Development of a novel methyl cellulose hydrogel with physiologically relevant controlled ethanol release for cervical dysplasia ablation.

Cervical cancer is a leading cause of death in women in low- and middle-income countries (LMICs) and disproportionately affects women of minority populations in the United States, primarily due to a lack of infrastructural support for specialized care. A promising treatment that meets accessibility requirements is ethyl cellulose (EC)-ethanol ablation-inducing necrotic cell death through application of ethanol to kill precancerous cells. While previous work focused on injecting EC-ethanol to ablate high-grade dysplasia (which can reach depths up to 5 mm below the tissue surface), low-grade dysplasia requires a different delivery method as it is much more superficial (reaching depths of only 1-3 mm). Here, we have developed a topical gel for local ethanol ablation of low-grade dysplasia with minimal damage to healthy cervical tissue. We investigated several gellants, including methyl cellulose (MC), EC, and Pluronic® F-127, to develop an ethanol gel that meets parameters for low cost and topical ease of use. Formulations with F-127 did not form gels with ethanol. Formulations with EC and MC were gel-forming. The MC-based formulations formed more uniform and stable gels that hold their own weight while still being spreadable at both room and body temperatures, key criteria for local cervical application. The optimal formulation contained 70% ethanol, 20% water, and 10% MC. One gram of this formulation represents approximately 5¢ material cost, and formulated gels were stable for at least 1 week when stored at 4, 22, 30, and 37°C. Additionally, the MC gel achieved localized ablation within 5 min after application to cervical cancer cells in vitro. Taken together, we have developed a low-cost, efficacious, MC-based ethanol gel fit for translational testing to treat low-grade cervical dysplasia. This gel may provide a novel treatment option for women in LMICs, without causing major side effects or loss of healthy cervical tissue.