September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Crosslinked carboxymethylated hyaluronic acid (CMHA-S)-based ocular sustained delivery of antibiotics
Author Affiliations & Notes
  • Hee-Kyoung Lee
    Jade Therapeutics, Salt Lake City, Utah, United States
  • Benjamin Ham
    Jade Therapeutics, Salt Lake City, Utah, United States
  • Shirley Luo
    Jade Therapeutics, Salt Lake City, Utah, United States
    University of Utah, Salt Lake City, Utah, United States
  • Brittany Coats
    University of Utah, Salt Lake City, Utah, United States
  • Nathaniel Cady
    SUNY Polytech Institute, Albany, New York, United States
  • Brenda Mann
    Jade Therapeutics, Salt Lake City, Utah, United States
  • MaryJane Rafii
    Jade Therapeutics, Salt Lake City, Utah, United States
  • Barbara M Wirostko
    Jade Therapeutics, Salt Lake City, Utah, United States
    University of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Hee-Kyoung Lee, Jade (F), Jade (E), Jade (R); Benjamin Ham, Jade (F), Jade (E); Shirley Luo, Jade (F), Jade (E), Jade (R); Brittany Coats, Jade (F); Nathaniel Cady, Jade (F); Brenda Mann, Jade (F), Jade (E); MaryJane Rafii, Jade (F), Jade (P); Barbara Wirostko, Jade (F), Jade (R)
  • Footnotes
    Support  NSF SBIR Phase II 1430921
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1124. doi:
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    • Get Citation

      Hee-Kyoung Lee, Benjamin Ham, Shirley Luo, Brittany Coats, Nathaniel Cady, Brenda Mann, MaryJane Rafii, Barbara M Wirostko; Crosslinked carboxymethylated hyaluronic acid (CMHA-S)-based ocular sustained delivery of antibiotics. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1124.

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

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Abstract

Purpose : Corneal ulcers, an ocular emergency and a leading cause of blindness globally, require compounded off-label topical antibiotics and/or approved fluoroquinolones at a very inconvenient hourly round-the-clock multiple day administration to prevent corneal vision loss. Jade Therapeutics is developing a topical hydrogel/hyaluronic acid (CMHA-S) biodegradable film to deliver small molecules in sustained-released (SR) formulation to overcome hourly dosing challenges. Jade developed the molding procedure for manufacturing precise/reproducible films, and assessed the in vitro feasibility of this novel ocular film product.

Methods : The film shape was designed in three different geometries to yield films with different cross-sectional shapes. CMHA-S films were fabricated in poly-dimethylsiloxane (PDMS)-based molds using proprietary thiolated carboxymethylated HA and poly(ethyleneglycol) diacrylate (PEGDA), as a cross-linker. Moxifloxacin-HCl, Moxifloxacin-free base, Vancomycin, and Besifloxacin-HCl were formulated into the liquid polymer solution prior to cross-linking. Polymerized CMHA-S gel was dried at 37 °C overnight to create thin clear and pliable films. Drug release was monitored in phosphate buffered saline (PBS) by UV absorption. Released drug amount was calculated from the standard solution.

Results : Mold preparation was optimized to enable better molding and the release of the films from the molds. The functional molding procedure was established to produce a variety of film shapes and sizes. The films were successfully fabricated with all 4 drugs. The drug release resulted in burst within 1-2 days with Moxifloxacin-HCl, Moxifloxacin-free base, and Vancomycin. Besifloxacin, however, was continuously released through Day 6 (for 75 μg Besifloxacin, 1 μg release at Day 6) and Day 11 (150 μg Besifloxacin, 1 μg release at Day 11). The accumulated released drug was close to 100%.

Conclusions : Besifloxacin-containing HA films yielded reproducible sustained in vitro release for 6-11 days. This film can ultimately lead to a commercially viable product to meet the medical needs of a single-application antibiotic to the eye to avoid hourly dosing. Furthermore, this system can be expanded to deliver other antimicrobials to treat other indications such as ophthalmic fungal or viral infections.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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