Topical Delivery of Elastic Liposomal Vesicles for Treatment of Middle and Inner Ear Diseases

Abstract

We present a topical drug delivery mechanism through the ear canal to the middle and inner ear using liposomal nanoparticles without disrupting the integrity of the tympanic membrane. The current delivery method provides a noninvasive and safer alternative to transtympanic membrane injections, ear tubes followed by ear drops administration, and systemic drug formulations. We investigate the capability of liposomal NPs, particularly transfersomes (TLipo), used as drug delivery vesicles to penetrate the tympanic membrane (TM) and round window membrane (RWM) with high affinity, specificity, and retention time. The TLipo is applied to the ear canal and found to pass through the tympanic membrane quickly in 3 h post drug administration. They are identified in the middle ear cavity 6 h and in the inner ear 24 h after drug administration. We performed cytotoxicity in vitro and ototoxicity in vivo studies. Cell viability shows no significant difference between the applied TLipo concentration and control. Furthermore, auditory brainstem response (ABR) reveals no hearing loss in 1 week and 1 month post-administration. Immunohistochemistry results demonstrate no evidence of hair cell loss in the cochlea at 1 month following TLipo administration. Together, the data suggested that TLipo can be used as a vehicle for topical drug delivery to the middle ear and inner ear.

Cutting‐Edge Achievements of Inner Ear Drug Delivery Systems

“…In a recent study, Kashfi Sadaba et al synthesized transfersomes by lipid membrane hydration. [ 12 ] Fluorescent signals of the drugs were observed in the middle and inner ear cavities, vascular striae, and Corti organ at 6 and 24 h after administration, respectively, and transfersomes were eliminated from the ear after 1 month of treatment ( Figure 2 a). Small extracellular vesicles (sEVs) released from most cells are a type of lipid vesicle containing proteins, nucleic acids, and metabolites, showing neuroprotective and immunomodulatory effects on their precursor cells.…”

“…Scale bars are ii) 20 μm and iii) 600 μm. Reproduced with permission [12]. Copyright 2022, American Chemical Society.…”

Elastic Liposomes Containing Calcium/Magnesium Ferrite Nanoparticles Coupled with Gold Nanorods for Application in Photothermal Therapy

“…Abs (diluted AuNRs solution) − Abs (uncoupled AuNRs) Abs (diluted AuNRs solution) × diluted AuNRs solution mass (5) For accurate evaluation of the morphology and size distribution of magnetic and plasmonic NPs and of the coupling between them, a TEM characterization was performed. The obtained images are presented in Figure 3.…”

“…Considering the treatment of skin diseases, which represent one of the most frequent types of disorders all over the world [ 3 ], liposomes must be designed to ensure high penetration into the different layers of the skin, especially into its barrier, the stratum corneum (SC). For that purpose, elastic liposomes (ELs) are an excellent approach for topical applications due to their ultra-deformable properties [ 4 , 5 , 6 ]. Generally, ELs consist of an aqueous core surrounded by a double bilayer of phospholipids and single chain surfactants with a high radius of curvature, also known as edge activators (EAs) [ 1 , 7 ].…”