Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft

The particle fabrication technique PRINT (R) was used to fabricate monodisperse size and shape specific poly(lactide-co-glycolide) particles loaded with the chemotherapeutic Docetaxel. The pharmacokinetics of two cylindrical shaped particles with diameter=80 nm; height=320 nm (PRINT-Doc-80x320) and d=200 nm; h=200 nm (PRINT-Doc-200x200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was similar to 20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was similar to 18-fold (PRINT-Doc-80x320) and similar to 33-fold (PRINT-Doc-200x200) lower than Docetaxel. The prolonged duration of Docetaxel in plasma when dosed with PRINT formulations subsequently led to increased tumor exposure of Docetaxel from 0 to 168 h (similar to 53% higher for PRINT-Doc-80x320 and similar to 76% higher for PRINT-Doc-200x200 particles). PRINT-Doc-80x320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200x200. Thus, the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. From the Clinical Editor: In this study, the plasma, tumor, and tissue pharmacokinetics of different Docetaxel nanoparticles of precise shape and size were characterized in mice with human ovarian carcinoma xenograft. It is concluded that the use of particles with smaller feature size may be preferred to decrease clearance by organs of the mononuclear phagocyte system. (C) 2013 Elsevier Inc. All rights reserved.