Low doses of pharmaceutical formulations loaded with UFMG-V4N2 immunogen induce the production of IgG anti-cocaine antibodies and provide evidence of cerebral protection in the preclinical model
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Universidade Federal de Minas Gerais
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Artigo de periódico
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Membros da banca
Resumo
Anti-cocaine vaccines are a promising therapeutic strategy for treating cocaine use disorders. Here we hypothesize that nanoemulsions (NE) or suspensions (SS) loaded with the calix [4]arene-based immunogen UFMG-V4N2 can induce the production of anti-cocaine antibodies and decrease the passage of radiolabeled cocaine analog [99mTc]Trodat-1 through of the brain barrier. UFMG-V4N2 was characterized (solubility, morphology, DSC, XRD) and loaded into NEs and SSs using excipients approved for human use. Immunogenic efficacy was assessed by quantifying the titers and determining the specificity of anti-cocaine IgG antibodies, and by assessing the inhibition of [99mTc]Trodat-1 trafficking across the mice brain-barrier. UFMG-V4N2 is an amorphous, thermally stable molecule with very low hydrophilicity. The immunogenicity of NE or SS was similar, but aluminum phosphate and the lower dose of UFMG-V4N2 induced higher anti-cocaine IgG antibody titers, minimizing [99mTc]Trodat-1 uptake in the brain. Therefore, the UFMG-V4N2 may represent an alternative for the treatment of cocaine use disorder.
Abstract
Assunto
Calixarenos, Química farmacêutica, Cocaína, Vacinas
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UFMG-V4N2, Calix[4]arene-based immunogen, Pharmaceutical formulation, Anti-cocaine therapy
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https://www.sciencedirect.com/science/article/pii/S2666934X23000053?via%3Dihub