Synthesis and evaluation of lung retentive prodrugs

Inhalation is an increasingly important delivery approach for therapeutic agents to the lung. The proposed project seeks to generate a new platform technology to prepare novel pH-triggered lung tissue-retentive prodrugs to deliver therapeutics in a more efficacious and safe manner and involves chemically linking a set of drug molecules to lung tissue-retentive groups, generating a set of prodrugs that become activated through a novel pH-sensitive linking group. The main objectives for this project lie in synthetic organic chemistry with the design and synthesis of conjugate prodrugs that are activated at pH >6.5, the pH of the lung surface environment, to release the drug over a time course of up to 12-24 hours; coupled with the establishment of analytical methods to measure the decomposition of the prodrugs over the experimental time course.