Delineating the usage of dexamethasone-loaded cubosomes as a therapeutic armamentarium for hearing loss versus its protective effect: In-vitro and in-vivo animal study

The evidence of significant ototoxicity during the use of cisplatin as a chemotherapeutic agent has burdened its use in cancer patients. Our aim is to entrap dexamethasone (DEX) as a protective or a therapeutic agent in a sustained release formulation (cubosomes) suitable for intratympanic administration thus improving patient quality of life. DEX cubosomes were prepared using solvent evaporation and melt dispersion-emulsification methods. The study involved the physicochemical characterization of the prepared cubosomes. The optimum formula was selected for the in-vivo study where its ability to retain hearing function was tested using distortion product otoacoustic emission (DPOAE) test. DEX cubosomes showed cubic structure with homogenous particle size distribution less than 220 nm, zeta potential between -0.070 and -6.990 mV and % entrapment efficiency ranging from 74.72% to 84.11%. Sustained release behavior of cubosomes was observed where 57.8% of DEX was released in 14 days. The DPOAE test has showed that DEX cubosomes possessed a superior effect than the marketed DEX solution. The percent recovery of hearing loss for the rats receiving DEX cubosomes as a therapy or as protectant was significantly (p < 0.05) higher than those receiving DEX solution. A histopathological study showed that prepared DEX cubosomes was safe and compatible for intratympanic injection. As a conclusion, the proposed system can be efficiently utilized to attenuate the severe ototoxicity accompanied by cisplatin administration.