Water Inhalable Nicotine (WIN) as An Innovative Orally Inhaled Nicotine Replacement Therapy (NRT) for Smoking Cessation

About This Grant

Project Summary Smoking, linked to severe health issues and deaths, sees low cessation rates with current therapies due to relapse. Inhaled nicotine, unlike other nicotine replacement therapies (NRT), offers better pharmacokinetics and sensory satisfaction, potentially improving quit rates. Despite growing regulatory support for innovative cessation solutions, no FDA-approved inhaled NRTs exist, revealing a significant market opportunity for new developments. Our latest innovation, Water Inhalable Nicotine (WIN), revolutionizes smoking cessation, featuring an easy-to- use, cartridge-based design for inhaled NRT. WIN utilizes a proprietary water formulation tailored for inhalation, offering rapid and effective nicotine delivery that replicates the sensory satisfaction of smoking. This system is enhanced with an intelligent dose algorithm integrated into a mobile app, supported by a color-coded step-down treatment regimen, enabling personalized cessation strategies. The design ensures minimal inhalation toxicity and environmental impact, while its precise, controlled delivery improves medication compliance and balances abuse liability, making it ideal for adult smokers and underserved populations. This innovative approach positions WIN at the forefront of smoking cessation solutions, combining user safety with environmental responsibility. In Aim 1, we will focus on optimizing WIN’s design for three nicotine strengths (High/Medium/Low) through comprehensive aerosol and chemical characterizations. We will conduct extensive aerosol testing to quantify nicotine emissions under varied conditions and analyze aerosol particle size to ensure optimal lung deposition. Additionally, assessments of harmful constituents such as carbonyls, VOCs, heavy metals, etc. will confirm WIN’s safety and efficacy, aiming for precise delivery and consistent performance. Aim 2 involves in vitro assessments to confirm the safety of WIN by testing its aerosol condensates for cytotoxicity using MTT assays on human alveolar epithelial cells (A549 cell ALI model) and for genotoxicity using Ames tests on Salmonella strains. The goal is to maintain >80% cell viability and achieve <2-fold increase in revertant colonies, aligning with scientific and regulatory benchmarks for further clinical development. Aim 3 seeks to optimize the WIN device's usability by gathering non-identifiable feedback from smokers on various prototypes through anonymous third-party interviews and simulated use scenarios. Feedback will be analyzed to refine UI elements such as mouthpiece orientation, materials, LED display, and app integration, enhancing the device’s intuitiveness and user-friendliness to improve smoking cessation outcomes. To strategically navigate the regulatory pathway, we will consult with experts and schedule a Pre-IND meeting with the FDA, ensuring our strategy aligns with regulatory standards. SBIR Phase II will involve GLP-compliant toxicity tests and a Phase 1 clinical study to assess WIN’s pharmacokinetics and safety, progressing towards FDA approval and enhancing public health by aiding smokers in quitting.