AntiXero: An extended duration solution for cancer-associated dry mouth.

PROJECT SUMMARY Xerostomia (XS), or chronic dry mouth, is a prevalent medical condition marked by dryness, burning, or soreness of the oral cavity, affecting about 25% of adults. Cancer patients, particularly those undergoing radiation therapy and chemotherapy, are highly susceptible to XS due to damage or removal of salivary glands. This impairment leads to difficulties in eating and drinking, exacerbating weight loss in cancer patients. XS also heightens the risk of oral health problems, such as caries and periodontal disease, affecting patients’ overall quality of life and treatment outcomes. Standard treatments for radiation-induced XS include sialogogues (e.g., pilocarpine, cevimeline), which stimulate saliva production but are associated with side effects such as sweating and nausea. Alternative treatments, including submandibular gland transfer, acupuncture-like transcutaneous electrical nerve stimulation (ALTENS), hyperbaric oxygen, and acupuncture exist, but may involve elective surgery and persistent dry mouth symptoms. Currently available oral rinses only offer short-term relief (~4 hours), and viscous formulations that exhibit extended exposure are impractical. Consequently, there is pressing need for a longer- lasting, non-toxic XS remedy to address this significant unmet need. In an effort to ameliorate this debilitating condition, AntiXero has begun development of an all-in-one hyaluronic acid (HA)-based oral rinse that provides relief from chronic dry mouth for ~24 hours. This work is predicated on our previous work in developing novel lubricant solutions for dry eye disease, as the mucinous ocular surface is highly similar to that of the oral mucosa. The objective of this proposal is thus to adapt this innovative lubricant technology first evaluated in the ocular surface to be used in patients with XS. This solution utilizes a unique boronic acid-functionalized HA anchoring chemistry that works by chemically binding to the sialic acid moieties of salivary mucins in the oral cavity to increase the retention time, which serves to enhance exposure for superior efficacy. Preliminary data suggests that the application of this proprietary solution could significantly lengthen the time that is required between rinses. This is in stark contrast to currently available rinses which require continual application, which further worsens the already demanding and burdensome quotidian daily regimen that cancer patients must overcome. The overall objective of this Phase I proposal is to synthesize and identify lead HA polymers that exhibit enhanced desiccation resilience and moisture retention properties (Aim 1), followed by further in vitro characterization as to the cytoprotective effects of lead polymer species (Aim 2). Successful completion of this Phase I project will demonstrate proof-of-concept as to the ability of an optimized HA-derivatized polymer to ameliorate chronic dry mouth, thus informing testing in clinical trials (Phase II).