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Anti-Inflammatory Polymeric Nanoparticles Based on Ketoprofen and Dexamethasone.
Pharmaceutics ( IF 5.4 ) Pub Date : 2020-07-31 , DOI: 10.3390/pharmaceutics12080723
Eva Espinosa-Cano 1, 2 , Maria Rosa Aguilar 1, 2 , Yadileiny Portilla 3 , Domingo F Barber 3 , Julio San Román 1, 2
Affiliation  

Polymeric nanoparticles that combine dexamethasone and naproxen reduce inflammation and synergistically inhibit Interleukin-12b (Il12b) transcription in macrophages. This effect can be the result of a cyclooxygenase-dependent or a cyclooxygenase-independent mechanism. The aim of this work is to obtain potent anti-inflammatory polymeric nanoparticles by the combination of dexamethasone and ketoprofen, one of the most efficient cyclooxygenase-inhibitors among non-steroidal anti-inflammatory drugs, with appropriate hydrodynamic properties to facilitate accumulation and co-release of drugs in inflamed tissue. Nanoparticles are spherical with hydrodynamic diameter (117 ± 1 nm), polydispersity (0.139 ± 0.004), and surface charge (+30 ± 1 mV), which confer them with high stability and facilitate both macrophage uptake and internalization pathways to favor their retention at the inflamed areas and lysosomal degradation and drug release, respectively. In vitro biological studies concluded that the dexamethasone-loaded ketoprofen-bearing system is non-cytotoxic and efficiently reduces lipopolysaccharide-induced nitric oxide release. The RT-qPCR analysis shows that the ketoprofen nanoparticles were able to reduce to almost basal levels the expression of tested pro-inflammatory markers and increase the gene expression of anti-inflammatory cytokines under inflammatory conditions. However, the synergistic inhibition of Il12b observed in nanoparticles that combine dexamethasone and naproxen was not observed in nanoparticles that combine dexamethasone and ketoprofen, suggesting that the synergistic trans-repression of Il12b observed in the first case was not mediated by cyclooxygenase-dependent pathways.

中文翻译:

基于酮洛芬和地塞米松的抗炎聚合物纳米颗粒。

地塞米松和萘普生结合的聚合物纳米颗粒可减轻炎症并协同抑制白介素12b(Il12b)在巨噬细胞中转录。该作用可能是依赖于环氧合酶或不依赖环氧合酶的机制的结果。这项工作的目的是通过地塞米松和酮洛芬(一种非甾体类抗炎药中最有效的环加氧酶抑制剂)的组合获得有效的抗炎聚合物纳米颗粒,并具有适当的流体动力学特性以促进积累和共释放在发炎的组织中的药物。纳米颗粒为球形,具有流体动力学直径(117±1 nm),多分散性(0.139±0.004)和表面电荷(+30±1 mV),这使它们具有较高的稳定性,并促进巨噬细胞的摄取和内在化途径,有利于其保留在发炎区域,溶酶体降解和药物释放。体外生物学研究得出的结论是,地塞米松负载酮洛芬的系统无细胞毒性,可有效降低脂多糖诱导的一氧化氮释放。RT-qPCR分析表明,酮洛芬纳米颗粒能够在炎性条件下将测试的促炎标记物的表达降低至几乎基础水平,并增加抗炎细胞因子的基因表达。但是,协同抑制 RT-qPCR分析表明,酮洛芬纳米颗粒能够在炎性条件下将测试的促炎标记物的表达降低至几乎基础水平,并增加抗炎细胞因子的基因表达。但是,协同抑制 RT-qPCR分析表明,酮洛芬纳米颗粒能够在炎性条件下将测试的促炎标记物的表达降低至几乎基础水平,并增加抗炎细胞因子的基因表达。但是,协同抑制在结合地塞米松和萘普生的纳米颗粒中观察到的Il12b在结合地塞米松和酮洛芬的纳米颗粒中未观察到,表明在第一种情况下观察到的Il12b的协同反式抑制不是由环氧合酶依赖性途径介导的。
更新日期:2020-07-31
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