Abstract
In this study, we developed injectable intratympanic hyaluronic acid (HA) depots for the treatment of hearing loss. We prepared an injectable click-crosslinking formulation by modifying HA with tetrazine (HA-TET) and trans-cyclooctene (HA-TCO), which crosslinked to form an HA depot (Cx-HA). Preparation of the click-crosslinking HA formulation was facile, and Cx-HA depot formation was reproducible. Additionally, the Cx-HA hydrogel was significantly stiffer than HA hydrogel. To monitor the degradation pattern of hydrogels, we mixed a zwitterionic near-infrared (NIR) fluorophore (e.g., ZW800-1C) in the click-crosslinking HA formulation. Then, HA-TET and HA-TCO solutions containing ZW800-1C were loaded separately into the compartments of a dual-barrel syringe for intratympanic injection. The Cx-HA depots formed quickly, and an extended residence time in the tympanic cavity was confirmed by performing NIR fluorescence imaging. We have successfully prepared an injectable click-crosslinking HA formulation that has promise as an intratympanic drug depot.
Highlights
Partial or complete hearing loss can be caused by inner ear disease, aging, exposure to toxins, noise, or Meniere’s disease, which may result in sudden hearing loss [1]
Our findings will facilitate the efficient development of click-crosslinking hyaluronic acid (HA) hydrogel formulations for drug delivery via intratympanic injection to address unmet needs for the treatment of hearing loss
Injectable click-crosslinking NIR-fluorescent HA formulation (HA-TET and HA-TCO with NIRfluorescent) and the Cx-HA depot with NIR-fluorescent obtained by injecting the formulation
Summary
Partial or complete hearing loss can be caused by inner ear disease, aging, exposure to toxins, noise, or Meniere’s disease, which may result in sudden hearing loss [1]. Injection research of hydrogels that could form our depots in situhave to achieve a high steroid the concentration the Several teams, including group, recently reported results ofatinjecting location responsible for hearing loss. Our group and other research teams have developed systems to utilize the biorthogonal and HA-TCO are mixed, they form a crosslinked HA (Cx-HA) depot This technique has the click-crosslinking Diels–Alder reaction between tetrazine (TET) and trans-cyclooctene (TCO), advantages of facile handling and reproducibility, and the residence times of Cx-HA depots are because the reaction proceeds rapidly under physiological conditions [19,20,21,22]. Our findings will facilitate the efficient development of click-crosslinking HA hydrogel formulations for drug delivery via intratympanic injection to address unmet needs for the treatment of hearing loss
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