Non-clinical study of the anxiolytic effect of Citrus aurantium L. essential oil in an inclusion complex with 2-hydroxypropyl-β-cyclodextrin

Gabriel Chaves Neto; Humberto Hugo Nunes de  Andrade; João Euclides Fernandes  Braga; Lucindo José  Quintans Júnior; Reinaldo Nóbrega de  Almeida; Margareth de Fátima Formiga Melo  Diniz

Gabriel Chaves Neto Laboratório de Psicofarmacologia, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, PB, Brasil https://orcid.org/0000-0002-2872-3732
Humberto Hugo Nunes de Andrade Laboratório de Psicofarmacologia, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, PB, Brasil https://orcid.org/0000-0003-0377-7985
João Euclides Fernandes Braga Laboratório de Psicofarmacologia, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, PB, Brasil https://orcid.org/0000-0002-9242-5326
Lucindo José Quintans Júnior Departamento de Fisiologia (DFS), Universidade Federal de Sergipe, São Cristovão, SE, Brasil https://orcid.org/0000-0001-5155-938X
Reinaldo Nóbrega de Almeida Laboratório de Psicofarmacologia, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, PB, Brasil https://orcid.org/0000-0003-4430-8202
Margareth de Fátima Formiga Melo Diniz Laboratório de Psicofarmacologia, Instituto de Pesquisa em Fármacos e Medicamentos, Universidade Federal da Paraíba, João Pessoa, PB, Brasil https://orcid.org/0000-0001-9896-9044

Keywords: Anxiety, Volatile Oils, Citrus, Cyclodextrins, Pharmaceutical Technology

Abstract

Anxiety in the world population has increased significantly; the problem has encouraged studies regarding innovative alternatives for treatment. Research with Citrus aurantium L. essential oil (CEO) has revealed positive results with anxiolytic effects in both animals and humans. However, certain limitations affect its storage and preservation, its efficiency in therapy, and determination of adequate posologies. The potential use of cyclodextrins as drug carriers has been successfully explored. This study aims to assess the anxiolytic potential of a CEO/2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. Preparation of the inclusion complex was performed using the Alpha 1-2 LDplus lyophilizer. To allow formation, and avoid loss of volatiles to the atmosphere, Limonene (LIM), the main compound in CEO, together with HPβ-CD in a molar ratio of (1: 1M) was dispersed in ethanol for 36 hours using a laboratory shaker at room temperature (25°C). Non-clinical murine pharmacological tests were performed for anxiety assessment in experimental and control groups. To assess anxiety and motor impairment, the animals were evaluated using the elevated plus maze, open field, and rota-rod tests. Satisfactory results of the anxiolytic effect of the OEC complexed in HP-β-CD were observed, with the indication of an potentiation of the effect with doses lower than 500 mg/kg and 250 mg/kg complexed, suggesting improvement in the anxiolytic properties of the OEC.