Controlled-release of epidermal growth factor from cationized gelatin hydrogel enhances corneal epithelial wound healing.
We designed a new ophthalmic drug-delivery system for epidermal growth factor (EGF) from the biodegradable hydrogel of cationized gelatin. We placed a cationized gelatin hydrogel (CGH) with incorporated (125)I-labelled EGF in the conjunctival sac of mice and measured the residual radioactivity at different times to evaluate the in vivo profile of EGF release. Approximately 60-67% and 10-12% of EGF applied initially remained 1 and 7 days after application, respectively; whereas EGF delivered in topically applied solution or via EGF impregnation of soft contact lenses disappeared within the first day. We also placed CGH films with 5.0 mug of incorporated EGF on round corneal defects in rabbits to evaluate the healing process using image analysis software and to assess epithelial proliferation immunohistochemically by counting the number of Ki67-positive cells. The application of a CGH film with incorporated EGF resulted in a reduction in the epithelial defect in rabbit corneas accompanied by significantly enhanced epithelial proliferation compared with the reduction seen after the topical application of EGF solution or the placement of an EGF-free CGH film. The controlled release of EGF from a CGH placed over a corneal epithelial defect accelerated ocular surface wound healing.
Hori
Kuniko
K
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Hirokoji, Kawaramachi, Kamigyoku, Kyoto 602-0841, Japan. khori@ophth.kpu-m.ac.jp
Sotozono
Chie
C
Hamuro
Junji
J
Yamasaki
Kenta
K
Kimura
Yu
Y
Ozeki
Makoto
M
Tabata
Yasuhiko
Y
Kinoshita
Shigeru
S
D000818:Animals; D002412:Cations; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003228:Conjunctiva / Q000378:metabolism; D003316:Corneal Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005780:Gelatin / Q000737:chemistry* / Q000378:metabolism; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D020100:Hydrogels; D051379:Mice; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D002412:Cations; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D005780:Gelatin; D005976:Glutaral