Faculty Collaboration Database

Controlled release of ciprofloxacin and ceftriaxone from a single ototopical administration of antibiotic-loaded polymer microspheres and thermoresponsive gel. PLoS One 2020;15(10):e0240535

Date

10/13/2020

Pubmed ID

33045028

Pubmed Central ID

PMC7549778

DOI

10.1371/journal.pone.0240535

Scopus ID

2-s2.0-85092466321 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

Acute otitis media (AOM) is the main indication for pediatric antibiotic prescriptions, accounting for 25% of prescriptions. While the use of topical drops can minimize the administered dose of antibiotic and adverse systemic effects compared to oral antibiotics, their use has limitations, partially due to low patient compliance, high dosing frequency, and difficulty of administration. Lack of proper treatment can lead to development of chronic OM, which may require invasive interventions. Previous studies have shown that gel-based drug delivery to the ear is possible with intratympanic injection or chemical permeation enhancers (CPEs). However, many patients are reluctant to accept invasive treatments and CPEs have demonstrated toxicity to the tympanic membrane (TM). We developed a novel method of delivering therapeutics to the TM and middle ear using a topical, thermoresponsive gel depot containing antibiotic-loaded poly(lactic-co-glycolic acid) microspheres. Our in vitro and ex vivo results suggest that the sustained presentation can safely allow therapeutically relevant drug concentrations to penetrate the TM to the middle ear for up to 14 days. Animal results indicate sufficient antibiotic released for treatment from topical administration 24h after bacterial inoculation. However, animals treated 72h after inoculation, a more clinically relevant treatment practice, displayed spontaneous clearance of infection as is also often observed in the clinic. Despite this variability in the disease model, data suggest the system can safely treat bacterial infection, with future studies necessary to optimize microsphere formulations for scaled up dosage of antibiotic as well as further investigation of the influence of spontaneous bacterial clearance and of biofilm formation on effectiveness of treatment. To our knowledge, this study represents the first truly topical drug delivery system to the middle ear without the use of CPEs.

Author List

Bruk LA, Dunkelberger KE, Khampang P, Hong W, Sadagopan S, Alper CM, Fedorchak MV

Author

Wenzhou Hong DVM, PhD Assistant Professor in the Otolaryngology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Administration, Topical
Animals
Anti-Bacterial Agents
Ceftriaxone
Chinchilla
Ciprofloxacin
Delayed-Action Preparations
Drug Carriers
Drug Compounding
Gels
Guinea Pigs
Microspheres
Otitis Media