Insight into the in vivo fate of intravenous herpetrione amorphous nanosuspensions by aggregation-caused quenching probes

Intravenous nanosuspensions are attracted growing attention as a viable strategy for development of intravenous formulations of poorly water-soluble drugs. However, only few information about the biological fate of intravenous nanosuspensions is currently known, especially amorphous nanosuspensions are not reported yet. In this study, the in vivo fate of herpetrione (HPE) amorphous nanosuspensions following intravenous administration was explored by using an aggregation-caused quenching (ACQ) probe and HPLC methods. The ACQ probe is physically embedded into HPE nanoparticles via anti-solvent method to form HPE hybrid nanosuspensions (HPE-HNSs) for bioimaging. HPE-HNSs emit strong and stable fluorescence, but fluorescence quenches immediately upon the dissolution of HPE-HNSs, confirming the self-discrimination of HPE-HNSs. Following intravenous administration of HPE-HNSs, integral HPE-HNSs and HPE show similar degradation and biodistribution, with rapid clearance from blood circulation and obvious accumulation in liver and lung. Due to the slower dissolution and enhanced recognition by reticulo-endothelial system, 450 nm HPE-HNSs accumulate more in liver, lung and spleen than that of 200 nm HPE-HNSs. These results demonstrate that integral HPE-HNSs determine the in vivo performance of HPE-HNSs. This study provides insight into the in vivo fate of intravenous amorphous nanosuspensions.