Development of a thermosensitive hydrogel containing liposomes for sustained dexamethasone delivery in sensorineural hearing loss.

Dexamethasone-loaded liposomes composed of DSPC/Chol/PEG (85/10/5 mol%) and dispersed in a 16.25% Poloxamer 407 (P407) hydrogel were developed as a local therapeutic strategy for sound trauma-induced sensorineural hearing loss (SNHL). Physicochemical and rheological characterization demonstrated that the formulation remains injectable at room temperature and undergoes rapid in situ gelation within 8.0 ± 3.8 min in the middle ear cavity at 37°C. Incorporation of liposomes into the 16.25% P407 hydrogel significantly prolonged the in vitro release of encapsulated dexamethasone compared to the free drug solution. Cryogenic transmission electron microscopy (cryo-TEM) revealed multilamellar and multivesicular liposomal vesicles, consistent with sustained release behavior. The formulation was well tolerated by HEI-OC1 cells and cochlear explants and conferred a significant otoprotective effect, as evidenced by preservation of synaptic surface area following kainic acid-induced excitotoxic injury.