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A corneal penetrating drug delivery system based on elastin‐like polypeptide (1053.4)
Author(s) -
Bidwell Gene,
Liu Huiling,
Robinson Grant,
Marquart Mary,
George Eric
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1053.4
Subject(s) - drug delivery , corneal neovascularization , corneal epithelium , cornea , stromal cell , elastin , chemistry , medicine , pharmacology , neovascularization , ophthalmology , cancer research , pathology , angiogenesis , organic chemistry
The corneal epithelium is connected by tight junctions and serves as a protective layer, but its resistance to penetration also presents a challenge to drug delivery. Upon injury, the cornea is susceptible to infection and/or neovascularization (NV), both of which can threaten sight. In the case of corneal bacterial infection, delivery of antibiotics and the development of antibiotic resistance are significant hurdles to effective therapy. In the case of corneal NV, there are no good treatments beyond removal of the insulting agent and resting of the eye. The goal of this study was to generate an effective and non‐toxic protein‐based delivery system for targeting therapeutic agents through the corneal epithelium. This drug delivery system utilized a biopolymer called elastin‐like polypeptide (ELP), an engineered protein that is easily purified and easily modified to carry drugs or therapeutic proteins. To facilitate delivery to the corneal stroma, we fused cell penetrating peptides (CPPs) to ELP. Addition of CPPs enhanced the total uptake and retention of ELP as much as 3‐fold in healthy rabbit corneas and in a rabbit burn model of corneal NV. The CPP also mediated penetration of ELP beyond the epithelium and basal lamina into the stromal layer. Our results demonstrate that CPP‐ELPs are a powerful platform for corneal drug delivery, and we describe their use for delivery of antibacterial and antiangiogenic agents. Grant Funding Source : Supported by an Intramural grant to GLB from U of MS Med Center and NIH grant 1K99HL116774‐01 to EMG