Villa-Hermosilla Monica-Carolina, Fernández-Carballido Ana, Hurtado Carolina, Barcia Emilia, Montejo Consuelo, Alonso Mario, Negro Sofia
Department of Pharmaceutics and Food Technology, School of Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
Institute of Industrial Pharmacy, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
Pharmaceutics. 2021 Jun 24;13(7):951. doi: 10.3390/pharmaceutics13070951.
Rheumatoid arthritis (RA) is a chronic inflammatory disease with sulfasalazine (SSZ) extensively used for long-term treatment of both juvenile and adult RA. Its use is associated with adverse effects and toxicity due to its non-selective biodistribution. Macrophages play an important role in inflammatory processes. In order to target SSZ to macrophages in this work two microparticulate systems (MPs) are developed: SSZ-loaded PLGA MPs without and with α-tocopherol, with particle sizes lower than 5 μm and encapsulation efficiencies of 81.07 ± 11% and 63.50 ± 6.62%, respectively. Release of SSZ from MPs prepared with α-tocopherol was prolonged for 20 days. In RAW 264.7 cell macrophages MPs prepared with α-tocopherol were captured faster. Cell viability studies confirmed that SSZ-loaded MPs prepared without and with α-tocopherol did not produce cytotoxicity at the concentrations assayed. The anti-inflammatory activity of SSZ-loaded MPs was studied by quantifying interleukins IL-1, IL-6 and TNF-α in macrophages. All formulations produced a significant reduction of cytokine concentrations after 24 and 72 h, indicating that release of SSZ from the MPs was able to inhibit the inflammatory response induced by lipopolysaccharide (LPS). Gene expression of IL-1, IL-6 and TNF-α was decreased by SSZ-loaded MPs. SSZ-loaded MPs prepared with α-tocopherol will potentially allow increasing the residence time of SSZ in the synovial cavity, prolonging its duration of action, and reducing the adverse effects associated with its non-selective biodistribution.
类风湿性关节炎(RA)是一种慢性炎症性疾病,柳氮磺胺吡啶(SSZ)被广泛用于青少年和成人RA的长期治疗。由于其非选择性的生物分布,其使用与不良反应和毒性有关。巨噬细胞在炎症过程中起重要作用。为了在这项工作中将SSZ靶向巨噬细胞,开发了两种微粒系统(MPs):不含和含有α-生育酚的载SSZ聚乳酸-羟基乙酸共聚物(PLGA)MPs,粒径均小于5μm,包封率分别为81.07±11%和63.50±6.62%。用α-生育酚制备的MPs中SSZ的释放延长了20天。在RAW 264.7细胞巨噬细胞中,用α-生育酚制备的MPs被更快地捕获。细胞活力研究证实,不含和含有α-生育酚制备的载SSZ MPs在所测定的浓度下均未产生细胞毒性。通过定量巨噬细胞中的白细胞介素IL-1、IL-6和肿瘤坏死因子-α(TNF-α)研究了载SSZ MPs的抗炎活性。所有制剂在24小时和72小时后均使细胞因子浓度显著降低,表明MPs中SSZ的释放能够抑制脂多糖(LPS)诱导的炎症反应。载SSZ MPs降低了IL-1、IL-6和TNF-α的基因表达。用α-生育酚制备的载SSZ MPs可能会延长SSZ在滑膜腔中的停留时间,延长其作用持续时间,并减少与其非选择性生物分布相关的不良反应。