Sodium Hyaluronate Based Drug Delivery to the Outer and Inner Ear

Abstract

We have developed two projects using sodium hyaluronate (HA)-based systems for drug delivery to the ear. First, we investigated an HA-based hydrogel for use as a single use antibiotic treatment for otitis externa. Otitis externa, also known as outer ear infection, is a frequent affliction in both humans and animals. The most prevalent treatment for otitis externa is ear drops, but it is difficult to adhere properly to this treatment, causing poor patient compliance and the potential for complications. As a result, we have developed an HA-based hydrogel for use as a single application treatment for otitis externa to increase ease of use and improve patient outcomes. Herein, we studied the manufacturability, applicability, and shelf life of the hydrogels. We found that the hydrogels have a robust and scalable manufacturing process, have multiple supply chain options, and have a wide tolerance for pH adjustment and HA concentration, simplifying the manufacturing process. We also found that the hydrogels are highly appliable for use as a single application therapeutic for otitis externa. They are capable of loading and releasing a wide variety of model drugs, and alternative loading strategies can be utilized to alter the release profiles. The hydrogels are not skin irritants, and drug release from the hydrogels is not impacted by physiologically relevant factors. Finally, we investigated the shelf life of the hydrogels, and found that the shelf life of the hydrogels is impacted by both HA concentration and molecular weight. Additionally, we are currently developing topically applied treatments for hearing loss based on HA. In this work, we investigated the impact of HA molecular weight on permeation through in vitro models of the tympanic and round window membranes. We found that HA with a lower molecular weight has higher permeability through both membranes. Additionally, we found that the round window membrane has much higher HA permeability than the tympanic membrane