以甘草酸二钾为载体的新型二氢杨梅素纳米胶束滴眼液对小鼠干眼的治疗效果  

Therapeutic efficacy of novel dipotassium glycyrrhizinate-based dihydromyricetin nanomicelle ophthalmic solution on dry eye in mouse

作　　者：李丁丁 李晓丹 陈涛 辛萌 LI Dingding;LI Xiaodan;CHEN Tao;XIN Meng(Yantai Affiliated Hospital of Binzhou Medical University,Yantai 264100,Shandong Province,China)

机构地区：[1]滨州医学院烟台附属医院,山东省烟台市264100

出　　处：《眼科新进展》2024年第12期943-949,共7页Recent Advances in Ophthalmology

基　　金：山东省医药卫生科技项目(编号:202307021104)。

摘　　要：目的制备一种以甘草酸二钾(DG)为载体的增溶型二氢杨梅素(DMY)纳米胶束滴眼液,并评价其对小鼠干眼的治疗效果。方法使用薄膜分散-水化超声法制备DMY纳米胶束滴眼液(DG-DMY),并检测其在室温下的粒径、电位、包封率、储存稳定性等理化性质。使用小鼠检测DG-DMY的眼安全性。建立小鼠干眼模型,将小鼠随机分为正常对照组(未行干预,正常小鼠)、PBS对照组(PBS干预,干眼模型小鼠)、HA治疗组[1 g·L^(-1)玻璃酸钠(HA)干预,干眼模型小鼠]、DG-DMY治疗组(DG-DMY干预,干眼模型小鼠),每组各10只。干预10 d后观察并记录各组小鼠角膜上皮荧光素钠染色情况与眼表泪液量;HE染色观察小鼠角膜上皮、角膜基质及内皮细胞形态变化;ELISA实验检测小鼠角膜白细胞介素(IL)-6、IL^(-1)β表达水平。结果DG-DMY胶束滴眼液为淡黄色、透明溶液,纳米胶束尺寸为(208.8±3.9)nm,多分散性指数为0.277,Zeta电位为-(17.6±1.42)mV,包封率及载药量为76.72%与10.21%,室温(25℃)及储存温度(4℃)下储存性质稳定。小鼠实验显示DG-DMY滴眼液具有良好的活体眼耐受性。治疗结果显示,PBS治疗组小鼠角膜仍有大片着色,HA治疗组角膜着色减少,DG-DMY治疗组角膜几乎无着色。正常对照组、PBS对照组、HA治疗组和DG-DMY治疗组泪液分泌量分别为(5.15±0.47)mm、(2.26±0.41)mm、(4.02±0.53)mm、(4.11±0.54)mm。组织病理学检测结果显示,PBS对照组小鼠角膜上皮及松散的胶原结构,基底层受损;HA治疗组和DG-DMY治疗组小鼠角膜均减轻了组织病理损伤,显示有正常的角膜上皮、角膜基质与正常的内皮组织。ELISA检测结果显示,正常对照组、PBS对照组、HA治疗组及DG-DMY治疗组IL-6表达水平分别为(22.98±0.69)ng·g^(-1)、(108.1±6.06)ng·g^(-1)、(56.79±4.87)ng·g^(-1)及(44.01±0.99)ng·g^(-1),IL^(-1)β表达水平分别为(27.97±2.74)ng·g^(-1)、(115.70±5.16)ng·g^(-1)、(50.36±1.56)ng·g^(-1)及(4Objective To prepare an ophthalmic solution of dihydromyricetin(DMY)based on dipotassium glycyrrhizinate(DG)nanomicelle solubilization(DG-DMY)and evaluate its effect on dry eyes of mice.Methods DG-DMY was prepared using the thin-film hydration method,and its micelle size,potential,encapsulation efficiency and storage stability at room temperature were tested.The ocular safety of DG-DMY was tested on mice.Dry eye models were built in mice,which were divided into normal control group(normal mice without intervention),PBS control group(dry eye mouse models,intervened by PBS),HA treatment group[dry eye mouse models,intervened by 1 g·L^(-1) hyaluronic acid(HA)]and DG-DMY treatment group(dry eye mouse models,intervened by DG-DMY),with 10 mice in each group.The fluorescein sodium staining of corneal epithelium and surface tear secretion were recorded after 10 days of intervention.Morphological changes in corneal epithelium,corneal stroma and endothelial cells were monitored by hematoxylin&eosin staining.The enzyme-linked immunosorbent assay(ELISA)was adopted to measure the expression levels of interleukin-6(IL-6)and interleukin-1β(IL^(-1)β).Results DG-DMY is a light yellow,transparent solution with a nanomicelle size of(208.8±3.9)nm,polydispersity index of 0.277,Zeta potential of-(17.6±1.42)mV,encapsulation efficiency of 76.72%,and drug loading efficiency of 10.21%.It is stable at room temperature(25℃)and storage temperature(4℃).The mouse studies showed that DG-DMY displayed good in vivo tolerance in mice eyes.The therapeutic results showed that mice in the PBS treatment group still had extensive corneal staining,mice in the HA treatment group had reduced corneal staining,and mice in the DG-DMY treatment group had almost no corneal staining.The tear secretion of mice in the normal control group,PBS control group,HA treatment group and DG-DMY treatment group was(5.15±0.47)mm,(2.26±0.41)mm,(4.02±0.53)mm,and(4.11±0.54)mm.The histopathological results showed that the corneal epithelium,loose collagen structure

关 键 词：干眼 抗炎 纳米药物 甘草酸二钾 二氢杨梅素 胶束 

分 类 号：R777[医药卫生—眼科]