Corneal Penetrating Elastin-Like Polypeptide Carriers

Abstract

Purpose: 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 mg/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.

A kidney-selective biopolymer for targeted drug delivery

“…In contrast, Tat-ELP was toxic to HGME cells. This is consistent with previous findings that Tat-ELP exhibits cell line-dependent cytotoxicity in several cell types (19,33).…”

Thermally-Responsive Loading and Release of Elastin-Like Polypeptides from Contact Lenses

“…The delivery of therapeutic ELP fusion proteins to the ocular system and its compatibility, biodistribution, or therapeutic efficacy were studied by us and other groups. Examples include the delivery of intravitreal αB crystallin ELP fusion to a mouse model of age-related macular degeneration [43], topical lacritin-ELP as an eyedrop for healing of mouse corneal wound model [44], intravitreal injection of poly(VPAVG) particles to a normal rabbit model [45], and cell-penetrating peptide ELP fusions to a normal rabbit model [46]. As these modalities have shown ELPs as a highly promising ocular drug delivery platform, it is necessary to have a unique set of evidence that the delivery of ELPs or ELP fusions can be rerouted to the ocular system via contact lenses in a more hassle-free fashion.…”

Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide

“…Our study aimed to elucidate how molecular weight impacts pharmacokinetics, biodistribution and renal localization of the macromolecular therapeutic carrier, ELP. ELPs have been utilized in the past two decades for tumor targeted drug delivery 5 , 25 , 29 , for generation of slow-release subcutaneous drug depots 7 , 22 , 30 , for ocular drug delivery 10 , 31 , and to prevent placental drug transfer 8 , 32 along with many other applications. Original work with ELPs was done in the cancer drug delivery field, and their tumor accumulation has been investigated extensively 5 , 15 , 25 , 29 .…”