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Open AccessArticle

Development of Kaempferol-Loaded Gelatin Nanoparticles for the Treatment of Corneal Neovascularization in Mice

1
Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
2
Department of Chemical Engineering and Biotechnology, National Taipei University of Technology, Taipei 10608, Taiwan
3
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli County 35053, Taiwan
4
International Ph.D. Program for Cell Therapy and Regeneration Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
5
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
6
Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
7
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia
8
Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC 3002, Australia
9
International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
10
Research Center of Biomedical Device, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(12), 635; https://doi.org/10.3390/pharmaceutics11120635
Received: 30 September 2019 / Revised: 10 November 2019 / Accepted: 14 November 2019 / Published: 28 November 2019
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)
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. View Full-Text
Keywords: gelatin nanoparticles; kaempferol; corneal neovascularization; anti-angiogenesis; human umbilical vascular endothelial cells (HUVECs) gelatin nanoparticles; kaempferol; corneal neovascularization; anti-angiogenesis; human umbilical vascular endothelial cells (HUVECs)
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MDPI and ACS Style

Chuang, Y.-L.; Fang, H.-W.; Ajitsaria, A.; Chen, K.-H.; Su, C.-Y.; Liu, G.-S.; Tseng, C.-L. Development of Kaempferol-Loaded Gelatin Nanoparticles for the Treatment of Corneal Neovascularization in Mice. Pharmaceutics 2019, 11, 635.

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