Abstract: Liposome-based mucus-penetrating particles (MPP) capable of loading hydrophilic agents including therapeutic, prophylactic and diagnostic agents such as the diaCEST MRI contrast agent barbituric acid (BA) were evaluated to determine how to optimize delivery. Polyethylene glycol (PEG)-coated liposomes containing ?7 mol % PEG diffused only approximately 10-fold slower in human cervicovaginal mucus (CVM) compared to their theoretical speeds in water. 7 mol %-PEG liposomes provided improved vaginal distribution compared to 0 and 3 mol %-PEG liposomes.

Abstract: The present invention includes drug-loaded, polymer nanoparticles and liposomes further incorporating a non-paramagnetic, bioorganic CEST agent. The CEST agent allows for an alternative approach to accomplish MR-compatible in vivo tracking of drug-loaded polymer nanoparticles and liposomes, including simultaneous multi-color mapping of more than one particle type, or of the same particle type delivered via two different routes (e.g., systemic versus local). Additionally, the present invention can include a library of biodegradable diamagnetic (DIA)CEST agents. These DIACEST agents can be incorporated into nanoparticle-based delivery systems, such as stealth liposomes loaded with doxorubicin and stealth polymer nanoparticles loaded with paclitaxel. These systems can be tracked, according to an embodiment of the present invention using CEST-based MRI (compared to SPECT/CT) as a method to monitor the efficiency with which the nanoparticles reach the targeted tumors and how long they persist.