Construction of therapeutic glycopeptide hydrogel as a new substitute for antiproliferative drugs to inhibit postoperative scarring formation

Abstract

A biocompatible glycopeptide comprised of an N-fluorenyl-9-methoxycarbonyl phenylalanine-phenylalanine-aspartic acid (FMOC-Phe-Phe-Asp) sequence and a therapeutic glucosamine moiety was designed and synthesized. When dissolving the glycopeptide in PBS solution (pH 7.4), a hydrogel can be formed via the self-assembly of the glycopeptide. Spectroscopic techniques indicate that the self-assembly of the glycopeptide is built on hydrogen bonding interactions between the peptide backbones and π-stacking of FMOC tails. After the administration of this therapeutic glycopeptide hydrogel in filtration surgery of rabbit eyes, due to the glucosamine moieties of the hydrogel inhibiting fibrosis, blebs and filtration fistula formed after the filtration surgery are patent without postoperative scarring formation, resulting in very low intraocular pressure (IOP) of the rabbit eyes within 21 days after surgery. In comparison with traditional antiproliferative drug injections administrated after glaucoma-filtering surgery, the intraoperative administration of this glycopeptide hydrogel can achieve an equivalent therapeutic effect. Importantly, the intraoperative administration of this therapeutic glycopeptide hydrogel has potential advantages including providing convenience and preventing the toxicity of antiproliferative drugs to the ocular tissues, presenting a significant potential alternative for the treatment of glaucoma.