title: Plasma, tumor and tissue pharmacokinetics of Docetaxel delivered via nanoparticles of different sizes and shapes in mice bearing SKOV-3 human ovarian carcinoma xenograft.
abstract: 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=80nm; height=320nm (PRINT-Doc-80×320) and d=200nm; h=200nm (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 168h (~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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Pharmaceutical Sciences, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Chu
authors.forename: Warefta
authors.initials: W
authors.lastname: Hasan
authors.forename: Sumit
authors.initials: S
authors.lastname: Rawal
authors.forename: Mark D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Enlow
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.forename: Arlene S
authors.initials: AS
authors.lastname: Bridges
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kuijer
authors.forename: Mary E
authors.initials: ME
authors.lastname: Napier
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D043823:Taxoids / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D043823:Taxoids; D000077143:Docetaxel