Paper Number
FE22
Session
Foams, Emulsions, Surfactants, and Micelles
Title
Tuning the thermoresponsive assembly and gelation of ABA/BAB triblock polymers for targeted antibiotic delivery to treat middle ear infections
Presentation Date and Time
October 12, 2021 (Tuesday) 2:20
Track / Room
Track 3 / Meeting Room A-B
Authors
- White, Joanna M. (University of Minnesota, Chemical Engineering and Materials Science)
- Calabrese, Michelle A. (University of Minnesota, Chemical Engineering and Materials Science)
Author and Affiliation Lines
Joanna M. White and Michelle A. Calabrese
Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55414
Speaker / Presenter
White, Joanna M.
Keywords
applied rheology; gels; micelles; polymer solutions
Text of Abstract
Middle ear infections are prevalent among young children and frequently recur. The standard oral antibiotic treatment method relies heavily upon parental compliance for optimal dosing and results in systemic exposure that can have numerous adverse side-effects. To minimize these effects, we are developing a non-invasive targeted delivery system based on poloxamer 407 (P407), a commercially-available FDA-approved ABA triblock polymer, antibiotic ciprofloxacin, and three chemical permeation enhancers. The system is liquid at room temperature so that it can be syringed into the ear canal and forms a gel comprised of FCC-packed spherical micelles upon contact with the warm tympanic membrane (TM), allowing for extended antibiotic diffusion into the middle ear. Our prior work showed that chemical modification of P407, which resulted in bridged micelles, was required for effective delivery in a chinchilla model; however this compound was novel and its degradation products are of unknown toxicity, potentially impeding rapid translation of the technology into clinical practice. To avoid this complication, we have incorporated reverse poloxamers (RPs), containing the same blocks as poloxamers but organized in a BAB fashion, into the P407 formulation to induce bridging and tune the transition temperature and rheological properties of the hydrogel. At constant poloxamer content, RP addition shifts thermal disorder-to-order transition to higher temperatures regardless of RP identity, which improves the syringeability of the hydrogels. At constant P407 content, RP addition in low concentrations does not markedly change the FCC structure or mechanical properties. However, higher RP content leads to formation of both new spherical packings and ordered phases, depending on the RP hydrophobe content and molecular weight. Understanding and controlling these self-assembled structures will enable creation of antibiotic-loaded hydrogel systems with targeted gelation temperatures and optimal diffusion across the TM.