Glycerospanlastics: State-of-the-art two-in-one nano-vesicles for boosting ear drug delivery in otitis media treatment

Abstract

The purpose of this research was to design innovative nanovesicles for ototopical conveyance of triamcinolone acetonide (TA) for otitis media (OM) treatment via incorporating glycerol into nanospanlastics to be termed "Glycerospanlastics". The glycerospanlastics were formulated employing ethanol injection procedure, and central composite design (CCD) was harnessed for optimization of the vesicles. Various attributes of the nanovesicles, viz. particle size distribution, surface charge, TA entrapment efficiency, morphology as well as ex-vivo permeation across the tympanic membrane (TM) were characterized. In vivo implementation of the optimized glycerospanlastics loaded with TA was appraised in OM-induced rats via histopathological and biochemical measurements of the tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) levels in ear homogenates. The safety and tolerability of optimized TA glycerospanlastics was also investigated in non-OM induced animals. The results demonstrated that the optimized TA-glycerospanlastics were in a nanometer range (around 200 nm) with negative charges, high TA entrapment (>85%), good storage properties and better TM permeation relative to TA suspension. More importantly, TA-glycerospanlastics performed better than marketed drug suspension in OM treatment as manifested by restoration of histopathological alterations in TM and lowered values of IL-1β and TNF-α. Glycerospanlastics could be promising safe ototopical nanoplatforms for OM treatment and other middle ear disorders.

Keywords: Ear; Ear delivery; Glycerospanlastics; Otitis media; Triamcinolone acetonide; Tympanic membrane.