Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom

This study assesses the efficacy of different nanoemulsion formulations as new and innovative adjuvants for improving the in vivo immunization against the <i>Tityus serrulatus</i> scorpion venom. Nanoemulsions were designed testing key-variables such as surfactants, co-solvents, and the...

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Main Authors: Arthur Sérgio Avelino de Medeiros, Manoela Torres-Rêgo, Ariane Ferreira Lacerda, Hugo Alexandre Oliveira Rocha, Eryvaldo Sócrates Tabosa do Egito, Alianda Maira Cornélio, Denise V. Tambourgi, Matheus de Freitas Fernandes-Pedrosa, Arnóbio Antônio da Silva-Júnior
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/12/10/927
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author Arthur Sérgio Avelino de Medeiros
Manoela Torres-Rêgo
Ariane Ferreira Lacerda
Hugo Alexandre Oliveira Rocha
Eryvaldo Sócrates Tabosa do Egito
Alianda Maira Cornélio
Denise V. Tambourgi
Matheus de Freitas Fernandes-Pedrosa
Arnóbio Antônio da Silva-Júnior
author_facet Arthur Sérgio Avelino de Medeiros
Manoela Torres-Rêgo
Ariane Ferreira Lacerda
Hugo Alexandre Oliveira Rocha
Eryvaldo Sócrates Tabosa do Egito
Alianda Maira Cornélio
Denise V. Tambourgi
Matheus de Freitas Fernandes-Pedrosa
Arnóbio Antônio da Silva-Júnior
author_sort Arthur Sérgio Avelino de Medeiros
collection DOAJ
description This study assesses the efficacy of different nanoemulsion formulations as new and innovative adjuvants for improving the in vivo immunization against the <i>Tityus serrulatus</i> scorpion venom. Nanoemulsions were designed testing key-variables such as surfactants, co-solvents, and the influence of the temperature, which would be able to induce the phase transition from a liquid crystal to a stable nanoemulsion, assessed for four months. Additionally, cationic-covered nanoemulsion with hyper-branched poly(ethyleneimine) was prepared and its performance was compared to the non-cationic ones. The physicochemical properties of the selected nanoemulsions and the interactions among their involved formulation compounds were carefully monitored. The cytotoxicity studies in murine macrophages (RAW 264.7) and red blood cells were used to compare different formulations. Moreover, the performance of the nanoemulsion systems as biocompatible adjuvants was evaluated using mice immunization protocol. The FTIR shifts and the zeta potential changes (from −18.3 ± 1.0 to + 8.4 ± 1.4) corroborated with the expected supramolecular anchoring of venom proteins on the surface of the nanoemulsion droplets. Cell culture assays demonstrated the non-toxicity of the formulations at concentrations less than 1.0 mg/mL, which were able to inhibit the hemolytic effect of the scorpion venom. The cationic-covered nanoemulsion has shown superior adjuvant activity, revealing the highest IgG titer in the immunized animals compared to both the non-cationic counterpart and the traditional aluminum adjuvant. In this approach, we demonstrate the incredible potential application of nanoemulsions as adjuvants, using a nanotechnology platform for antigen delivery system on immune cells. Additionally, the functionalization with hyper-branched poly(ethyleneimine) enhances this recognition and improves its action in immunization.
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spelling doaj.art-8e5558bca6074173b743819fe657a7ec2023-11-20T15:28:14ZengMDPI AGPharmaceutics1999-49232020-09-01121092710.3390/pharmaceutics12100927Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion VenomArthur Sérgio Avelino de Medeiros0Manoela Torres-Rêgo1Ariane Ferreira Lacerda2Hugo Alexandre Oliveira Rocha3Eryvaldo Sócrates Tabosa do Egito4Alianda Maira Cornélio5Denise V. Tambourgi6Matheus de Freitas Fernandes-Pedrosa7Arnóbio Antônio da Silva-Júnior8Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilLaboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilLaboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilDepartment of Biochemistry, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilLaboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilDepartment of Morphology, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilLaboratory of Immunochemistry, Butantan Institute, Av. Vital Brasil, 1500, São Paulo 05503-900, BrazilLaboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilLaboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal 59010-180, BrazilThis study assesses the efficacy of different nanoemulsion formulations as new and innovative adjuvants for improving the in vivo immunization against the <i>Tityus serrulatus</i> scorpion venom. Nanoemulsions were designed testing key-variables such as surfactants, co-solvents, and the influence of the temperature, which would be able to induce the phase transition from a liquid crystal to a stable nanoemulsion, assessed for four months. Additionally, cationic-covered nanoemulsion with hyper-branched poly(ethyleneimine) was prepared and its performance was compared to the non-cationic ones. The physicochemical properties of the selected nanoemulsions and the interactions among their involved formulation compounds were carefully monitored. The cytotoxicity studies in murine macrophages (RAW 264.7) and red blood cells were used to compare different formulations. Moreover, the performance of the nanoemulsion systems as biocompatible adjuvants was evaluated using mice immunization protocol. The FTIR shifts and the zeta potential changes (from −18.3 ± 1.0 to + 8.4 ± 1.4) corroborated with the expected supramolecular anchoring of venom proteins on the surface of the nanoemulsion droplets. Cell culture assays demonstrated the non-toxicity of the formulations at concentrations less than 1.0 mg/mL, which were able to inhibit the hemolytic effect of the scorpion venom. The cationic-covered nanoemulsion has shown superior adjuvant activity, revealing the highest IgG titer in the immunized animals compared to both the non-cationic counterpart and the traditional aluminum adjuvant. In this approach, we demonstrate the incredible potential application of nanoemulsions as adjuvants, using a nanotechnology platform for antigen delivery system on immune cells. Additionally, the functionalization with hyper-branched poly(ethyleneimine) enhances this recognition and improves its action in immunization.https://www.mdpi.com/1999-4923/12/10/927<i>Tityus serrulatus</i> antiserumnanoemulsion adjuvantliquid crystalphase transitionsurface functionalizationimmunoadjuvant
spellingShingle Arthur Sérgio Avelino de Medeiros
Manoela Torres-Rêgo
Ariane Ferreira Lacerda
Hugo Alexandre Oliveira Rocha
Eryvaldo Sócrates Tabosa do Egito
Alianda Maira Cornélio
Denise V. Tambourgi
Matheus de Freitas Fernandes-Pedrosa
Arnóbio Antônio da Silva-Júnior
Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
Pharmaceutics
<i>Tityus serrulatus</i> antiserum
nanoemulsion adjuvant
liquid crystal
phase transition
surface functionalization
immunoadjuvant
title Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
title_full Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
title_fullStr Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
title_full_unstemmed Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
title_short Self-Assembled Cationic-Covered Nanoemulsion as A Novel Biocompatible Immunoadjuvant for Antiserum Production Against <i>Tityus serrulatus</i> Scorpion Venom
title_sort self assembled cationic covered nanoemulsion as a novel biocompatible immunoadjuvant for antiserum production against i tityus serrulatus i scorpion venom
topic <i>Tityus serrulatus</i> antiserum
nanoemulsion adjuvant
liquid crystal
phase transition
surface functionalization
immunoadjuvant
url https://www.mdpi.com/1999-4923/12/10/927
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