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柚皮素载多功能纳米粒增强肝纤维化的化疗疗效。

Naringenin loaded multifunctional nanoparticles to enhance the chemotherapeutic efficacy in hepatic fibrosis.

机构信息

Department of Clinical Nutrition, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, 650032, Yunnan, China.

Department of Clinical Laboratory, Affiliated Hospital of Dali University, Dali, 671000, China.

出版信息

Biomed Microdevices. 2020 Sep 21;22(4):68. doi: 10.1007/s10544-020-00524-1.

Abstract

Naringenin is highly potent dietary phenolic compound (Flavonoids) found as a major bioactive in citrus fruits. The low solubility of Naringenin, decreases its availability at the site of action by hindering solubility and transportation across the biological membrane. Naringenin loaded nanoparticles enhance the solubility and drug availability at site of action. Naringenin solid lipid nanoparticles were prepared by emulsification and homogenization method using GMO (glycerylmonooleate) and TPGS (Tocopheryl polyethylene glycol succinate) as co-stabilizer. Physico-chemical characterization confirmed the particles were of nanometer size, smooth and spherical morphology. The FTIR and DSC studies conforms that drug and polymers are compatible. The in-vitro study shows prolong and sustained release of Naringenin upto 90 Hrs. In-vivo studies conforms the prolonged and efficient treatment of Hepatic fibrosis. The liver enzymes and pro inflammatory cytokines in blood got significantly reversed with the rats exposed to Naringenin nanoparticle indicating reduced liver damage and fibrosis. Nanoformulation enhances the bioavailability of Naringenin and liver specific delivery of the same, which up-regulates MMP-2 hepatic proteins resulting in reduced liver fibrosis.

摘要

柚皮素是一种高效的饮食类多酚化合物(类黄酮),主要存在于柑橘类水果中。柚皮素的低溶解度通过阻碍其在生物膜中的溶解度和转运,降低了其在作用部位的可用性。柚皮素负载纳米粒子可提高作用部位的溶解度和药物可用性。通过乳化和匀化法,使用 GMO(单硬脂酸甘油酯)和 TPGS(生育酚聚乙二醇琥珀酸酯)作为共稳定剂,制备柚皮素固体脂质纳米粒。物理化学特性分析证实了这些粒子具有纳米级大小、光滑和球形的形态。傅里叶变换红外光谱(FTIR)和差示扫描量热法(DSC)研究表明药物和聚合物是相容的。体外研究表明,柚皮素的释放可以延长至 90 小时以上。体内研究表明,柚皮素纳米粒子可延长和有效治疗肝纤维化。与暴露于柚皮素纳米粒子的大鼠的血液中的肝酶和促炎细胞因子相比,这些指标得到了显著逆转,这表明肝损伤和纤维化减少。纳米制剂提高了柚皮素的生物利用度,并实现了其在肝脏的靶向递送,从而上调 MMP-2 肝蛋白,减少肝纤维化。

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