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氨基纤维素接枝-聚己内酯包裹明胶纳米粒缓解类风湿关节炎炎症:一种联合治疗方法。

Aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles alleviate inflammation in rheumatoid arthritis: A combinational therapeutic approach.

机构信息

Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab, 160062, India.

Department of Biology, College of Sciences and Humanities, Prince Sattam bin Abdulaziz University, PO Box - 173, Alkharj, 11942, Saudi Arabia.

出版信息

Carbohydr Polym. 2021 Apr 15;258:117600. doi: 10.1016/j.carbpol.2020.117600. Epub 2021 Jan 12.

DOI:10.1016/j.carbpol.2020.117600
PMID:33593531
Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder and serious cause of disability. Despite considerable advances in RA management, challenges like extensive drug metabolism and rapid clearance causes poor bioavailability. Core-shell nanocarriers for co-delivery of glycyrrhizic acid (GA) and budesonide against RA were developed. GA-loaded gelatin nanoparticles (NPs) were synthesized and coated with budesonide encapsulated aminocellulose-grafted polycaprolactone (PCL-AC). GA- and budesonide-loaded PCL-AC-gel NPs had diameter of 200-225 nm. Dual drug-loaded (DDL) NPs reduced joint swelling and erythema in rats while markedly ameliorating bone erosion evidenced by radiological analysis, suppressed collagen destruction, restored synovial tissue, bone and cartilage histoarchitecture with reduced inflammatory cells infiltration. NPs also reduced various inflammatory biomarkers such as TNF-α, IL-1β, COX-2, iNOS. Results of this study suggest that dual NPs exerted superior therapeutic effects in RA compared to free drugs which may be attributed to slow and sustained drug release and NPs' ability to inhibit inflammatory mediators.

摘要

类风湿性关节炎(RA)是一种慢性自身免疫性疾病,也是导致残疾的严重原因。尽管 RA 管理取得了相当大的进展,但由于药物代谢广泛和清除迅速导致生物利用度差等挑战依然存在。本研究开发了用于同时递送甘草酸(GA)和布地奈德治疗 RA 的核壳纳米载体。合成了载 GA 的明胶纳米颗粒(NPs),并用包封布地奈德的氨基纤维素接枝聚己内酯(PCL-AC)进行包覆。GA 和布地奈德载 PCL-AC-明胶 NPs 的直径为 200-225nm。双载药(DDL)纳米粒减轻了大鼠的关节肿胀和红斑,放射学分析表明明显改善了骨侵蚀,抑制了胶原破坏,恢复了滑膜组织、骨和软骨的组织形态,减少了炎症细胞浸润。纳米粒还降低了各种炎症生物标志物,如 TNF-α、IL-1β、COX-2、iNOS。这项研究的结果表明,与游离药物相比,双载药纳米粒在 RA 中发挥了更好的治疗效果,这可能归因于缓慢和持续的药物释放以及纳米粒抑制炎症介质的能力。

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