Zirconyl acetaminophen phosphate: A nanoscaled analgetic with very high drug load

Abstract

Drug release belongs to the most challenging aspects of nanoparticles addressing molecular biology and medicine. Besides targeted delivery, obvious challenges are related to high drug load and continuous slow drug release. Based on our recently developed concept of inorganic-organic hybrid nanoparticles (IOH-NP), we here present [ZrO]2+[AAP]2− IOH-NPs containing the analgetic phosphate prodrug acetaminophen phosphate for drug release. [ZrO]2+[AAP]2− combines an uncomplex synthesis in water with a high prodrug load of 68wt.%. [ZrO]2+[AAP]2− nanoparticles exhibit a diameter of 37(11)nm and can be readily obtained as colloidally highly stable suspension in water. The chemical composition is studied in detail based on infrared spectroscopy, energy-dispersive X-ray analysis, thermogravimetry and elemental analysis. Moreover, the release of acetaminophen from [ZrO]2+[AAP]2− is studied by means of model experiments indicating the carbon content of the nanoparticles and, in alternative, the fluorescence of labeled nanoparticles. Both data show a continuous release of 80wt.% of the analgetic acetaminophen on a time scale up to 48h.