Aslam Bilal, Hussain Asif, Faisal Muhammad Naeem, Sindhu Zia-Ud-Din, Khan Rifat Ullah, Alhidary Ibrahim A, Naz Shabana, Tufarelli Vincenzo
Institute of Physiology and Pharmacology, University of Agriculture Faisalabad, Faisalabad 38040, Pakistan.
Department of Pharmacy, Riphah International University, Faisalabad 38000, Pakistan.
Biomedicines. 2023 Sep 28;11(10):2662. doi: 10.3390/biomedicines11102662.
This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound-polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund's adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly ( ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly ( ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably ( ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis.
本研究旨在评估姜黄素和美洛昔康共载聚乳酸-羟基乙酸共聚物（PLGA）纳米粒对佐剂性关节炎大鼠的抗关节炎活性。分别使用包裹姜黄素（nCur）、美洛昔康（nMlx）以及二者组合（nCur/Mlx）的PLGA纳米粒来表征zeta尺寸和电位、多分散指数、包封率（%）、化合物-聚合物相互作用（傅里叶变换红外光谱分析）以及表面形态（扫描电子显微镜成像）。在体内实验中，将完全弗氏佐剂诱导的关节炎大鼠连续28天腹腔注射姜黄素、美洛昔康、姜黄素加美洛昔康、nCur、nMlx和nCur/Mlx。结果显示，与游离化合物相比，nCur、nMlx和nCur/Mlx显著（≤0.05）减轻了爪肿胀和关节炎评分，恢复了体重以及免疫器官指数（胸腺和脾脏），还减轻了佐剂性关节炎大鼠血清中的炎症标志物（类风湿因子、C反应蛋白和前列腺素E2）以及氧化应激参数（丙二醛、超氧化物歧化酶和过氧化氢酶）。此外，单载和双载化合物的纳米粒显著（≤0.05）下调了促炎细胞因子（肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-6），上调了抗炎细胞因子（白细胞介素-4、白细胞介素-10和干扰素-γ），并调节了爪组织中骨保护素（OPG）和核因子κB受体活化因子配体（RANKL）的表达。上述结果通过放射学和组织病理学检查得到进一步证实。此外，与单独的nCur或nMlx相比，nCur/Mlx的抗关节炎作用显著（≤0.05）增强。总之，姜黄素的共纳米包封可以增强美洛昔康的抗关节炎活性，并可为制备用于治疗关节炎的纳米载体药物产品提供一种新的治疗方法。
