Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous

Abstract

Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature—a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye’s posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration

“…Therefore, further research is needed to precisely determine whether these differences are influenced solely by the size of the peptide or by other factors, such as concentration and flow rate [ 61 ]. Therefore, ongoing efforts in some studies focus on increasing the vitreous half-lives of drugs [ 68 , 69 ], and subsequent research is needed for peptide modifications to enhance the effects of FBP. Additionally, it is possible that another R-length FBP may be more suitable for rabbits; so, further research is needed to investigate the differences in efficacy of FBP based on R-length derivatives.…”

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives

“…Adjusting the molecule quantity of amphiphile peptide during hydrogel production can easily regulate the released dynamics of the loaded drug. At a ratio of 1:2 between ranibizumab and peptide amphiphile molecule, only 18.8% of the drug was released within 150 h, indicating significant improvement for achieving sustained release [ 63 ]. Furthermore, a tetra-armed polyethylene glycol (tetra-PEG) hydrogel has been designed to load bevacizumab.…”

Nanotechnology-based ocular drug delivery systems: recent advances and future prospects

“…One study combined nanofibers with hydrogels for intravitreal anti-VEGF drug delivery. This modulated, injectable, biodegradable hydrogel nanofiber system can change the peptide concentration to adjust the dose, providing a broad application prospect for treating wet age-related macular degeneration [ 203 ]. Likewise, a double network patch was designed by compounding electrospinning nanofibers of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by cross-linking poly with thioketal diamine and 3,3’-dithiobis.…”