Biopolymer Lipid Hybrid Microcarrier for Transmembrane Inner Ear Delivery of Dexamethasone

Abstract

Dexamethasone is one of the most often used corticosteroid drugs for sensorineural hearing loss treatment, and is used either by intratympanic injection or through systemic delivery. In this study, a biopolymer lipid hybrid microcarrier was investigated for enhanced local drug delivery and sustained release at the round window membrane level of the middle ear for the treatment of sensorineural hearing loss (SNHL). Dexamethasone-loaded and dexamethasone-free microparticles were prepared using biopolymers (polysaccharide and protein, pectin and bovine serum albumin, respectively) combined with lipid components (phosphatidylcholine and Dimethyldioctadecylammonium bromide) in order to obtain a biopolymer–liposome hybrid system, with a complex structure combining to enhance performance in terms of physical and chemical stability. The structure of the microparticles was evaluated by FTIR, XRD, thermal analysis, optical microscopy, and scanning electron microscopy (SEM). The encapsulation efficiency determination and the in vitro Dexamethasone release study were performed using UV-Vis spectroscopy. The high value of encapsulation efficiency and the results of the release study indicated six days of sustained release, encouraging us to evaluate the in vitro cytotoxicity of Dexamethasone-loaded microparticles and their influence on the cytotoxicity induced by Cisplatin on auditory HEI-OC1 cells. The results show that the new particles are able to protect the inner ear sensory cells.

Microfluidic Preparation of Gelatin Methacryloyl Microgels as Local Drug Delivery Vehicles for Hearing Loss Therapy

“…Microgels are microsized polymer particles of macromolecular networks with compartmentalization ability and selective permeability, which are favorable for the encapsulation and release of drug agents. Although microparticles have been exploited in middle ear drug delivery in several studies, their biocompatibility, morphology, and adhesion can be further improved. , Numerous technologies, such as spray drying, emulsification solvent evaporation, and microfluidics, are employed to microparticle syntheses. , In particular, microfluidic technology is excellent in manipulating small amounts of fluids at the microscale, and thus, it is capable of generating microparticles with finely controlled sizes and structures. , To date, numerous studies on microfluidic-derived microparticles for use as vehicles in oral delivery, wound healing, antitumor treatments, etc., have been carried out, − whereas their applications in otic treatments have been less explored . Considering the issues associated with intratympanic delivery, the component, size, and physicochemical properties of the microgels must be carefully selected to maintain sustained drug release and overcome the obstacle to air conduction of sound .…”

“…Although microparticles have been exploited in middle ear drug delivery in several studies, their biocompatibility, morphology, and adhesion can be further improved. 18,19 Numerous technologies, such as spray drying, emulsification solvent evaporation, and microfluidics, are employed to microparticle syntheses. 20,21 In particular, microfluidic technology is excellent in manipulating small amounts of fluids at the microscale, and thus, it is capable of generating microparticles with finely controlled sizes and structures.…”