de Melo Nathalie Ferreira Silva, de Macedo Cristina Gomes, Bonfante Ricardo, Abdalla Henrique Ballassini, da Silva Camila Morais Gonçalves, Pasquoto Tatiane, de Lima Renata, Fraceto Leonardo Fernandes, Clemente-Napimoga Juliana Trindade, Napimoga Marcelo Henrique
Laboratory of Immunology and Molecular Biology, São Leopoldo Mandic Institute and Researcher Center, Campinas, Brazil.
Department of Environmental Engineering, São Paulo State University (UNESP), Sorocaba, Brazil.
PLoS One. 2016 Aug 30;11(8):e0161796. doi: 10.1371/journal.pone.0161796. eCollection 2016.
15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has physiological properties including pronounced anti-inflammatory activity, though it binds strongly to serum albumin. The use of solid lipid nanoparticles (SLN) can improve therapeutic properties increasing drug efficiency and availability. 15d-PGJ2-SLN was therefore developed and investigated in terms of its immunomodulatory potential. 15d-PGJ2-SLN and unloaded SLN were physicochemically characterized and experiments in vivo were performed. Animals were pretreated with 15d-PGJ2-SLN at concentrations of 3, 10 or 30 μg·kg-1 before inflammatory stimulus with carrageenan (Cg), lipopolysaccharide (LPS) or mBSA (immune response). Interleukins (IL-1β, IL-10 and IL-17) levels were also evaluated in exudates. The 15d-PGJ2-SLN system showed good colloidal parameters and encapsulation efficiency of 96%. The results showed that the formulation was stable for up to 120 days with low hemolytic effects. The 15d-PGJ2-SLN formulation was able to reduce neutrophil migration in three inflammation models tested using low concentrations of 15d-PGJ2. Additionally, 15d-PGJ2-SLN increased IL-10 levels and reduced IL-1β as well as IL-17 in peritoneal fluid. The new 15d-PGJ2-SLN formulation highlights perspectives of a potent anti-inflammatory system using low concentrations of 15d-PGJ2.
15-脱氧-Δ12,14-前列腺素J2（15d-PGJ2）是一种过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂，虽与血清白蛋白紧密结合，但具有包括显著抗炎活性在内的生理特性。使用固体脂质纳米粒（SLN）可改善治疗特性，提高药物效率和利用率。因此，研发了15d-PGJ2-SLN并对其免疫调节潜力进行了研究。对15d-PGJ2-SLN和未负载的SLN进行了物理化学表征，并开展了体内实验。在用角叉菜胶（Cg）、脂多糖（LPS）或甲基化牛血清白蛋白（mBSA，免疫反应）进行炎症刺激前，用浓度为3、10或30μg·kg-1的15d-PGJ2-SLN对动物进行预处理。还评估了渗出液中的白细胞介素（IL-1β、IL-10和IL-17）水平。15d-PGJ2-SLN系统显示出良好的胶体参数，包封率为96%。结果表明，该制剂在长达120天内稳定，溶血作用低。15d-PGJ2-SLN制剂在使用低浓度15d-PGJ2测试的三种炎症模型中能够减少中性粒细胞迁移。此外，15d-PGJ2-SLN提高了腹膜液中IL-10水平，降低了IL-1β以及IL-17水平。新的15d-PGJ2-SLN制剂突出了使用低浓度15d-PGJ2的强效抗炎系统的前景。
