Development, characterization and evidence of anti-endometriotic activity of Phytocannabinoid-Rich nanoemulsions.

Autor: Nogueira Barradas T; Departamento de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Juiz de Fora (UFJF), R. José Lourenço Kelmer, s/n, Juiz de Fora, Zip Code: 36036-900, Brazil. Electronic address: thais.barradas@ufjf.br., Araujo Cardoso S; Programa de Pós-Graduação em Ciência e Tecnologia de Polímeros, Instituto de Macromoléculas. Universidade Federal do Rio de Janeiro (UFRJ), Avenida Carlos Chagas Filho, 373, Cidade Universitária, Ilha do Fundão, Rio de Janeiro Zip Code: 21941-902, Brazil., de Castro Grimaldi P; Instituto Federal do Rio de Janeiro (IFRJ), Rua Senador Furtado, n° 121/125, Maracanã, Rio de Janeiro Zip Code: 20260-100, Brazil., Lohan-Codeço M; Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro (UFRJ), Rua César Pernetta, 1766 (LS.3.01), Cidade Universitária, Ilha do Fundão, Rio de Janeiro Zip Code: 21941-902, Brazil., Escorsim Machado D; Laboratório de Pesquisa em Ciências Farmacêuticas (LAPESF), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brasil., Medina de Mattos R; Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro (UFRJ), Rua César Pernetta, 1766 (LS.3.01), Cidade Universitária, Ilha do Fundão, Rio de Janeiro Zip Code: 21941-902, Brazil., Eurico Nasciutti L; Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro (UFRJ), Rua César Pernetta, 1766 (LS.3.01), Cidade Universitária, Ilha do Fundão, Rio de Janeiro Zip Code: 21941-902, Brazil., Palumbo A Jr; Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Universidade Federal do Rio de Janeiro (UFRJ), Rua César Pernetta, 1766 (LS.3.01), Cidade Universitária, Ilha do Fundão, Rio de Janeiro Zip Code: 21941-902, Brazil.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Aug 25; Vol. 643, pp. 123049. Date of Electronic Publication: 2023 May 15.
DOI: 10.1016/j.ijpharm.2023.123049
Abstrakt: During the last decades, the cannabinoid research for therapeutic purposes has been rapidly advancing, with an ever-growing body of evidence of beneficial effects for a wide sort of conditions, including those related to mucosal and epithelial homeostasis, inflammatory processes, immune responses, nociception, and modulating cell differentiation. β-caryophyllene (BCP) is a lipophilic volatile sesquiterpene, known as non-cannabis-derived phytocannabinoid, with documented anti-inflammatory, anti-proliferative and analgesic effects in both in vitro and in vivo models. Copaiba oil (COPA) is an oil-resin, mainly composed of BCP and other lipophilic and volatile components. COPA is reported to show several therapeutic effects, including anti-endometriotic properties and its use is widespread throughout the Amazonian folk medicine. COPA was nanoencapsulated into nanoemulsions (NE), then evaluated regarding the potential for transvaginal drug delivery and providing endometrial stromal cell proliferation in vitro. Transmission electron microscopy (TEM) showed that spherical NE were obtained with COPA concentration that varied from 5 to 7 wt%, while surfactant was maintained at 7.75 wt%. Dynamic light scattering (DLS) measurements showed droplet sizes of 30.03 ± 1.18, 35.47 ± 2.02, 43.98 ± 4.23 and PdI of 0.189, 0.175 and 0.182, respectively, with stability against coalescence and Ostwald ripening during 90 days. Physicochemical characterization results suggest that NE were able to both improve solubility and loading capacity, and increase thermal stability of COPA volatile components. Moreover, they showed slow and sustained release for up to eight hours, following the Higuchi kinetic model. Endometrial stromal cells from non-endometriotic lesions and ectopic endometrium were treated with different concentrations of COPA-loaded NE for 48 h to evaluate its effect on cell viability and morphology. The results suggested significant decrease in cell viability and morphological modifications in concentrations higher than 150 μg/ml of COPA-loaded NE, but not when cells were treated with the vehicle (without COPA). Given the relevance of Copaifera spp. species in folk medicine and their bio economical importance in the Amazon, the development of novel formulations to overcome the technological limitations related to BCP and COPA, is promising. Our results showed that COPA-loaded NE can lead to a novel, uterus-targeting, more effective and promising natural alternative treatment of endometriosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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