Researchers Say Eyedrops Could Replace Injections for Anti-VEGF Delivery

Scientists in the United Kingdom believe they have found a way to deliver new ophthalmologic drugs in eyedrop form, potentially eliminating the need for the current injection delivery method.

The researchers say their data suggest popular anti-vascular endothelial growth factor (anti-VEGF) therapies can be safely and efficiently delivered via cell-penetrating peptides (CPPs). The research is preliminary and is based only on animal and human cell models. However, if the findings are borne out, the discovery could be a major game-changer for patients taking ranibizumab (Lucentis) and bevacizumab (Avastin) for eye conditions such as wet age-related macular degeneration.

University of Birmingham biochemist Felicity de Cogan, PhD, who led the research team, said the current injection method of drug delivery is a major hindrance for patients with vascular conditions like AMD.

“Although anti-VEGF drugs are extremely successful treatments for these vascular diseases, their repeated delivery by intravitreal (ivit) injection is very stressful to patients, costly to administer, and associated with significant complications,” wrote de Cogan and her colleagues. “...Therefore, there is an urgent and unmet need for an alternative and less invasive drug-delivery route.”

The concept of using CPPs as a drug-delivery method isn’t new, but de Cogan said it hasn’t been used to replace injections because the unique anatomy of the eye raises a host of unique challenges.

“The various layers of the cornea, conjunctiva, sclera, and retina, along with the vascular blood-aqueous and blood-retinal barriers, create formidable static obstacles to drug penetration,” de Cogan wrote. “Dynamic impediments to drug delivery include the choroidal and conjunctival blood flow, lymphatic clearance, efflux pumps, and tear dilution.”

In the past, short-sequence peptides have been used to help shepherd small-molecule therapies to retinal cells after a sub-retinal injection. However, de Cogan wanted to find out if CPPs could carry large-molecule drugs to the tissues in the back of the eye after only a topical application.

To study the question, de Cogan and colleagues looked at the efficacy of CPP delivery in the eyes of rats and pigs, and in adult human retinal pigment epithelium (RPE) and primary human fibroblast cells.

The data were clear: CPPs have high penetrating capabilities and low toxicity.

“The CPP-drug has the potential to have a significant impact on the treatment of AMD by revolutionizing drug-delivery options,” de Cogan said, in a press release.

Not only would an eyedrop formulation be easier on patients who take the drug, but de Cogan said it could also significantly reduce the cost of the drug, since administration would be much simpler. That’s an important point for payers and patients because while bevacizumab is about $50-60 per dose, ranibizumab’s price tag is close to $2,000 per dose. Another popular anti-VEGF drug, aflibercept, costs nearly as much.

In the University of Birmingham’s press release, de Cogan suggested that Britain’s National Health Service should take note of her study.

“We believe this is going to be very important in terms of empowering of patients and reducing the cost of treatment to the NHS,” she said.

The study is titled, “Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.” It was published in the May issue of Investigative Ophthalmology and Visual Science and can be read in its entirety for free at the journal’s website.

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