Prolonged Local Melatonin Delivery for Recurrent Laryngeal Nerve Neuropraxia

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Project Summary/Abstract: This application requests a career development award for a head and neck surgeon with an interest in recurrent laryngeal nerve neuropraxia and developing prolonged methods of topical therapeutic delivery. The described career development plan will help her to build the skills in data analysis, study design, and drug delivery necessary to become an independent translational researcher developing topical therapeutics for Otolaryngology applications. The candidate’s mentorship team combines expertise from neuroscience, bioengineering, laryngology, and otolaryngology to provide a collaborative environment to help her accomplish her goals. Dr. Kita’s objectives during this mentored career development award will be: 1) Complete coursework in biostatistical methods, 2) Develop expertise in sustained-release therapeutics, and 3) Design a method of further characterizing recovery from neuropraxia in a Long Evans rat model. Manipulation of the recurrent laryngeal nerve is common in surgical procedures of the neck. Postoperative weakness can results in difficulty with speech, swallowing, and breathing. Return of function from neuropraxia, the mildest and most common form of nerve injury, often takes a few months. The impairment in communication, swallowing ability, and breathing that results can severely impact patient quality of life during this time. This award will allow the candidate to study recovery from neuropraxia and screen topical interventions for their ability to expedite recovery. Through the completion of this award, Dr. Kita will establish preliminary data and a model of neuropraxia that may be used to test therapeutics. This will be accomplished in 3 aims: 1. Design a drug-eluting hydrogel with sustained elution. Melatonin will be encapsulated in poly (lactic-co- glycolic acid) microparticles within fibrin hydrogels and elution of medication characterized. 2. Determine Schwann cell response to melatonin in vitro. Schwann cells will be grown with resuspended melatonin, filter-sterilized eluted melatonin, and with melatonin secreted from microparticles in hydrogels. 3. Create a rat model for characterizing recovery from recurrent laryngeal nerve after neuropraxia. Vocal fold movement video, electromyography readings, ultrasonography, and immunohistochemistry will be used to describe recovery after injury in a Long-Evans rat model. Drug-eluting hydrogels will be implanted and analyzed for their ability to shorten the period to recovery of vocal fold motion seen on ultrasonography. Recurrent laryngeal nerve neuropraxia is a common and debilitating complication after surgeries in the neck. Better characterization of this injury will allow insight into ways to help at risk individuals. Through this award the candidate will investigate a method of prolonged topical therapeutic delivery for its ability to assist in recovery of vocal fold function after surgical manipulation and establish the skills necessary to become an independent translational researcher.