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Corneal Penetrating Elastin-Like Polypeptide Carriers.

Authors
  • George, Eric M1, 2
  • Mahdi, Fakhri3
  • Logue, Omar C3
  • Robinson, Grant G3
  • Bidwell, Gene L 3rd2, 3
  • 1 1 Department of Physiology and Biophysics, University of Mississippi Medical Center , Jackson, Mississippi.
  • 2 2 Department of Biochemistry, University of Mississippi Medical Center , Jackson, Mississippi.
  • 3 3 Department of Neurology University of Mississippi Medical Center , Jackson, Mississippi.
Type
Published Article
Journal
Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
Publication Date
Apr 01, 2016
Volume
32
Issue
3
Pages
163–171
Identifiers
DOI: 10.1089/jop.2015.0082
PMID: 26672799
Source
Medline
Language
English
License
Unknown

Abstract

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. 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. 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. 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.

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