Nanoparticles Provide an Internal Endosomal Escape Mechanism for Successful Cytosolic Drug Release Veronika Weiss,a Christian Argyo,a Adriano A. Torrano,a Claudia Strobel,b Stephan A. Mackowiak,a Tim Gatzenmeier,a Ingrid Hilger,b Christoph Bräuchle,a* and Thomas Bein a* a Department of Physical Chemistry and Center of NanoScience CeNS, University of Munich LMU, Highlights The background mechanisms of endosomal escape are studied. Large unilamellar vesicles with membrane inserted bacteriorhodopsin were used. Fluorescein-labeled cell-penetrating peptides were encapsulated inside the vesicles. Light-induced pH gradient by bacteriorhodopsin caused peptide membrane translocation. The response to the pH gradient was stronger for more hydrophobic peptides. Some gene delivery methods naturally induce endosomal escape, such as adeno-associated virus AAV. For those methods that do not have such a capability, endosomal escape can be achieved by using various endosome-disruptive approaches. One approach is to treat cells with small chemicals, such as Ca 2+, chloroquine, and sucrose.

    The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead.

    Chloroquine endosomal escape mechanism

    Endosomal Escape Pathways for Non-Viral Nucleic Acid Delivery Systems., Modeling the endosomal escape of cell-penetrating peptides using a.

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  4. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. In this thesis, I designed and implemented a screen to discover small molecules and peptides that enhance the endosomal escape of proteins fused to superpositively charged GFP +36 GFP.

    • The Discovery and Characterization of Endosomal Escape..
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    Unfortunately, Chloroquine, as well as other endosomal escape or endolytic agents, are often too toxic for use in preclinical models or eventual clinical trials of macromolecular therapeutics. Alternatively, viruses have evolutionarily addressed the endosomal escape problem by destabilizing the endosomal lipid bilayer membrane by insertion of motifs containing hydrophobic amino acid R groups 22. Endosomal escape mechanisms of polyplexes and liposomes. chloroquine failed to inhibit the endosomal escape of complexes. These results could be attributed to the concentration used in the current study 50 μM, as chloroquine has been shown to raise endosomal pH levels at concentrations over 0.6 M. However, it is possible that HaCat cells. Malaria. Chloroquine has long been used in the treatment or prevention of malaria from Plasmodium vivax, P. ovale, and P. malariae, excluding the malaria parasite Plasmodium falciparum, for it started to develop widespread resistance to it. Chloroquine has been extensively used in mass drug administrations.

     
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