Thermoresponsive microspears may minimize surgical infections

June 28, 2018
Michelle Dalton, ELS
Michelle Dalton, ELS

Endophthalmitis may be a rare occurrence, but it can be a devastating one. Acute cases are known to be caused by gram-positive bacteria and usually present within 6 weeks post-surgery. Chronic cases can occur beyond the 6-week timetable, but are often related to a previous surgery and the culprit is often a progressive infection (e.g., fungus).

Acute cases should be treated as an emergency (and may result in treatment with vitrectomy if presenting vision is poor enough). If vision has not yet been adversely impacted, treatment may only require antibiotics or antifungal agents.

Preventing endophthalmitis, therefore, has often been the goal for surgeons, and patients are typically prescribed an antibiotic prophylaxis regimen prior to undergoing surgery.

But most antibiotic prophylaxis regimens are comprised of multiple doses, meaning “patient compliance is always a concern, especially for older patients who may have difficulty in instilling the drops,” said Eric Romanowski, MS (The Charles T. Campbell Ophthalmic Microbiology Laboratory, University of Pittsburgh).

To overcome that obstacle and eliminate the patient adherence issue, one potential solution has been to provide a noninvasive depot of antibiotic that can be released over time to replace the multiple doses of antibiotic.

At the University of Pittsburgh, however, engineers have developed a thermoresponsive, hydrogel-controlled release drug containing microspheres, or SoliDrop.

Rabbit studies

SoliDrop is liquid at room temperature, but “forms a comfortable, pliable, formfitting nondegradable hydrogel after exposure to body temperature in conjunctival cul-de-sac,” he said. The hydrogel material “is loaded with controlled-release microspheres capable of delivering a wide range of drugs for varying lengths.”

Preliminary rabbit studies using SoliDrop with glaucoma drug brimonidine demonstrated good efficacy over 28 days. The goals of the latest study were to evaluate the efficacy of the drug-delivery system and its ability to release moxifloxacin at a high concentration over a short period.

“We wanted to provide a proof of principle that the placement of a single drop of moxifloxacin controlled release hydrogel drop into the conjunctival cul-de-sac can provide effective prophylaxis against bacterial endophthalmitis in a rabbit model,” Romanowski said.

Leaving Morgan V. Fedorchak, PhD (developer of the technology) to “do her magic,” Romanowski said she was able to develop microspheres that have “a quick burst release over 60 minutes, and while there were other microspheres that will allow a release over 7 days.”

There were eight rabbits in each of three groups: a moxifloxacin microsphere group, a blank hydrogel group, and a control group that was instilled with 10 drops of moxifloxacin over 24 hours; they then injected Staphylococcus aureus into the anterior chamber.

Researchers began instilling moxifloxacin starting an hour before inoculation, every 15 minutes, then again right before inoculation and once after inoculation, and four more times post-inoculation over 24 hours. The hydrogel depot was placed 60 minutes before inoculation.

At 24 hours post-injection, the researchers performed a slit lamp exam, and then cultured the aqueous and vitreous for bacterial strains. Both the hydrogel implant and the control moxifloxacin eyes had no evidence of endophthalmitis.

The blank hydrogel eyes, however, all developed endophthalmitis. Further clinical studies are needed to confirm these initial results, Romanowski said.

Disclosures:

Eric Romanowski, MSE: e.romanowskie@upmc.edu 
This article was adapted from Romanowski’s AAO 2017 presentation. He has no financial disclosures.