Development of Kaempferol-loaded gelatin nanoparticles for the treatment of corneal neovascularization in mice

Yu Lun Chuang, Hsu Wei Fang, Aditya Ajitsaria, Ko Hua Chen, Chen Ying Su, Guei Sheung Liu, Ching Li Tseng

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Cornea is the transparent layer in front of the eye that does not contain blood vessels. Among eye diseases, corneal neovascularization (NV) is one of the major causes of vision loss, since it can also lead to blindness. An herbal extraction containing flavonoid, kaempferol (KA), with antiangiogenic effect was chosen as a candidate drug for inhibited vessel formation. The use of nanomedicine has led to higher drug bioavailability and slow release of the drug as an effective therapeutic formulation in ocular drug delivery. In this study, we prepared gelatin nanoparticles (GNP) with kaempferol encapsulation (GNP-KA) for corneal NV treatment by topical delivery, i.e., eye drops. We found that GNP with/without KA loading was in the size of 85−150 nm, and its zeta potential was around 22−26 mV. The KA entrapment rate of GNP-KA was around 90−98%, and the loading rate was about 4.6%. The TEM results clearly indicated the GNP-KA NPs to be round spheres. The in vitro test involved the adoption of human umbilical vein endothelial cells (HUVECs) for coculture with these nanoparticles. From WST-8 assay, and cell migration examinations, it was evident that GNP-KA had the capacity to inhibit the cell viability and function of HUVECs. The results from in vivo tests such as ocular vessels observation, hematoxylin & eosin (H&E) stain, and metalloproteinases (MMP)/vascular endothelial growth factor (VEGF) quantification revealed the mice’s eyes with corneal NV treated by eye drops containing GNP-KA once daily for 7 days had better therapeutic effects with less vessels in-growths in the cornea, compared to the KA solution group by reducing the production of MMP and VEGF in the cornea. Therefore, we expected to achieve a comfortable treatment with a simple method using nanomedicine (GNP-KA) as ophthalmological agent delivered as eye drops.

Original languageEnglish
Article number635
JournalPharmaceutics
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Anti-angiogenesis
  • Corneal neovascularization
  • Gelatin nanoparticles
  • Human umbilical vascular endothelial cells (HUVECs)
  • Kaempferol

ASJC Scopus subject areas

  • Pharmaceutical Science

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