Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and their use for bioimaging

Abstract

Li-Wen Chang,1 Mei-Ling Hou,1 Shuo-Hui Hung,2 Lie-Chwen Lin,3 Tung-Hu Tsai1,4–6 1Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, 2Department of Surgery, 3National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, 4Department of Education and Research, Taipei City Hospital, 5School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 6Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan Abstract: Bubble formulations have both diagnostic and therapeutic applications. However, research on nanobubbles/nanodroplets remains in the initial stages. In this study, a nanodroplet formulation was prepared and loaded with a novel class of chemotherapeutic drug, ie, quercetin, to observe its pharmacokinetic properties and ultrasonic bioimaging of specific sites, namely the abdominal vein and bladder. Four parallel groups were designed to investigate the effects of ultrasound and nanodroplets on the pharmacokinetics of quercetin. These groups were quercetin alone, quercetin triggered with ultrasound, quercetin-encapsulated in nanodroplets, and quercetin encapsulated in nanodroplets triggered with ultrasound. Spherical vesicles with a mean diameter of 280 nm were formed, and quercetin was completely encapsulated within. In vivo ultrasonic imaging confirmed that the nanodroplets could be treated by ultrasound. The results indicate that the initial 5-minute serum concentration, area under the concentration–time curve, elimination half-life, and clearance of quercetin were significantly enhanced by nanodroplets with or without ultrasound. Keywords: nanodroplets, quercetin, ultrasonic pharmacokinetics, ultrasonic imaging, ultrasound