Therapeutic efficacy of novel dipotassium glycyrrhizinate-based dihydromyr-icetin nanomicelle ophthalmic solution on dry eye in mouse
10.13389/j.cnki.rao.2024.0178
- VernacularTitle: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
- Author:
Dingding LI
1
;
Xiaodan LI
;
Tao CHEN
;
Meng XIN
Author Information
1. 264100 山东省烟台市,滨州医学院烟台附属医院
- Keywords:
dry eye;
anti-inflammatory;
nanomedicine;
dipotassium glycyrrhizinate;
dihydromyricetin;
micelle
- From:
Recent Advances in Ophthalmology
2024;44(12):943-949
- CountryChina
- Language:Chinese
-
Abstract:
Objective To prepare an ophthalmic solution of dihydromyricetin(DMY)based on dipotassium glycyr-rhizinate(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 sta-bility 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-1β).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 and basal layer were damaged in the PBS control group;the corneal histopathological injury of mice in the HA treatment group and DG-DMY treatment group were mitigated,with normal corneal epithelium,corneal stroma and endothelial tissues.ELISA results showed that the expression level of IL-6 in the normal control group,PBS control group,HA treatment group and DG-DMY treatment group was(22.98±0.69)ng·g-1,(108.1±6.06)ng·g-1,(56.79±4.87)ng·g-1 and(44.01±0.99)ng·g-1,respectively,and the expression level of IL-1β was(27.97±2.74)ng·g-1,(115.70±5.16)ng·g-1,(50.36±1.56)ng·g-1 and(42.21±1.46)ng·g-1,respectively.Compared with the HA treatment group,the expression levels of IL-6 and IL-1β in the cornea of mice in the DG-DMY treatment group were lower,and the differences were statistically significant(both P＜0.05).Conclusion DG-DMY nano-preparation successfully prepared in this study is verified to act on benzalkonium chloride-induced dry eye effectively and control the inflammatory response of dry eye mouse models by inhibiting the expressions of IL-6 and IL-1β with high safety.
