Esculin-loaded nanoparticles ameliorate adjuvant-induced polyarthritis via subduing inflammatory and oxidative stress biomarkers in Wistar rats.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2024-12-28 DOI:10.1007/s10787-024-01621-w

Mehak Fatima, Ammara Saleem, Muhammad Furqan Akhtar, Kanwal Akhtar, Muhammad Imran Khan

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Abstract

Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed. ENPs were synthesized using the ion gelation method and their characterization was done. The formulated ENPs had a particle size of 205.1 nm, a polydispersity index of 0.574, zeta potential of 3.6 ± 0.1 mV, and entrapment efficiency of 68%, SEM analysis showed round spherical and irregularity from the outer surface, XRD revealed amorphous nature. Drug release from the carrier by erosion method. For anti-arthritic potential, 0.1 ml Complete Freund's Adjuvant was injected in the left hind paw of all Wistar rats except normal rats on day 1 and treatment with ENPS at 5, 10, 20, ESC and methotrexate (standard drug) was started at 8th day orally and continued for 21 days. Treatment with methotrexate, ESC, and ENPs revealed a significant reduction of paw edema and pain, restoration of body and immune organ weight, Treatment with ENPs 20 mg/kg remarkably (p < 0.0001) restored serotonin and noradrenaline level, oxidation status, hematological and biochemical parameters with significant down-regulation (p < 0.0001) of IL-6, COX-2, TNF-alpha, NF-κβ whereas, up-regulation of IL-4 and IL-10 in comparison to disease control group as obvious from histological examination of sciatic nerve, liver, and ankle joint. The LD₅₀ of ENPs was more than 2000 mg/kg in the acute toxicity study. The ENPs exhibited anti-inflammatory and anti-arthritic activities especially ENPs at 20 mg/kg.

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esculin负载纳米颗粒通过抑制Wistar大鼠炎症和氧化应激生物标志物改善佐剂诱导的多关节炎。

类风湿性关节炎是一种影响多个关节的自身免疫性疾病，需要终生治疗。本研究旨在制备壳聚糖纳米颗粒（ENPs）并评价其抗炎和抗关节炎作用。同时进行了ENPs的急性毒性研究。采用离子凝胶法制备了ENPs，并对其进行了表征。制备的ENPs粒径为205.1 nm，多分散性指数为0.574，zeta电位为3.6±0.1 mV，包封效率为68%，SEM分析显示为圆球状，外表面呈不规则状，XRD显示为无定形。药物通过腐蚀法从载体中释放。为了观察其抗关节炎作用，除正常大鼠外，所有Wistar大鼠于第1天左后爪注射完全弗氏佐剂0.1 ml，第8天开始口服ENPS， 5、10、20、ESC和甲氨蝶呤（标准药物），持续治疗21天。用甲氨蝶呤、ESC和ENPs治疗显示足跖水肿和疼痛明显减轻，身体和免疫器官重量恢复，用ENPs治疗20 mg/kg显著（急性毒性研究中ENPs的p50大于2000 mg/kg）。ENPs表现出抗炎和抗关节炎的活性，特别是在20 mg/kg时。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]