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Item Poly-ε-caprolactone nanocapsules loaded with copaiba essential oil reduce inflammation and pain in mice.(2023) Pinto, Erveton Pinheiro; Costa, Sarah Olivia Alves Mendes da; D’Haese, Cecile; Nysten, Bernard; Machado, Francisco Paiva; Rocha, Leandro Machado; Souza, Tiago Marcolino de; Beloqui, Ana; Machado, Renes Resende; Araújo, Raquel SilvaDiverse drugs have been used for the management of inflammation disorders and pain. However, they present many side effects and stimulate the search for new pharmacotherapeutic alternatives. Plant-derived products such as copaiba essential oil (CO) offer beneficial pharmacological effects. On the other hand, essential oil’s low water solubility and physical instability hinder its in vivo application. Thus, poly-ε-caprolactone (PCL)-based nanocarriers have been used to increase their stability and efficacy. This work aimed to encapsulate CO in PCL nanocapsules and evaluate their effect on inflammation models and pain. The polymeric nanocapsules loading CO (CO-NC) were prepared by nanoprecipitation technique, characterized, and analyzed for their anti- inflammatory effect in vitro and in vivo. The results showed that CO-NC presented a spherical shape, 229.3 ± 1.5 nm diameter, and a negative zeta potential (approximately − 23 mV). CO and CO-NC presented anti- inflammatory and antioxidant effects by LPS-activated macrophages (J774 cells). In addition, CO-NC signifi- cantly reduced TNF-α secretion (3-fold) compared to CO. In vivo, pre-treatment with CO or CO-NC (50, 100, 200 mg/kg, intraperitoneal; i.p) reduced the mechanical allodynia, paw edema, and pro-inflammatory cytokines induced by intraplantar (i.pl) injection of carrageenan in mice. Specifically, CO-NC (200 mg/kg; i.p.) reduced the production of TNF-α similar to the control group. Our results support using polymeric nanocapsules for CO delivery in inflammatory conditions.