The new gel eye drops can treat corneal neovascular diseases

Corneal neovascularization is a blinding mechanism of ophthalmic diseases that seriously affects vision, which can be seen in corneal inflammation, trauma, bacterial, fungal and viral infections, etc., with a global incidence of 4.1%-10.4%, eventually leading to blindness in 12%-57.4% of patients. At present, the disease mainly includes drug treatment and corneal transplantation, but there are problems such as low drug absorption, large side effects, difficult and expensive surgery, scarcity of corneal materials, and postoperative recurrence.

Corneal neovascular disease is characterized by abnormal growth of blood vessels within corneal tissue, of which vascular endothelial growth factor (VEGF) is one of the most critical regulators. Therefore, anti-VEGF drugs (such as aflibercept) that have been clinically proven to be safe and effective are highly feasible for the treatment of corneal neovascular diseases. However, as the first line of defense of the eye, the cornea’s natural defense functions such as blinking, tear washing, ocular surface tissue barrier, etc. can effectively protect it from foreign foreign body invasion, but at the same time, it also seriously hinders the delivery of macromolecular drugs such as aflibercept to the eye, and how to non-invasively let the drug cross the ocular surface barrier to exert its efficacy is the key to the treatment of the disease.

The reporter learned from the research group of Shi Junfeng, professor of the Interdisciplinary Institute of Life Medicine of Hunan University, on September 23, that the research group and the research group of Li Yun, professor of ophthalmology at the Second Xiangya Hospital of Central South University, developed an aflibercept ophthalmic gel preparation with cell membrane peptide as the delivery medium. Among them, cell perforator peptides are similar to Trojan horses, which can effectively help large molecules such as aflibercept penetrate into corneal tissues to exert their efficacy and play a role in the treatment of corneal neovascular diseases.

During the experiment, the gel preparation prepared by the team was added dropwise to treat corneal neovascular disease.

The team used the cell membrane peptide to wrap aflibercept to form a permeable complex, and then combined the complex with the peptide gel to make a gel preparation. The gel preparation can resist tear washout, effectively prolong the residence time of the drug in the cornea, so as to deliver aflibercept to the cornea that is difficult to penetrate the tissue, and truly achieve non-invasive transmembrane administration.

“We found that the gel delivery system can effectively penetrate mouse corneal epithelial cells and enter the corneal stroma to exert its efficacy. This result is highly dependent on the ternary complex formed by the transmembrane peptide, peptide gel, and drug, because the binary mixture of the perforating peptide plus the drug is almost impermeable to the cornea. Shi Junfeng said. In the rabbit eye corneal neovascularization model, the gel eye drops can effectively prevent the development of rabbit eye corneal neovascularization, significantly reduce the density of corneal neovascularization, and have no obvious toxic reaction. However, the simple aflibercept eye drop group had no obvious therapeutic effect compared with the ordinary normal saline group.

The experimenters used gel preparations for rabbit corneal neovascularization treatment (the first from the right is Li Yun).

According to reports, this achievement is the first to study the possibility of cell perforation peptide-mediated macromolecular anti-VEGF drugs to treat corneal neovascular diseases, which provides a good paradigm for the treatment of ocular neovascular diseases. At present, the drug delivery system has applied for an invention patent, and it is planned to carry out further clinical translational research.

The team conducts experiments. (All images in this article are provided by interviewees)

The above results were recently published in the journal Small, and the research has been supported by the National Natural Science Foundation of China, the Natural Science Foundation of Hunan Province, the Natural Science Foundation of Changsha Municipality, the Shenzhen Science and Technology Development Fund, and the Hunan Provincial Health Commission. (Source: Wang Haohao, China Science News)

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