Ferreira Luana Mota, Sari Marcel Henrique Marcondes, Cervi Verônica Ferrari, Gehrcke Mailine, Barbieri Allanna Valentini, Zborowski Vanessa Angonesi, Beck Ruy Carlos Ruver, Nogueira Cristina Wayne, Cruz Letícia
Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Programa de Pós-Graduação em Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil.
Colloids Surf B Biointerfaces. 2016 Aug 1;144:214-221. doi: 10.1016/j.colsurfb.2016.04.008. Epub 2016 Apr 5.
The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested.
根据扭体试验和完全弗氏佐剂诱导的小鼠爪部炎症，评估了纳米乳剂中石榴籽油与酮洛芬的组合，以提高其镇痛效果。这些制剂具有良好的特性，并提高了酮洛芬对紫外线C辐射暴露的光稳定性。透析袋技术表明，3小时后纳米乳剂中100%的药物被释放，油量对释放没有影响。此外，还获得了时间和剂量反应曲线，以确定制剂的镇痛效果。在试验后，含酮洛芬的纳米乳剂在时间反应曲线中显著减少了腹部收缩，显示出长达12小时的效果，而游离酮洛芬的效果长达3小时。此外，空白纳米乳剂在预处理1小时内腹部收缩有所减少。关于剂量反应曲线，游离酮洛芬在0.5mg/Kg剂量时有效果，纳米乳剂在1.0mg/Kg剂量时有效果。进行时间和剂量反应曲线以确定炎症性疼痛中的镇痛效果。在使用von Frey毛发进行机械性异常性疼痛测试评估后，游离酮洛芬的效果长达6小时，而纳米乳剂的效果长达10小时。此外，通过评估谷丙转氨酶（ALT）、谷草转氨酶（AST）活性和尿素水平进行了急性毒性试验。治疗7天后，未发现纳米乳剂有任何毒性作用。总之，在测试的动物模型中，负载酮洛芬的石榴籽油纳米乳剂具有良好的特性和高镇痛活性。
