The normal cornea is transparent and avascular. Neovascularization of the cornea can disrupt visual function causing graft failure and blindness. In Taiwan, myopia is the most common eye disorder, the rate of myopia has soared to 86 % for youth. Most of them wear contact lenses usually causing cornea hypoxia which is high risk for developing corneal NV. Therefore, the public health impact of treatment cornea neovascularization is significant. The most common dosage for ophthalmic delivery is eye-drop formulation, but only 5 % of the administered dose retained in the ocular tissue after five min. The role of the ophthalmology care is focused on raising drug bioavailability in ocular tissue now. Although intraocular injection can highly increase drug concentration in ocular tissue, but repeat injection could lead to sever ocular diseases such as cataract or retinal detachment. To solve low dosage in ocular part, one way is using nanoparticles with therapeutic agent, nanomedicine, for treat various ocular diseases. Due to small sizes, they can improve bioavailability of therapeutic agents and pass through biological barriers of the eye. Synthetic arginine-glycine-aspartic acid RGD peptides can bind tov3 integrins to mediate cellular uptake and blockv3 integrin function to reduce the blood flow in vascular area. So this peptide is example of targeting moieties that could be combined with nanomedicine to treat vascular endothelia cells in the cornea. However, long-term improvement in visual acuity and general long-term efficacy are unknown. Corneal NV can also be induced by inflammation. So, Kaempfero (KM), one kind of flavonoids, can be used as a bifunctional agent, not only inhibit the angiogenesis for impended the vascular formation, but also relief the inflammation in cornea. Hyuronic acid nanoparticle (HA NPs) with Kaempferol encapsulation as eyedrop for ocular drug delivery will be investigated in this project. Thus, the general goal of the current study is to investigate the bioactivity and bioavailability of nanoparticles with therapeutic agents designed to target neovascular endothelial cells in cornea for inhibit angiogenesis in it and clarify their underlying mechanisms. The working hypothesis of this proposal is that long term effects of antiangiogenesis provide by the targetable nanomedicine can effectively inhibit neovascular formation in eye to prevent cornea dysfunction. By using this newly nanomedicine, RGD grafted HA nanoparticle with KM loading, which not only provide strong interaction with cornea surface but also maintain the effective dosage in cornea. Thus, the specific aims of this 3-year proposal are: (1)To fabricate RGD peptide decorated HA nanoparticles with KM encapsulation for target vascular endothelia cells; (2) To delineate the difference of slow released nanomedicine for the anti-angiogenesis inhibition and it mechanism in vitro and (3) To elucidate the therapeutic efficiency by topical delivery (eyedrop) in a mice/rabbit model with corneal neovascular ingrowth.
|Effective start/end date||8/1/16 → 7/31/17|