title: Silk hydrogels for sustained ocular delivery of anti-vascular endothelial growth factor (anti-VEGF) therapeutics.
abstract: Silk hydrogels were formulated with anti-vascular endothelial growth factor (anti-VEGF) therapeutics for sustained ocular drug delivery. Using silk fibroin as a vehicle for delivery, bevacizumab-loaded hydrogel formulations demonstrated sustained release of 3 months or greater in experiments in vitro as well as in vivo using an intravitreal injection model in Dutch-belted rabbits. Using both standard dose (1.25mg bevacizumab/50 μL injection) and high dose (5.0mg bevacizumab/50 μL injection) hydrogel formulations, release concentrations were achieved at day 90 that were equivalent or greater than those achieved at day 30 with the positive standard dose control (single injection (50 μL) of 1.25mg bevacizumab solution), which is estimated to be the therapeutic threshold based on the current dosage administration schedule of 1 injection/month. These gels also demonstrated signs of biodegradation after 3 months, suggesting that repeated injections may be possible (e.g., one injection every 3-6 months or longer). Due to its pharmacokinetic and biodegradation profiles, this delivery system may be used to reduce the frequency of dosing for patients currently enduring treatment using bevacizumab or other anti-VEGF therapeutics.
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA; Ekteino Laboratories, Waltham, MA, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Lovett
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA; Ekteino Laboratories, Waltham, MA, USA.
authors.forename: Tuna
authors.initials: T
authors.lastname: Yucel
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA.
authors.forename: Lyndsey
authors.initials: L
authors.lastname: York
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Keirstead
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Haggerty
authors.affiliation: Tufts University, Department of Biomedical Engineering, Medford, MA, USA. Electronic address: David.Kaplan@tufts.edu.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D060433:Administration, Ophthalmic; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005349:Fibroins / Q000737:chemistry*; D020100:Hydrogels; D058449:Intravitreal Injections; D011817:Rabbits; D047011:Silk / Q000737:chemistry; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D020100:Hydrogels; D047011:Silk; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D005349:Fibroins
keywords: Bevacizumab; Biodegradation; Controlled release; Hydrogel; Silk fibroin; Sustained drug delivery