Novel Method of Delivering Therapeutics to the Tympanic Membrane and Middle Ear Without Chemical Permeation Enhancers

December 14, 2020

UPMC Department of Otolaryngology faculty Cuneyt M. Alper, MD, recently published his research on the PLGA MS/thermoresponsive gel system in PLoS One.

The study, entitled “Controlled Release of Ciprofloxacin and Ceftriaxone from a Single Ototopical Administration of Antibiotic-loaded Polymer Microspheres and Thermoresponsive Gel,” demonstrates that the PLGA MS/thermoresponsive gel system is capable of encapsulating and subsequently releasing up to 14 days of potentially therapeutically relevant levels of two different antibiotics for clearance of bacteria present in acute otitis media.

In vitro cell viability and bacteria killing studies indicate these materials can be safe for in vivo and eventual clinical use while maintaining ability to clear bacteria. Auditory brainstem responses indicate complete coverage of TM and ability to increase volume of material applied with minimal effect on quality of life due to hearing attenuation during treatment.

In vivo studies in a chinchilla disease model demonstrate potential for the novel drug delivery system to effectively treat bacterial infection, with future studies focusing on further microsphere optimization and improvement of the disease model, including increased antibiotic delivery and accounting for variability in the model.

Histopathological evaluation indicates in vivo safety of the drug delivery system, with further analysis needed to determine material-specific toxicity as variability in the disease model is addressed. Future studies will also investigate incorporation of analgesic into the gel for local pain relief due to AOM and encapsulation of other therapeutics into this drug delivery system for topical treatment of other otic conditions, in addition to expanded testing of long-term ototoxicity.

Learn more about Dr. Alper’s study here

Reference

Bruk LA, Dunkelberger KE, Khampang P, Hong W, Sadagopan S, Alper CM, Fedorchak MV. Controlled release of ciprofloxacin and ceftriaxone from a single ototopical administration of antibiotic-loaded polymer microspheres and thermoresponsive gel. PLoS One. 2020 Oct 12;15(10):e0240535. doi: 10.1371/journal.pone.0240535. PMID: 33045028; PMCID: PMC7549778.