Contact lenses as a drug delivery device for epidermal growth factor in the treatment of ocular wounds

Abstract

Background: This work was conducted to investigate the uptake and release of epidermal growth factor (EGF) from hydrogel contact lenses and to determine whether the released protein would be therapeutically active in a rabbit corneal epithelial defect model of ocular trauma, prior to use in humans. Methods:The uptake and release of EGF from hydrogel contact lens materials were determined by high-pressure liquid chromatography. Contact lenses composed of vasurfilcon A or lotrafilcon A (containing silicone) were incubated in a source solution containing 0.4 ppm EGF for seven hours. To determine the kinetics of drug uptake into the contact lens matrix, drug concentration in the source solution was measured at zero, one, 60, 240 and 420 minutes. To determine the kinetics of release, loaded contact lenses were immersed in a recipient solution of phosphate-buffered saline. Therapeutic activity in vivo was investigated by placing prepared lenses on the surface of abraded corneas of New Zealand White rabbits, with abraded corneas of contralateral eyes used as controls. Control eyes were treated with contact lenses placed in saline for injection. Wound closure was assessed hourly. Results: Uptake and release of EGF were demonstrated for vasurfilcon A but not lotrafilcon A contact lens materials. The retention time of EGF released from vasurfilcon A contact lenses was similar to control EGF not exposed to contact lens polymers. The greatest adsorption of EGF into the lens material occurred within approximately 120 minutes, with a flattening of the rate of uptake thereafter. Abraded eyes in rabbits showed a significantly higher overall healing rate for EGF-treated contact lenses compared with control eyes (p < 0.0001). Conclusions: EGF can be delivered from some but not all hydrogel materials. Lens materials composed of silicone may not be useful for delivering EGF to the eye. EGFtreated contact lenses may be a useful device to facilitate healing of ocular wounds.

Vitronectin: A Matrix Support Factor for Human Limbal Epithelial Progenitor Cells

“…38 Interestingly, though EGF alone induced rapid reepithelialization, the regenerating cells were loosely bound to the corneal BM, indicating the necessity for coapplication of adhesion-like molecules to facilitate stability. 39 Our system has this added potential because VN is known to couple growth factors such as insulin-like growth factor-binding proteins (IGF-BPs), which partake in corneal 48 and cutaneous 49 wound repair. VN/IGF-BP complexes are also supportive factors for cultured SCs, 50 and VN, FN, and nerve growth factor have each been found to promote the healing of persistent corneal epithelial defects.…”

“…Application of recombinant proteins could be a standardized approach for treating ocular surface disorders that do not require a cell-based therapy, including persistent epithelial defects. 37,44 -47 Indeed, CLs have been used to deliver EGF to wounded corneas, 39 and pharmacologic agents have been absorbed onto lenses for glaucoma management. 38 Interestingly, though EGF alone induced rapid reepithelialization, the regenerating cells were loosely bound to the corneal BM, indicating the necessity for coapplication of adhesion-like molecules to facilitate stability.…”

“…2A). Given that previous studies have shown the delivery of biologicals and therapeutic agents to the ocular surface by CLs, 38,39 we sought to determine whether lenses could be coated with VN. Lotrafilcon A CLs were incubated in sera from patients with LSCD for 10 days before they were placed in PBS for an additional 7 days.…”

Novel Therapy to Treat Corneal Epithelial Defects: A Hypothesis with Growth Hormone

“…This study design was partially based on previous work by Schultz et al, who showed that EGF, HGH, and dexamethasone delivered through a contact lens delivery system, could accelerate wound healing in a New Zealand white rabbit corneal debridement model. 94,95 They showed that the molecular structure of EGF and rHGH were not altered upon release from the contact lens hydrogel in the New Zealand white rabbit corneal debridement model. Such a local delivery scheme using a polymer vehicle allows a safe and sustainable release system translatable to clinical applications and is ideal for delivery of a protein.…”

Uptake and Release Phenomena in Contact Lens Care by Silicone Hydrogel Lenses

“…Over 90% of surveyed contact lens fitters expressed an interest in the development of drug-releasing contact lens materials. 5 The uptake and subsequent release of pharmaceutical agents have been the topic of much recent research, and published work has demonstrated the release of many topical drugs from commercial soft lens materials, including fluoroquinolones, 6-8 cromolyn sodium, 9 ketotifen, 9,10 ketorolac, 9 dexamethasone, 9,11 epidermal growth factor, 12 and timolol. 13 Although the release of topical therapeutic drugs from soft lenses may be advantageous for treating ocular surface disease, the uptake and subsequent release of components from disinfection systems have proven to be a negative factor.…”