The present invention provides compositions and methods for delivery of therapeutic agents across an barrier. The compositions include a therapeutic agent (e.g., antimicrobial agent, antibiotic, or anesthetic agent), a permeation enhancer which increases the flux of the therapeutic agent across the barrier, and a matrix forming agent. The matrix forming agent forms a gel at a suitable gelation temperature and has rheological properties for use in drug delivery, and in some cases, the gelation temperature and rheological properties are not significantly changed from those of the composition without the permeation enhancer. The invention also provides a matrix forming agent and compositions thereof. Such compositions are particularly useful in the treatment of infectious disease (e.g., otitis media). Methods of treatment, methods of delivery, and kits for the compositions described herein are also provided.