在这里,我们评估了美洛昔康和姜黄素共同包裹的PLGA纳米颗粒在实验性急性发热模型中的体内作用,伤害性感受,和炎症。7组(n=6)设计用于每个调查和预处理腹膜内(i.p.):对照组,美洛昔康(4mg/kgb.w.),姜黄素(15mg/kgb.w.),和含有PLGA覆盖的美洛昔康(Mlx-NP)和姜黄素(Cur-NP)单独和组合(Mlx-Cur-NP;在两个剂量下)的纳米颗粒的相等含量。结果表明,PLGA封装显着(p≤0.05)提高了每种化合物的体内活性。此外,美洛昔康和姜黄素的共包封增强了对酵母诱导的发热大鼠的解热作用,福尔马林和热致大鼠伤害性感受的抗伤害性作用,对二甲苯诱导的大鼠耳部水肿的抗水肿活性呈剂量依赖性。在角叉菜胶诱导的大鼠爪炎症中,美洛昔康和姜黄素共同负载(Mlx-Cur-NP)导致显著(p≤0.05)抑制爪炎症,降低TNF-α和PGE2水平,下调促炎细胞因子(TNF-α,IL-1β,和IL-6),以及爪组织中组织病理学变化和TNF-α免疫表达的降低。此外,与游离化合物和负载单化合物的纳米颗粒相比,Mlx-Cur-NP表现出显著的药理作用增强。因此,在可生物降解的纳米载体系统中,美洛昔康与姜黄素的联合可以提供有前途的解热,抗伤害性,和急性病症的抗炎治疗方法。
Herein, we evaluated the in vivo effects of meloxicam and curcumin co-encapsulated PLGA nanoparticles in experimental acute models of pyrexia, nociception, and inflammation. Seven groups (n = 6) were designed for each investigation and pretreated intraperitoneally (i.p.): the control group, meloxicam (4 mg/kg b.w.), curcumin (15 mg/kg b.w.), and equivalent content containing PLGA capped nanoparticles of meloxicam (Mlx-NP) and curcumin (Cur-NP) alone and in combination (Mlx-Cur-NP; at two doses). The results showed that PLGA encapsulation significantly (p ≤ 0.05) improved the in vivo activities of each compound. Furthermore, co-encapsulation of meloxicam and curcumin potentiated the anti-pyretic effect on yeast-induced pyretic rats, anti-nociceptive effect on nociception induced in rats by formalin and heat, and anti-edematogenic activity in xylene-induced ear edema in rats in a dose-dependent manner. In carrageenan-induced paw inflammation in rats, meloxicam and curcumin co-loading (Mlx-Cur-NP) resulted in significant (p ≤ 0.05) inhibition of paw inflammation, reduction in TNF-α and PGE2 levels, downregulation of expressions of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), as well as a decrease in histopathological changes and TNF-α immunoexpression in paw tissues. Moreover, Mlx-Cur-NP demonstrated noteworthy potentiation in pharmacological effects compared to free compounds and mono-compound-loaded nanoparticles. Thus, the association of meloxicam with curcumin in a biodegradable nanocarrier system could provide a promising anti-pyretic, anti-nociceptive, and anti-inflammatory therapeutic approach for acute conditions.