title: Corneal Penetrating Elastin-Like Polypeptide Carriers.
abstract: OBJECTIVE
  Elastin-like polypeptide (ELP) is a bioengineered protein widely applied as a drug carrier due to its biocompatibility and amenability to modification with cell-penetrating peptides (CPPs) and therapeutic agents. The purpose of this study was to determine whether topically applied ELP or CPP-fused ELPs penetrate the corneal barrier.
  
  
  METHODS
  In vitro binding and cytotoxicity to human corneal epithelial (HCE) cells were determined for ELP or CPP-ELPs. Corneal binding, clearance, and penetration were assessed in a rabbit model following topical application of the fluorescently labeled proteins by quantitative fluorescence imaging and histology.
  
  
  RESULTS
  ELP bound to HCE cells in vitro, and binding/uptake was enhanced 2- to 3-fold by the addition of CPPs. When applied topically to rabbit eyes, ELP accumulated in the cornea at levels 7.4-fold higher than did an equivalent dose of immunoglobulin G. Both ELP and a CPP-ELP penetrated the corneal epithelium and were detectable in the stroma. Addition of CPPs to ELP, however, did not significantly enhance corneal uptake or penetration in vivo relative to ELP alone. The polypeptides cleared from the cornea over a period of 20-30 min after application, after which cornea levels reached a steady state of 15-30 μg/mL for up to 3 h.
  
  
  CONCLUSIONS
  The ELP drug carrier can penetrate the corneal epithelium and accumulate in the stroma. Given its amenability for fusion to multiple types of therapeutic agents, ELP has the potential to serve as a drug carrier for topical ocular applications.
authors.affiliation: 1 Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.|2 Department of Biochemistry, University of Mississippi Medical Center , Jackson, Mississippi.
authors.forename: Eric M
authors.initials: EM
authors.lastname: George
authors.affiliation: 3 Department of Neurology University of Mississippi Medical Center , Jackson, Mississippi.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Mahdi
authors.affiliation: 3 Department of Neurology University of Mississippi Medical Center , Jackson, Mississippi.
authors.forename: Omar C
authors.initials: OC
authors.lastname: Logue
authors.affiliation: 3 Department of Neurology University of Mississippi Medical Center , Jackson, Mississippi.
authors.forename: Grant G
authors.initials: GG
authors.lastname: Robinson
authors.affiliation: 2 Department of Biochemistry, University of Mississippi Medical Center , Jackson, Mississippi.|3 Department of Neurology University of Mississippi Medical Center , Jackson, Mississippi.
authors.forename: Gene L
authors.initials: GL
authors.lastname: Bidwell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004549:Elastin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008856:Microscopy, Fluorescence; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D004549:Elastin