Levofloxacin-encapsulated engineered elastosomes for targeted trans-tympanic delivery: comprehensive evaluation across in vitro, microbiological, ex vivo, and in vivo models.

AIM: This study aimed to develop and optimise Levofloxacin-Encapsulated Engineered Elastosomes (LEEE) as a non-invasive nanocarrier to improve trans-tympanic drug delivery and therapeutic efficacy in acute otitis media (AOM). METHODS: LEEE were formulated using cholesterol, surfactant, edge activator, and terpene via thin-film hydration and optimised with a 2³ factorial design. Vesicles were characterised for particle size, zeta potential, entrapment efficiency, rheology, morphology, ex-vivo permeation, confocal laser scanning microscopy, antibacterial activity, biofilm inhibition, and in-vivo histopathology. RESULTS: The optimised LEEE (desirability = 0.980) exhibited a mean particle size of 100.41 ± 3.39 nm, entrapment efficiency of 86.11 ± 3.41%w/w, and zeta potential of -24.75 ± 5.02 mV. Morphology revealed uniform spherical vesicles, and rheological studies confirmed pseudoplastic behaviour. The formulation showed biphasic sustained release, enhanced tympanic membrane penetration, strong antibacterial and anti-biofilm activity, and excellent biocompatibility. CONCLUSIONS: LEEE represent a safe and effective non-invasive nanoplatform with potential to enhance drug delivery and therapeutic outcomes in AOM.