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

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-1ß (IL-1ß) 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-1ß and TNF-α. Glycerospanlastics could be promising safe ototopical nanoplatforms for OM treatment and other middle ear disorders.

Engineered triamcinolone acetonide loaded glycerosomes as a novel ear delivery system for the treatment of otitis media.

Ear-oriented therapeutics vehiculation strategies are requisites for effective treatment of various otic ailments including otitis media (OM). Conquering minimal permeability of the intrinsic barrier of middle ear; intact tympanic membrane (TM) is still a defiance. In this study, the fabrication of glycerosomes was explored to boost triamcinolone acetonide (TA) delivery to the middle ear via the otic application to improve treatment of OM. Opting a d-optimal design, TA glycerosomes were formulated and optimized using ethanol injection method. The optimized formula was assessed for morphology, viscosity, ex vivo TM permeation and deposition and physical stability. Moreover, OM induction in rats using lipopolysaccharides was conducted, histological and biochemical investigations were performed to assess the therapeutic potential of TA glycerosomes and their tolerability as well. The optimized formula displayed a nanosized value (106.1 ± 2.82), low polydispersity index (0.079 ± 0.04), satisfactory drug entrapment efficiency (80.62 ± 4.41 %), shear thinning behavior and excellent physical stability. Ex-vivo TM permeation and deposition monitoring for 24 h demonstrated greater flux and deposition compared to free drug. More importantly, the in vivo studies demonstrated the supremacy of glycerosomes with respect to tolerability and efficacy in alleviating OM following ototopical application compared to marketed drug. Such therapeutic modality represents a promising option to boost the efficacy of otic drugs, awaiting clinical translation.