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http://hdl.handle.net/1843/51816
Type: | Artigo de Periódico |
Title: | Calix[n]arene-based immunogens: a new non-proteic strategy for anti-cocaine vaccine |
Authors: | Leonardo da Silva Neto Angélica Faleiros da Silva Maia Adriana Martins Godin Paulo Sérgio de Almeida Augusto Raissa Lima Gonçalves Pereira Sordaini Maria Caligiorne Rosemeire Brondi Alves Simone Odília Antunes Fernandes Valbert Nascimento Cardoso Gisele Assis Castro Goulart Felipe Terra Martins Maila de Castro Lourenço das Neves Frederico Duarte Garcia Ângelo de Fátima |
Abstract: | 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. |
Subject: | Cocaína Dependência química Imunoterapia |
language: | eng |
metadata.dc.publisher.country: | Brasil |
Publisher: | Universidade Federal de Minas Gerais |
Publisher Initials: | UFMG |
metadata.dc.publisher.department: | FAR - DEPARTAMENTO DE ALIMENTOS FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS MED - DEPARTAMENTO DE SAÚDE MENTAL |
Rights: | Acesso Aberto |
metadata.dc.identifier.doi: | https://doi.org/10.1016/j.jare.2021.09.003 |
URI: | http://hdl.handle.net/1843/51816 |
Issue Date: | May-2022 |
metadata.dc.url.externa: | https://www.sciencedirect.com/science/article/pii/S2090123221001715 |
metadata.dc.relation.ispartof: | Journal of Advanced Research |
Appears in Collections: | Artigo de Periódico |
Files in This Item:
File | Description | Size | Format | |
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Calix[n]arene-based immunogens A new non-proteic strategy for anti-cocaine vaccine.pdf | 2.27 MB | Adobe PDF | View/Open |
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