Executive Summary : | The proposal aims to conduct comprehensive NMR studies on fluorinated anticancer drugs using hybrid vesicles (HVs) made of liposomes and polymersomes. The focus is on characterization of HV-drug mixtures using 19F NMR, as the choice of HV is crucial for drug loading and release. The research aims to provide a molecular perspective on HV-drug mixtures, as the loading and release characteristics are determined by structural, dynamical, and transport factors. Fluorine often leads to enhanced lipid solubility and transport of drugs, while the replacement of an oxidizable C-H group by C-F benefits from enhanced metabolic activity, decreased basicity, and increased binding affinity with receptors. The wide chemical shift range of 19F (~800 ppm) will help monitor free and HV-bound drug species in the presence of HVs. The proposal will use 19F NMR, along with 1H and 31P, and advanced tools of modern NMR to characterize fluorinated anticancer drugs with HVs. This will provide complete structural, dynamical, and transport information through homo and heteronuclear nOe, high field spin-relaxation, and high field-gradient diffusometry. STD NMR and spin relaxation approaches will further characterize HV-drug mixtures. This interdisciplinary proposal aims to study and understand the fundamental structural, dynamical, and transport aspects of HV-drug systems and how these impact their drug loading and release characteristics. |