Programa de Pós-Graduação em Bioquímica e Bioprospecção, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Pelotas, RS, Brazil.
Departamento de Patologia Animal, Faculdade de Veterinária, UFPel, Pelotas, RS, Brazil.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109742. doi: 10.1016/j.msec.2019.109742. Epub 2019 May 15.
This study aimed to develop nanocapsules containing ketoprofen using rose hip oil (Keto-NC) as oil core, and to evaluate their anti-inflammatory activity in acute and chronic ear edema models in mice. Physicochemical characterization, drug release, photostability and cytotoxicity assays were performed for the developed Keto-NC formulations and compared to ketoprofen-loaded nanocapsules using medium chain triglycerides as oil core (Keto-MCT-NC). Anti-inflammatory activity of orally delivered KP (Ketoprofen-free; 10 mg.kg) or Keto-NC (2.5; 5; 10 mg.kg) was assessed in mouse acute and chronic ear edema induced by croton oil (CO). Edema histological characteristics were determined by H&E stain, and redox parameters were analyzed in blood plasma and erythrocytes. Keto-MCT-NC and Keto-NC did not exhibit differences regarding physicochemical parameters, including size diameters, polydispersity index, pH, Ketoprofen content, and encapsulation efficiency. However, Keto-NC, which contains rose hip oil as lipid core, decreased drug photodegradation under UVC radiation when compared to Keto-MCT-NC. KP or Keto-NC were not cytotoxic to keratinocyte cultures and produced equal edema inhibition in the acute protocol. Conversely, in the chronic protocol, Keto-NC was more effective in reducing edema (60-70% on 7-9th days of treatment) when compared to KP (40% on 8-9th days of treatment). This result was confirmed by histological analysis, which indicated reduction of edema and inflammatory infiltrate. A sub-therapeutic dose of Keto-NC (5 mg.kg) significantly reduced edema when compared to control. Finally, KP and Keto-NC exhibited similar effects on redox parameters, suggesting that the advantages associated with Ketoprofen nanoencapsulation did not involve oxidative stress pathways. The results showed that Keto-NC was more efficient than KP in reducing chronic inflammation. These data may be important for the development of strategies aiming treatment of chronic inflammatory diseases with fewer adverse effects.
本研究旨在开发含有酮洛芬的纳米胶囊，使用玫瑰果油（Keto-NC）作为油芯，并在急性和慢性耳水肿模型中评估其抗炎活性。对所开发的 Keto-NC 制剂进行了理化特性表征、药物释放、光稳定性和细胞毒性测定，并与使用中链甘油三酯作为油芯的载有酮洛芬的纳米胶囊（Keto-MCT-NC）进行了比较。通过涂抹克罗顿油（CO），在急性和慢性耳水肿模型中，评估了经口给予 KP（无酮洛芬；10mg.kg）或 Keto-NC（2.5、5、10mg.kg）的抗炎活性。通过 H&E 染色确定水肿的组织学特征，并分析血浆和红细胞中的氧化还原参数。Keto-MCT-NC 和 Keto-NC 在理化参数方面没有差异，包括粒径、多分散指数、pH 值、酮洛芬含量和包封效率。然而，与 Keto-MCT-NC 相比，含有玫瑰果油作为脂质核的 Keto-NC 减少了药物在 UVC 辐射下的光降解。与 KP 相比，KP 或 Keto-NC 对角质形成细胞培养物没有细胞毒性，并且在急性方案中产生了相等的水肿抑制作用。相反，在慢性方案中，与 KP 相比（治疗的第 8-9 天约为 40%），Keto-NC 在第 7-9 天的治疗中更有效地减轻水肿（约 60-70%）。组织学分析证实了这一结果，表明水肿和炎症浸润减少。Keto-NC 的亚治疗剂量（5mg.kg）与对照相比显著减少了水肿。最后，KP 和 Keto-NC 对氧化还原参数表现出相似的影响，这表明酮洛芬纳米封装的优势不涉及氧化应激途径。结果表明，Keto-NC 在减轻慢性炎症方面比 KP 更有效。这些数据对于开发旨在治疗慢性炎症性疾病的策略可能很重要，这些策略的副作用更少。
