Freeze-dried diethylenetriaminepentaacetic acid-functionalized polymeric micelles containing paclitaxel: A kit formulation for theranostic application in cancer

Abstract Polymeric micelles (PM) are versatile nanoparticles with suitable properties to tumor delivery of hydrophobic drugs such as paclitaxel (PTX) and imaging probes such as technetium-99 m. However, instability of drug content in aqueous medium and obstacles related to lengthy radiolabeling procedures, high radiation exposure and risk of human error limit its clinical application. Freeze-dried kit formulation might be a strategy to overcome these issues. Thus, we developed a freeze-dried kit formulation containing diethylenetriaminepentaacetic acid (DTPA)-functionalized 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] polymeric micelles carrying PTX (PM-DTPA/PTX) for application in the diagnosis and/or treatment of solid tumors. PM-DTPA/PTX were prepared and the physical and radiochemical characteristics (size, zeta potential, PTX content and radiolabeling yields) evaluated before lyophilization process and after storage up to 180 days. In vivo biodistribution studies were performed in 4T1 breast tumor-bearing BALB/c mice. A freeze-dried kit containing PM-DTPA/PTX showed high storage stability in all parameters evaluate up to 180 days since no significant alteration was observed at all evaluated timeframes. The freeze-drying process did not change the physicochemical and biological properties of the PM, including the property of tumor targeting. Therefore, a stable freeze-dried kit containing PM-DTPA/PTX was developed as an easy and fast preparation and showed high potential for theranostic application in cancer treatment.