Calix[n]arene-based immunogens: a new non-proteic strategy for anti-cocaine vaccine
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2022
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Introduction: Cocaine use disorder is a significant public health issue without a current specific approved
treatment. Among different approaches to this disorder, it is possible to highlight a promising immunologic strategy in which an immunogenic agent may reduce the reinforcing effects of the drug if they are
able to yield sufficient specific antibodies capable to bind cocaine and/or its psychoactive metabolites
before entering into the brain. Several carriers have been investigated in the anti-cocaine vaccine development; however, they generally present a very complex chemical structure, which potentially hampers
the proper assessment of the coupling efficiency between the hapten units and the protein structure.
Objectives: The present study reports the design, synthesis and preclinical evaluation of two novel calix
[n]arene-based anti-cocaine immunogens (herein named as V4N2 and V8N2) by the tethering of the
hydrolysis-tolerant hapten GNE (15) on calix[4]arene and calix[8]arene moieties.
Methods: The preclinical assessment corresponded to the immunogenicity and dose–response evaluation
of V4N2 and V8N2. The potential of the produced antibodies to reduce the passage of cocaine analogue
through the blood–brain-barrier (BBB), modifying its biodistribution was also investigated.
Results: Both calix[n]arene-based immunogens elicited high titers of cocaine antibodies that modified the
biodistribution of a cocaine radiolabeled analogue (99mTc-TRODAT-1) and decreased cocaine-induced
behavior, according to an animal model.
Conclusion: The present results demonstrate the potential of V4N2 and V8N2 as immunogens for the
treatment of cocaine use disorder.
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Cocaine, Crack, Chemical addiction, Calixarenes, Immunotherapy, TRODAT-1
Citação
SILVA NETO, Leonardo da et al. Calix[n]arene-based immunogens: a new non-proteic strategy for anti-cocaine vaccine. Journal of Advanced Research, Amsterdam, v. 38, p. 285-298, 2022. DOI: 10.1016/j.jare.2021.09.003. Disponível em: https://www.sciencedirect.com/science/article/pii/S2090123221001715?via%3Dihub. Acesso em: 30 nov. 2023.