Evaluation of membrane-retentive pro-drugs to increase duration of effect to enable once-a-day dosing of inhaled muscarinic M3 receptor antagonists

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Inhalation is an increasingly important delivery approach of therapeutic agents to the lung. There remains an unmet medical, commercial and practical need for 'once-a-day' treatment in various therapeutic areas and this is lacking for some current therapies. Once daily treatment is possible in some cases, but this approach can involve over-dosing to give the required duration of action. A negative issue is often side-effects due to initial higher than desired drug exposure. The proposed project involves chemically modifying current drugs via a pro-drug approach. The active drug will be released in a controlled manner at the target site, so the duration of pharmacological effect will be significantly longer than the traditional approach. The concept will be tested pre-clinically with the iterative design and synthesis of various test agents and drug metabolism tests in vitro and in vivo to prove that the required extension of duration is realised.