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® 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-80×320) and d = 200 nm; h = 200 nm (PRINT-Doc-200×200) were compared to Docetaxel in mice bearing human ovarian carcinoma SKOV-3 flank xenografts. The Docetaxel plasma exposure was ~ 20-fold higher for both particles compared to docetaxel. Additionally, the volume of distribution (Vd) of Docetaxel in PRINT formulations was ~ 18-fold (PRINT-Doc-80×320) and ~ 33-fold (PRINT-Doc-200×200) 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 (~ 53% higher for PRINT-Doc-80×320 and ~ 76% higher for PRINT-Doc-200×200 particles). PRINT-Doc-80×320 had lower exposures in the liver, spleen and lung compared with PRINT-Doc-200×200. 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 EditorIn 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.

Graphical AbstractThe top-down particle fabrication technique Particle Replication in Non-Wetting Templates (PRINT®) was used to fabricate size and shape specific nanoparticles containing docetaxel. A size–shape dependent docetaxel distribution was observed when particles were dosed to mice bearing human ovarian carcinoma cells. The particle with the smaller diameter (d = 80 nm versus d = 200 nm) had less docetaxel distribution into the spleen, liver and lungs but higher accumulation in the tumor from 0 to 24 h.Figure optionsDownload high-quality image (418 K)Download as PowerPoint slide