Souza Rafael Limongi de, Opretzka Luíza Carolina França, Morais Mayara Castro de, Melo Camila de Oliveira, Oliveira Brunna Emanuelly Guedes de, Sousa Damião Pergentino de, Villarreal Cristiane Flora, Oliveira Elquio Eleamen
Laboratory of Synthesis and Drug Delivery, State University of Paraíba, Rua Horácio Trajano, SN, João Pessoa 58071-160, PB, Brazil.
Laboratório de Farmacologia e Terapêutica Experimental, Faculdade de Farmácia, Universidade Federal da Bahia, Rua Barão de Jeremoabo, 147, Ondina, Salvador 40170-115, BA, Brazil.
Pharmaceuticals (Basel). 2023 Dec 21;17(1):17. doi: 10.3390/ph17010017.
Carvacryl acetate (CA) is a monoterpene obtained from carvacrol, which exhibits anti-inflammatory activity. However, its low solubility in aqueous media limits its application and bioavailability. Herein, we aimed to develop a carvacryl acetate nanoemulsion (CANE) and assess its anti-inflammatory potential in preclinical trials. The optimized nanoemulsion was produced by ultrasound, and stability parameters were characterized for 90 days using dynamic light scattering after hydrophilic-lipophilic balance (HLB) assessment. To evaluate anti-inflammatory activity, a complete Freund's adjuvant-induced inflammation model was established. Paw edema was measured, and local interleukin (IL)-1β levels were quantified using ELISA. Toxicity was assessed based on behavioral changes and biochemical assays. The optimized nanoemulsion contained 3% CA, 9% surfactants (HLB 9), and 88% water and exhibited good stability over 90 days, with no signs of toxicity. The release study revealed that CANE followed zero-order kinetics. Dose-response curves for CA were generated for intraperitoneal and oral administration, demonstrating anti-inflammatory effects by both routes; however, efficacy was lower when administered orally. Furthermore, CANE showed improved anti-inflammatory activity when compared with free oil, particularly when administered orally. Moreover, daily treatment with CANE did not induce behavioral or biochemical alterations. Overall, these findings indicate that nanoemulsification can enhance the anti-inflammatory properties of CA by oral administration.
乙酸香芹酯（CA）是一种从香芹酚中提取的单萜，具有抗炎活性。然而，其在水性介质中的低溶解度限制了其应用和生物利用度。在此，我们旨在开发一种乙酸香芹酯纳米乳剂（CANE），并在临床前试验中评估其抗炎潜力。通过超声制备优化的纳米乳剂，并在亲水亲油平衡（HLB）评估后使用动态光散射对稳定性参数进行90天的表征。为了评估抗炎活性，建立了完全弗氏佐剂诱导的炎症模型。测量爪部水肿，并使用酶联免疫吸附测定（ELISA）对局部白细胞介素（IL）-1β水平进行定量。基于行为变化和生化分析评估毒性。优化的纳米乳剂含有3%的CA、9%的表面活性剂（HLB 9）和88%的水，在90天内表现出良好的稳定性，且无毒性迹象。释放研究表明CANE遵循零级动力学。生成了腹腔注射和口服给药的CA剂量反应曲线，表明两种给药途径均具有抗炎作用；然而，口服给药时疗效较低。此外，与游离油相比，CANE表现出更好的抗炎活性，尤其是口服给药时。而且，每天用CANE治疗不会引起行为或生化改变。总体而言，这些发现表明纳米乳化可以通过口服给药增强CA的抗炎特性。
