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Hee-Kyoung Lee, Shirley Luo, Barbara M Wirostko, Brenda Mann; Carboxymethylated Hyaluronic acid (CMHA-S)-based Ocular Delivery of Antibiotics. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4119.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal ulcers, an ocular emergency and a leading cause of blindness globally, require compounded off label topical antibiotics, often at an inconvenient hourly round-the-clock multiple day administration. A topical CMHA-S biodegradable film that delivers small molecules in sustained-released formulation to overcome this challenge has been developed. Using Besifloxacin as a target drug, in vitro feasibility of the novel film product was assessed
Films were fabricated in silicone-based molds using CMHA-S and poly(ethyleneglycol) diacrylate (PEGDA) as a cross-linker. Various amounts of Besifloxacin-HCl (150, 300, 750, and 1500 μg) were formulated into the polymer solution prior to cross-linking. Polymerized CMHA-S gels were dried at room temperature overnight to create thin films. Drug release in phosphate buffered saline (PBS) was monitored by UV absorption. Released drug was calculated from the Besifloxacin standard solution. Besifloxacin-loaded films were sterilized using ethylene oxide (EtO). The efficacy against both S. aureus and P. aeruginosa was tested by Zone of Inhibition (ZOI).
Besifloxacin was released until 56 days (11, 16, 56, and 56 days for 150, 300, 750, and 1500 μg-loaded films, respectively). The monitoring was stopped when the daily released amount reached 1 μg. For all 4 films, the released amount at day 7 was greater than 10 μg, which was efficacious in ZOI studies against both S. aureus and P. aeruginosa. Efficacy was similar for both pre- and post-sterilized films.
Besifloxacin-containing CMHA-S films yielded reproducible in vitro release for up to 56 days. This film can ultimately be a commercially viable product to meet the medical needs of a single-application ocular antibiotic to avoid hourly dosing. Furthermore, this system can be expanded to deliver other molecules to treat additional ocular pathologies.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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