June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Hystem, a bio-absorbable protein delivery polymer: safety, tolerability and efficacy in a rabbit corneal debridement model
Author Affiliations & Notes
  • MaryJane Rafii
    Ophthalmics, Jade Therapeutics, Salt Lake City, UT
  • Barbara Wirostko
    Ophthalmics, Jade Therapeutics, Salt Lake City, UT
    Ophthalmology, University of Utah, SLC, UT
  • Liliana Werner
    Ophthalmology, University of Utah, SLC, UT
  • Nick Mamalis
    Ophthalmology, University of Utah, SLC, UT
  • Thomas Zarembinski
    BioTime, Almeda, CA
  • Stacy Pritt
    Absorption Systems, SD, CA
  • Glenwood Gum
    Absorption Systems, SD, CA
  • Footnotes
    Commercial Relationships MaryJane Rafii, Jade Therapeutics (P), Jade Therapeutics (S), Jade Therapeutics (I), Pfizer Inc. (C), Regenron (C); Barbara Wirostko, Jade Therapeutics (P), Jade Therapeutics (I), Jade Therapeutics (E), Altheos Inc. (C), Merck (C), SKS Ocular (C), USTAR (F); Liliana Werner, Aaren Scientific (F), Abbott Medical Optics (F), Advanced Vision Science (F), Alcon Laboratories (F), Anew Optics (F), Bausch & Lomb Surgical (F), Calhoun Vision (F), Innovia (F), MRI Research (C), Powervision (C), Rayner Intraocular Lenses (F), Visiogen (C); Nick Mamalis, Abbott Medical Optics (F), Alcon Laboratories, Inc (F), Allergan (F), Anew (C), Bausch & Lomb (F), Calhoun Vision, Inc (F), NuViiew, Inc (F), OpticaMedica (C), Powervision (F); Thomas Zarembinski, BioTime, Inc. (E); Stacy Pritt, Jade Therapeutics (E), Absorption Systems (E), Amakem (E); Glenwood Gum, Jade Therapeutics (F)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5048. doi:
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      MaryJane Rafii, Barbara Wirostko, Liliana Werner, Nick Mamalis, Thomas Zarembinski, Stacy Pritt, Glenwood Gum; Hystem, a bio-absorbable protein delivery polymer: safety, tolerability and efficacy in a rabbit corneal debridement model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5048.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: HyStemTM (BioTime, CA), a biodegradable hyaluronic acid (HA)-based polymer shown to promote wound healing, can be used for local, ocular sustained delivery of proteins. Safety, tolerability, and efficacy of this polymer, alone and in combination with recombinant human growth hormone (rhGH) to accelerate wound healing, was evaluated in a rabbit corneal debridement model (CDM). rhGH was selected based on its ability to activate growth factors, e.g., Insulin-like Growth Factor and Epidermal Growth Factor, that have been shown to be involved in corneal re-epithelialization.

Methods: To assess the tolerability of HyStem cross-linked with glutathione (GSSG); non-cross-linked HyStem, HyStem/GSSG, and Ringers lactate (RL) (control) were applied four times a day (QID) for 4 days topically in a CDM using New Zealand rabbits (NZR)( N=3, 2 eyes/arm). Twice daily, slit lamp exams with photos were employed to evaluate healing. Tissues were harvested on day 5 and histopathology was performed. To evaluate the efficacy of HyStem/GSSG/rhGH in accelerating wound healing, a validated NZR CDM model (N=11) was used. All 22 eyes received topical dexamethasone (dex) QID for 7 days, alone (control; n=8 eyes), with HyStem/GSSG BID (n=4 eyes), or with HyStem/GSSG/rhGH BID (4 μg/50 μL drop; n=10 eyes). Healing was assessed via daily slit lamp photos. Tissues were harvested on day 7 and histopathology was performed. Time to complete healing and daily % healing were compared across groups.

Results: Tolerability study revealed that HyStem and HyStem/GSSG were well tolerated, with a trend for faster return to normal histology vs. RL. In the efficacy study, HyStem/GSSG and HyStem/GSSG/rhGH yielded excellent safety and tolerability: histopathology was normal, with no inflammation or angiogenesis. In spite of the small sample size, an efficacy trend was seen with a faster rate to complete defect closure in the HyStem/GSSG/rhGH group as early as Day 5. By Day 6, 80% of eyes with HyStem/GSSG/rhGH were completely healed vs. 50% of HyStem/GSSG vs. 38% of dex alone.

Conclusions: HyStem can deliver, rhGH, such that an efficacy signal for faster corneal wound healing is demonstrated. HyStem and Hystem/GSSG/rhGH were well tolerated in vivo, with normal histopathology. HyStem is a viable polymer to deliver proteins, e.g., rhGH, for corneal defects that have impaired healing.

Keywords: 482 cornea: epithelium • 765 wound healing  
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