Chemical Biology Unit, Institute of Nano Science and Technology, Knowledge City, SAS Nagar, Punjab 140306, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Punjab 160062, India.
Mater Sci Eng C Mater Biol Appl. 2021 May;124:112038. doi: 10.1016/j.msec.2021.112038. Epub 2021 Mar 20.
Inflammatory Bowel Disease (IBD) is a complex inflammatory condition arising due to interactions of environmental and genetic factors that lead to dysregulated immune response and inflammation in intestine. Complementary and alternative medicine approaches have been utilized to treat IBD. However, chronic inflammatory diseases are not medically curable. Hence, potent anti-inflammatory therapeutic agents are urgently warranted. Melatonin has emerged as a potent anti-inflammatory and neuroprotective candidate. Although, it's therapeutic efficacy is compromised due to less solubility and rapid clearance. Hence, we have synthesized melatonin loaded chitosan nanoparticle (Mel-CSNPs) to improve drug release profile and evaluate its in-vitro and in-vivo therapeutic efficacy. Mel-CSNPs exhibited better anti-inflammatory response in an in-vitro and in-vivo IBD model. Significant anti-inflammatory activity of Mel-CSNPs is attributed to nitric oxide (NO) reduction, inhibited nuclear translocation of NF-kB p65 and reduced IL-1β and IL-6 expression. In-vivo biodistribution study has shown a good distribution profile. Effective in-vivo therapeutic efficiency of Mel-CSNPs has been confirmed with reduced disease activity index parameters and inhibited neutrophilic infiltration. Histological evaluation has further proved the protective effect of Mel-CSNPs by preventing crypt damage and immune cells infiltration against Dextran Sodium Sulphate induced insults. Immuno-histochemical analysis has confirmed anti-inflammatory action of Mel-CSNPs with reduction of inflammatory markers, Nitric Oxide Synthase-2 (NOS2) and Nitro-tyrosine. Indeed, this study divulges anti-inflammatory activity of Mel-CSNPs by improving the therapeutic potential of melatonin.
炎症性肠病（IBD）是一种复杂的炎症性疾病，由于环境和遗传因素的相互作用导致肠道免疫反应和炎症失调而发生。补充和替代医学方法已被用于治疗 IBD。然而，慢性炎症性疾病无法通过医学治愈。因此，迫切需要有效的抗炎治疗药物。褪黑素已成为一种有效的抗炎和神经保护候选药物。然而，由于溶解度低和清除速度快，其治疗效果受到影响。因此，我们合成了负载褪黑素的壳聚糖纳米粒子（Mel-CSNPs），以改善药物释放特性并评估其体外和体内治疗效果。Mel-CSNPs 在体外和体内 IBD 模型中表现出更好的抗炎反应。Mel-CSNPs 的显著抗炎活性归因于一氧化氮（NO）的减少、抑制核转位的 NF-kB p65 以及减少白细胞介素-1β和白细胞介素-6 的表达。体内生物分布研究显示出良好的分布特征。Mel-CSNPs 的有效体内治疗效果已通过降低疾病活动指数参数和抑制中性粒细胞浸润得到证实。组织学评估进一步通过防止隐窝损伤和免疫细胞浸润来证实 Mel-CSNPs 的保护作用，以对抗葡聚糖硫酸钠诱导的损伤。免疫组织化学分析证实了 Mel-CSNPs 的抗炎作用，降低了炎症标志物、一氧化氮合酶-2（NOS2）和硝基酪氨酸的表达。事实上，这项研究通过提高褪黑素的治疗潜力揭示了 Mel-CSNPs 的抗炎活性。
