Fabrication and efficacy evaluation of chloroquine nanoparticles in CFA-induced arthritic rats using TNF-α ELISA
Fabrication and efficacy evaluation of chloroquine nanoparticles in CFA-induced arthritic rats using TNF-α ELISA
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DOI：
10.1016/j.ejps.2016.01.009
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发表时间：
2016-03-10
影响因子：
4.6
通讯作者：
Madgulkar, Ashwini R.
中科院分区：
文献类型：
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作者：
Bhalekar, Mangesh R.;Upadhaya, Prashant G.;Madgulkar, Ashwini R.
类风湿性关节炎（RA）是一种慢性全身性自身免疫性疾病，它刺激各种免疫细胞，特别是巨噬细胞，引起各种促炎细胞因子如TNF-α的释放，导致持续性滑膜炎。氯喹，一种抗疟疾药物，抑制TNF-α的产生，从而阻止疾病的进展。本研究的目的是制备、表征和证明氯喹负载的固体脂质纳米粒（CQ-SLN）在关节炎大鼠中和降低TNF-α水平中的动力学和动态功效。采用熔融均质法制备CQ-SLN，并进行冻干。粒径、zeta电位、PDI和包封率分别为113.6 +/- 0.15 nm、-27.8 +/- 1.21 mV、0.125 +/- 0.03和93.45 +/- 0.43%。离体内吞摄取研究揭示了从肠道摄取SLN的内吞途径的占用。药代动力学评价的血浆药物特征显示药物的AUC、半衰期增加，消除率降低。药效学研究显示爪体积减小、骨侵蚀和软骨破坏，组织病理学研究也反映了这一点。TNF-α ELISA的结论是，在用CQ-SLN治疗后，滑液中的TNF-α水平显著降低，因此，得出CQ-SLN可用作降低关节炎部位的炎性TNF-α和阻止疾病进展的潜力的结论。(C)2016爱思唯尔B. V.保留所有权利。
Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, stimulates various immune cells especially macrophages, causing release of various proinflammatory cytokines such as TNF-alpha leading to persistent synovitis. Chloroquine, an anti-malarial drug inhibits the production of TNF-alpha, thus, halting the disease progression. The aim of the present study was fabrication, characterization and demonstration of kinetic and dynamic efficacy of chloroquine loaded solid lipid nanoparticles (CQ-SLNs) in arthritic rats and in lowering TNF-alpha levels. CQ-SLNs were prepared using melt homogenization method and subjected to lyophilization. The particle size, zeta potential, PDI and entrapment efficiency were found to be 113.6 +/- 0.15 nm, -27.8 +/- 1.21 mV, 0.125 +/- 0.03 and 93.45 +/- 0.43% respectively. Ex vivo endocytic uptake studies revealed engrossment of endocytic pathways in the uptake of SLN from intestine. Plasma drug profile upon pharmacokinetic evaluation demonstrated increased AUC, half-life and decreased elimination rate of the drug. Pharmacodynamic studies revealed reduction in the paw volume, bone erosion and cartilage destruction, the same was also reflected in histopathological studies. The TNF-alpha ELISA concluded that the TNF-alpha level was significantly reduced in the synovial fluid upon treatment with CQ-SLN, thus, leading to the conclusion that CQ-SLN could be used as a potential in reducing inflammatory TNF-alpha at the arthritic site and halting the disease progression. (C) 2016 Elsevier B.V. All rights reserved.